<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01729494</url>
  </required_header>
  <id_info>
    <org_study_id>BEST</org_study_id>
    <nct_id>NCT01729494</nct_id>
  </id_info>
  <brief_title>Belatacept Early Steroid Withdrawal Trial</brief_title>
  <official_title>Randomized, Open Label, Multicenter Study of Belatacept-based Early Steroid Withdrawal Regimen With Alemtuzumab or rATG Induction Compared to Tacrolimus-based Early Steroid Withdrawal Regimen With rATG Induction in Renal Transplantation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Cincinnati</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The study purpose is to determine the safety and efficacy of a belatacept-based&#xD;
      immunosuppressive regimen (calcineurin inhibitor free) with alemtuzumab or rabbit&#xD;
      antithymocyte globulin (rATG) induction and early glucocorticoid withdrawal (CSWD) and a&#xD;
      belatacept-based immunosuppressive regimen with tacrolimus-based regimen with rabbit&#xD;
      antithymocyte globulin induction and early glucocorticoid withdrawal in renal transplant&#xD;
      recipients.&#xD;
&#xD;
      The hypothesis is that a belatacept-based immunosuppressive regimen with alemtuzumab&#xD;
      induction, mycophenolate mofetil (MMF)/mycophenolic acid (MPA), and early glucocorticoid&#xD;
      withdrawal (Group A) in renal transplant recipients or Belatacept-based immunosuppressive&#xD;
      regimen with rabbit antithymocyte globulin induction, MMF/MPA and early glucocorticoid&#xD;
      withdrawal (Group B) will lead to less risk of graft loss, patient death, or reduced renal&#xD;
      function at 12 months as compared to a tacrolimus-based immunosuppressive regimen with rabbit&#xD;
      antithymocyte globulin, MMF/MPA, and early glucocorticoid withdrawal in renal transplant&#xD;
      recipients (Group C).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Renal transplant is the most effective treatment for end-stage renal disease. It provides&#xD;
      improved survival and quality of life. Maintenance of a functioning renal transplant mandates&#xD;
      lifelong immunosuppressive therapy to prevent immune destruction of the graft. Current&#xD;
      immunosuppressive regimens yield 1-year survival rates of 89% for cadaveric and 94% for&#xD;
      living-donor grafts. Over time, however, there is progressive loss of both subjects and&#xD;
      grafts. Five-year graft survival for cadaveric and living related donor renal transplants is&#xD;
      67% and 80%, respectively.&#xD;
&#xD;
      The most common causes of long-term subject and graft loss in kidney transplant recipients&#xD;
      are cardiovascular disease and chronic allograft nephropathy (CAN), respectively.&#xD;
      Paradoxically, the principal immunosuppressive therapies for renal transplant, the&#xD;
      calcineurin inhibitors (CNIs), cyclosporine (CsA) and tacrolimus, directly contribute to&#xD;
      long-term allograft loss and subject death, since they are inherently nephrotoxic and can&#xD;
      cause or exacerbate cardiovascular risks including hypertension, hypercholesterolemia, and&#xD;
      diabetes mellitus.&#xD;
&#xD;
      There is, therefore, a substantial unmet medical need for new therapies in renal transplant&#xD;
      that can provide short-term subject and graft survival comparable to the CNIs without their&#xD;
      long-term nephrotoxic, cardiovascular, and metabolic effects. Because belatacept can be&#xD;
      administered at the time of engraftment rather than in a delayed fashion, as is frequently&#xD;
      necessary with CNIs - especially in those allografts with initial impaired renal function--&#xD;
      it affords immunosuppression in a timely manner. Unlike CNIs, the targeted mechanism of&#xD;
      action of belatacept should provide immunosuppression without nephrotoxicity or adverse&#xD;
      effects on the cardiovascular/metabolic profile.&#xD;
&#xD;
      Glucocorticoids have been a cornerstone of immunosuppressive therapy for six decades.&#xD;
      Although glucocorticoids provide potent suppression of allo-immune responses in humans, their&#xD;
      adverse effects including infection, diabetes, weight gain, hypertension, hyperlipidemia,&#xD;
      bone disease, dermal thinning, collagen loss in multiple tissues, and cataracts, combined&#xD;
      with a lack of available therapeutic monitoring all argue against their continued use in&#xD;
      transplantation.&#xD;
&#xD;
      Belatacept represents a potential new treatment option for renal transplant recipients, which&#xD;
      addresses the current unmet need for an immunosuppressive treatment that provides short-term&#xD;
      outcomes comparable to calcineurin inhibitors (CNIs) with the potential to avoid their renal,&#xD;
      cardiovascular, and metabolic toxicities. However, the initial Phase 3 studies exhibited in&#xD;
      higher rate of acute rejection and malignancy. The malignancies were associated with&#xD;
      recipients who were EBV negative at the time of transplant. All EBV negative patients are&#xD;
      precluded from treatment with Belatacept. Due to the limitations of Phase 3 trial designs and&#xD;
      the required use of basilixumab induction, it is intuitive that the addition of a potent t&#xD;
      cell depleting induction agent may decrease the overall acute rejection rate in patients&#xD;
      treated with belatacept.&#xD;
&#xD;
      The current study tests these assumptions with the following immunosuppressive regimens.&#xD;
      Group A and B consist of potent T-cell depleting induction agents combined with belatacept.&#xD;
      Group C represents the most common immunosuppressive regimen currently utilized in the United&#xD;
      States. Each of these regimens include early withdrawal of glucocorticoids along with&#xD;
      maintenance mycophenolate mofetil.&#xD;
&#xD;
      Based upon the totality of available evidence, the current study offers a favorable&#xD;
      benefit/risk profile to study subjects, and the potential to continue to provide important&#xD;
      data for the development of new immunosuppressive regimens that address important unmet&#xD;
      needs.&#xD;
&#xD;
      The proposed Phase 4 study is designed to determine whether belatacept, in combination with&#xD;
      other immunosuppressive agents (rabbit antithymocyte globulin or alemtuzumab, mycophenolate&#xD;
      mofetil/EC mycophenolate sodium), may provide acceptable efficacy and safety in de novo&#xD;
      kidney transplant recipients, in a regimen that provides simultaneous CNI freedom and early&#xD;
      CSWD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Actual">December 2019</completion_date>
  <primary_completion_date type="Actual">December 2018</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure># Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR &lt; 45ml/Min</measure>
    <time_frame>12 months</time_frame>
    <description>Number of Patients that experienced patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) &lt; 45 mL/min</description>
  </primary_outcome>
  <secondary_outcome>
    <measure># Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss)</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patient who experienced Graft loss, not including (censored) patients who lost graft due to death</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure># Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR &lt; 45ml/Min at 24 Months</measure>
    <time_frame>24 months</time_frame>
    <description>Composite Endpoint of number of patients who experienced either patient death, allograft loss, or had an eGFR &lt; 45 ml/min/1.73m2</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eGFR (MRDRD) &lt; 45 ml/Min/1.73m2</measure>
    <time_frame>24 months</time_frame>
    <description>Patients with reduced Renal function measured by estimated GFR MDRD &lt; 45 ml/min at 24 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biopsy Proven Acute Rejection</measure>
    <time_frame>24 months</time_frame>
    <description>Incidence of all biopsy proven acute rejection whether clinically relevant or clinically silent.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biopsy Proven Acute Cellular Rejection</measure>
    <time_frame>24 months</time_frame>
    <description>Biopsy proven acute cellular rejection (BPACR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biopsy Proven Acute Antibody Mediated Rejection</measure>
    <time_frame>24 months</time_frame>
    <description>Incidence of patients experiencing a Biopsy proven acute antibody mediated rejection (BPAMR)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biopsy Proven Mixed Acute Rejection</measure>
    <time_frame>24 months</time_frame>
    <description>Incidence of patients experiencing a Biopsy proven acute cellular rejection with either DSA positive or C4d staining positive indicating antibody rejection</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure># of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients (%) with development of denovo DSA after transplant</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean eGFR (MDRD) (ml/Min/1.73m2)</measure>
    <time_frame>24 months</time_frame>
    <description>Mean eGFR (MDRD) (ml/min/1.73m2) measured for all patients reaching 2 year endpoint</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proteinuria UPC Ratio &gt; 0.8</measure>
    <time_frame>24 months</time_frame>
    <description>Number of Patients with a Urine protein/creatinine (UPC) ratio &gt; 0.8</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Patient Death</measure>
    <time_frame>24 months</time_frame>
    <description>Number of Patients who experienced death, all causes</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR)</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients requiring anti-lymphocyte therapy for the treatment of BPAR rejection</description>
  </other_outcome>
  <other_outcome>
    <measure>New Onset Diabetes After Transplantation (NODAT)</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients developing New Onset Diabetes Mellitus after Transplant by one of 5 definitions; only patients without preexisting diabetes were included</description>
  </other_outcome>
  <other_outcome>
    <measure>Time to First BPAR</measure>
    <time_frame>24 months</time_frame>
    <description>Mean Time to first episode of BPAR (days)</description>
  </other_outcome>
  <other_outcome>
    <measure># Patients Experiencing a First Biopsy-proven ACR With Severity Banff &gt; or = 2a Grade</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients with their First BPACR with a Banff grade &gt;= Banff 2a using the Banff 2007 classification system for biopsy grading. Banff grade 2a and above is considered severe cellular rejection and includes grades of Banff 2a, Banff 2b, and Banff 3.</description>
  </other_outcome>
  <other_outcome>
    <measure>Delayed Graft Function</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients experiencing Delayed graft function (DGF) within first week after transplant. DGF is defined as need for dialysis within the first week after transplant.</description>
  </other_outcome>
  <other_outcome>
    <measure>Leukopenia (WBC &lt; 2000/mm3)</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients developing leukopenia defined as WBC &lt; 2000/mm3</description>
  </other_outcome>
  <other_outcome>
    <measure>Steroid Therapy</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients on treatment with corticosteroids at 2 years</description>
  </other_outcome>
  <other_outcome>
    <measure>Discontinuation of Mycophenolate</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients who were discontinued from mycophenolate treatment at 2 years</description>
  </other_outcome>
  <other_outcome>
    <measure>Discontinuation of Study Treatment (Belatacept or Tacrolimus)</measure>
    <time_frame>24 months</time_frame>
    <description>Number of patients who had to Discontinue study treatment (belatacept or tacrolimus) at 2 years</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">316</enrollment>
  <condition>Renal Transplantation</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Alemtuzumab</intervention_name>
    <description>Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.</description>
    <arm_group_label>Group A</arm_group_label>
    <other_name>Campath</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>rabbit antithymocyte globulin</intervention_name>
    <description>Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.</description>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_label>Group C</arm_group_label>
    <other_name>Thymoglobulin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Belatacept</intervention_name>
    <description>Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is defined as the day of transplant.</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
    <other_name>Nulojix</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Tacrolimus</intervention_name>
    <description>Tacrolimus will be administered orally twice daily (BID). The recommended total initial dose of tacrolimus is 0.1 mg/kg/day in two divided doses orally. Tacrolimus should be started post-transplant within 48 hours or when serum creatinine drops lower than 4mg/dL, whichever comes first. The initial targeted trough level of tacrolimus will be 8 - 12 ng/mL for Days 1 through 30, with dose reduction to achieve a 12-hour trough target of 5 - 10 ng/mL thereafter.</description>
    <arm_group_label>Group C</arm_group_label>
    <other_name>Prograf, various</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate mofetil</intervention_name>
    <description>The first dose of mycophenolate mofetil/EC mycophenolate sodium will be administered pre-operatively. Patients receiving mycophenolate mofetil will be dosed 1000 mg twice daily (2000mg/day). Patients receiving EC mycophenolate sodium will be dosed 720 mg twice daily (1440 mg/day). Dose may be increased for African American transplant recipients to mycophenolate mofetil 1500 mg twice daily (3000mg/day) or EC mycophenolate sodium 1080 mg twice daily (2160 mg/day).</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_label>Group C</arm_group_label>
    <other_name>Cellcept, various, Myfortic</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>early cessation of steroids</intervention_name>
    <description>Glucocorticoid therapy will be administered as described. Methylprednisolone will be administered on Days 1 through 3. Additional tapering doses of glucocorticoids will continue to be given until Day 5 as below:&#xD;
Day 1 (day of transplant): 500mg IV prior to alemtuzumab (Group A) or rabbit antithymocyte globulin (Groups B and C) Day 2: 250mg IV Day 3: 125mg IV Day 4: 80mg p.o. Day 5: 60mg p.o. No further steroids</description>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_label>Group C</arm_group_label>
    <other_name>prednisone, various</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male and female patients &gt; 18 years of age.&#xD;
&#xD;
          2. Patient who is receiving a renal transplant from a living or deceased donor.&#xD;
&#xD;
          3. Female patients of child bearing potential must have a negative urine or serum&#xD;
             pregnancy test within the past 48 hours prior to study inclusion.&#xD;
&#xD;
          4. The patient has given written informed consent to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient has previously received an organ transplant other than a kidney.&#xD;
&#xD;
          2. Patient is receiving an human leucocyte antigen (HLA) identical living donor&#xD;
             transplant.&#xD;
&#xD;
          3. Patient who is a recipient of a multiple organ transplant.&#xD;
&#xD;
          4. Patient has a most recent cytotoxic panel reactive antibody (PRA) of &gt;25% or&#xD;
             calculated PRA of &gt; 50% where multiple moderate level HLA antibodies exist and in the&#xD;
             opinion of the PI represents substantial HLA sensitization.&#xD;
&#xD;
          5. Patient with a positive T or B cell crossmatch that is primarily due to HLA&#xD;
             antibodies.&#xD;
&#xD;
          6. Patient with a donor specific antibody (DSA) as deemed by the local PI to be&#xD;
             associated with significant risk of rejection.&#xD;
&#xD;
          7. Patient has received a blood group (ABO) incompatible donor kidney.&#xD;
&#xD;
          8. The donor and/or donor kidney meet any of the following extended criteria for organ&#xD;
             donation (ECD):&#xD;
&#xD;
               -  Donor age &gt;/= 60 years OR&#xD;
&#xD;
               -  Donor age 50-59 years and 1 of the following:&#xD;
&#xD;
                    -  Cerebrovascular accident (CVA) + hypertension + serum creatinine (SCr) &gt; 1.5&#xD;
                       mg/dL OR&#xD;
&#xD;
                    -  CVA + hypertension OR&#xD;
&#xD;
                    -  CVA + SCr &gt; 1.5 mg/dL OR&#xD;
&#xD;
                    -  Hypertension + SCr &gt; 1.5 mg/dL OR&#xD;
&#xD;
               -  Cold ischemia time (CIT) &gt; 24 hours, donor age &gt; 10 years OR&#xD;
&#xD;
               -  Donation after cardiac death (DCD)&#xD;
&#xD;
          9. Recipients will be receiving a dual or en bloc kidney transplant.&#xD;
&#xD;
         10. Donor anticipated cold ischemia is &gt; 30 hours.&#xD;
&#xD;
         11. Recipient that is seropositive for hepatitis C virus (HCV) with detectable Hepatitis C&#xD;
             viral load are excluded. HCV seropositive patients with a negative HCV viral load&#xD;
             testing may be included.&#xD;
&#xD;
         12. Recipients who are Hepatitis B core antibody seropositive are eligible if their&#xD;
             hepatitis B viral loads are negative. After transplant, their hepatitis B viral loads&#xD;
             will be monitored every three months for the first year after transplant. If hepatitis&#xD;
             B viral loads become positive, patients will be treated per institutional standard of&#xD;
             care.&#xD;
&#xD;
         13. Patients who are Hepatitis B surface antibody seropositive and who receive a kidney&#xD;
             from a Hepatitis B core surface antibody positive donor may be included.&#xD;
&#xD;
         14. Recipient or donor is known to be seropositive for human immunodeficiency virus (HIV).&#xD;
&#xD;
         15. Recipient who is seronegative for Epstein Barr virus (EBV).&#xD;
&#xD;
         16. Patient has uncontrolled concomitant infection or any other unstable medical condition&#xD;
             that could interfere with the study objectives.&#xD;
&#xD;
         17. Patients with thrombocytopenia (PLT &lt; 75,000/mm3), and/or leucopoenia (WBC &lt;&#xD;
             2,000/mm3), or anemia (hemoglobin &lt; 6 g/dL) prior to study inclusion.&#xD;
&#xD;
         18. Patient is taking or has been taking an investigational drug in the 30 days prior to&#xD;
             transplant.&#xD;
&#xD;
         19. Patient who has undergone desensitization therapy within 6 months prior to transplant.&#xD;
&#xD;
         20. Patient has a known hypersensitivity to belatacept, tacrolimus, mycophenolate mofetil,&#xD;
             alemtuzumab, rabbit anti-thymocyte globulin, or glucocorticoids.&#xD;
&#xD;
         21. Patient is receiving chronic steroid therapy at the time of transplant.&#xD;
&#xD;
         22. Patients with a history of cancer (other than non-melanoma skin cell cancers cured by&#xD;
             local resection) within the last 5 years, unless they have an expected disease free&#xD;
             survival of &gt; 95%.&#xD;
&#xD;
         23. Patient is pregnant, where pregnancy is defined as the state of a female after&#xD;
             conception and until the termination of gestation, confirmed by positive human&#xD;
             Chorionic Gonadotropin (hCG) laboratory test.&#xD;
&#xD;
         24. Women of childbearing potential must use reliable contraception simultaneously, unless&#xD;
             they are status post bilateral tubal ligation, bilateral oophorectomy, or&#xD;
             hysterectomy.&#xD;
&#xD;
         25. Patient has any form of substance abuse, psychiatric disorder or a condition that, in&#xD;
             the opinion of the investigator, may invalidate communication with the investigator.&#xD;
&#xD;
         26. Inability to cooperate or communicate with the investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>E. Steve Woodle, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>California Pacific Medical Center</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Colorado Denver</name>
      <address>
        <city>Denver</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tampa General Hospital</name>
      <address>
        <city>Tampa</city>
        <state>Florida</state>
        <zip>33606</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Illinois Medical Center at Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Minnesota</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Christ Hospital</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45219</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Wisconsin-Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53792</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>October 10, 2012</study_first_submitted>
  <study_first_submitted_qc>November 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 20, 2012</study_first_posted>
  <results_first_submitted>August 27, 2020</results_first_submitted>
  <results_first_submitted_qc>July 8, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">July 28, 2021</results_first_posted>
  <last_update_submitted>July 8, 2021</last_update_submitted>
  <last_update_submitted_qc>July 8, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Cincinnati</investigator_affiliation>
    <investigator_full_name>E. Steve Woodle</investigator_full_name>
    <investigator_title>MD, FACS</investigator_title>
  </responsible_party>
  <keyword>belatacept</keyword>
  <keyword>rabbit antithymocyte globulin</keyword>
  <keyword>alemtuzumab</keyword>
  <keyword>corticosteroid withdrawal</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Prednisone</mesh_term>
    <mesh_term>Alemtuzumab</mesh_term>
    <mesh_term>Abatacept</mesh_term>
    <mesh_term>Tacrolimus</mesh_term>
    <mesh_term>Thymoglobulin</mesh_term>
    <mesh_term>Antilymphocyte Serum</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>May 20, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/94/NCT01729494/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Group A</title>
          <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
        </group>
        <group group_id="P2">
          <title>Group B</title>
          <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label.</description>
        </group>
        <group group_id="P3">
          <title>Group C</title>
          <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="107"/>
                <participants group_id="P2" count="104"/>
                <participants group_id="P3" count="105"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="97"/>
                <participants group_id="P2" count="93"/>
                <participants group_id="P3" count="94"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="11"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Group A</title>
          <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
        </group>
        <group group_id="B2">
          <title>Group B</title>
          <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
        </group>
        <group group_id="B3">
          <title>Group C</title>
          <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="107"/>
            <count group_id="B2" value="104"/>
            <count group_id="B3" value="105"/>
            <count group_id="B4" value="316"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="51.1" spread="13.1"/>
                    <measurement group_id="B2" value="51.6" spread="11.7"/>
                    <measurement group_id="B3" value="51.5" spread="12.3"/>
                    <measurement group_id="B4" value="51.4" spread="12.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="30"/>
                    <measurement group_id="B2" value="38"/>
                    <measurement group_id="B3" value="36"/>
                    <measurement group_id="B4" value="104"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="77"/>
                    <measurement group_id="B2" value="66"/>
                    <measurement group_id="B3" value="69"/>
                    <measurement group_id="B4" value="212"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="19"/>
                    <measurement group_id="B4" value="42"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="82"/>
                    <measurement group_id="B2" value="88"/>
                    <measurement group_id="B3" value="80"/>
                    <measurement group_id="B4" value="250"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="107"/>
                    <measurement group_id="B2" value="104"/>
                    <measurement group_id="B3" value="105"/>
                    <measurement group_id="B4" value="316"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title># Patients with Pre-existing Donor Specific Antibody (DSA)</title>
          <description>Patients who have the presence of a donor specific antibody (DSA) at the time of their transplant (baseline)</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>calculated panel reactive antibody (cPRA) %</title>
          <units>percentage</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="4.9" spread="12.7"/>
                    <measurement group_id="B2" value="6.4" spread="16.4"/>
                    <measurement group_id="B3" value="5.9" spread="15.7"/>
                    <measurement group_id="B4" value="5.8" spread="14.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Repeat Transplant</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Living related donor</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                    <measurement group_id="B2" value="25"/>
                    <measurement group_id="B3" value="33"/>
                    <measurement group_id="B4" value="83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Living unrelated donor</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="55"/>
                    <measurement group_id="B2" value="53"/>
                    <measurement group_id="B3" value="47"/>
                    <measurement group_id="B4" value="155"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Deceased donor</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27"/>
                    <measurement group_id="B2" value="26"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-emptive transplant</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37"/>
                    <measurement group_id="B2" value="27"/>
                    <measurement group_id="B3" value="40"/>
                    <measurement group_id="B4" value="104"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cytomegalovirus (CMV) High Risk status (D+/R-)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="25"/>
                    <measurement group_id="B4" value="64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pre-existing diabetes mellitus</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                    <measurement group_id="B2" value="33"/>
                    <measurement group_id="B3" value="33"/>
                    <measurement group_id="B4" value="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title># Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR &lt; 45ml/Min</title>
        <description>Number of Patients that experienced patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) &lt; 45 mL/min</description>
        <time_frame>12 months</time_frame>
        <population>Intent to treat analysis</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title># Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR &lt; 45ml/Min</title>
          <description>Number of Patients that experienced patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) &lt; 45 mL/min</description>
          <population>Intent to treat analysis</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="15"/>
                    <measurement group_id="O3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title># Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss)</title>
        <description>Number of patient who experienced Graft loss, not including (censored) patients who lost graft due to death</description>
        <time_frame>24 months</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title># Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss)</title>
          <description>Number of patient who experienced Graft loss, not including (censored) patients who lost graft due to death</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title># Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR &lt; 45ml/Min at 24 Months</title>
        <description>Composite Endpoint of number of patients who experienced either patient death, allograft loss, or had an eGFR &lt; 45 ml/min/1.73m2</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title># Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR &lt; 45ml/Min at 24 Months</title>
          <description>Composite Endpoint of number of patients who experienced either patient death, allograft loss, or had an eGFR &lt; 45 ml/min/1.73m2</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="13"/>
                    <measurement group_id="O3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>eGFR (MRDRD) &lt; 45 ml/Min/1.73m2</title>
        <description>Patients with reduced Renal function measured by estimated GFR MDRD &lt; 45 ml/min at 24 months</description>
        <time_frame>24 months</time_frame>
        <population>Intent to Treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>eGFR (MRDRD) &lt; 45 ml/Min/1.73m2</title>
          <description>Patients with reduced Renal function measured by estimated GFR MDRD &lt; 45 ml/min at 24 months</description>
          <population>Intent to Treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="8"/>
                    <measurement group_id="O3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biopsy Proven Acute Rejection</title>
        <description>Incidence of all biopsy proven acute rejection whether clinically relevant or clinically silent.</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Biopsy Proven Acute Rejection</title>
          <description>Incidence of all biopsy proven acute rejection whether clinically relevant or clinically silent.</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20"/>
                    <measurement group_id="O2" value="26"/>
                    <measurement group_id="O3" value="7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biopsy Proven Acute Cellular Rejection</title>
        <description>Biopsy proven acute cellular rejection (BPACR)</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Biopsy Proven Acute Cellular Rejection</title>
          <description>Biopsy proven acute cellular rejection (BPACR)</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="22"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biopsy Proven Acute Antibody Mediated Rejection</title>
        <description>Incidence of patients experiencing a Biopsy proven acute antibody mediated rejection (BPAMR)</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Biopsy Proven Acute Antibody Mediated Rejection</title>
          <description>Incidence of patients experiencing a Biopsy proven acute antibody mediated rejection (BPAMR)</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Biopsy Proven Mixed Acute Rejection</title>
        <description>Incidence of patients experiencing a Biopsy proven acute cellular rejection with either DSA positive or C4d staining positive indicating antibody rejection</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Biopsy Proven Mixed Acute Rejection</title>
          <description>Incidence of patients experiencing a Biopsy proven acute cellular rejection with either DSA positive or C4d staining positive indicating antibody rejection</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                    <measurement group_id="O2" value="2"/>
                    <measurement group_id="O3" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title># of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant</title>
        <description>Number of patients (%) with development of denovo DSA after transplant</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title># of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant</title>
          <description>Number of patients (%) with development of denovo DSA after transplant</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="89"/>
                <count group_id="O2" value="85"/>
                <count group_id="O3" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean eGFR (MDRD) (ml/Min/1.73m2)</title>
        <description>Mean eGFR (MDRD) (ml/min/1.73m2) measured for all patients reaching 2 year endpoint</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean eGFR (MDRD) (ml/Min/1.73m2)</title>
          <description>Mean eGFR (MDRD) (ml/min/1.73m2) measured for all patients reaching 2 year endpoint</description>
          <population>Intent to treat</population>
          <units>ml/min/1.73m2</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="96"/>
                <count group_id="O2" value="92"/>
                <count group_id="O3" value="97"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="65.5" spread="18.9"/>
                    <measurement group_id="O2" value="65.3" spread="19.3"/>
                    <measurement group_id="O3" value="63.4" spread="19.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Proteinuria UPC Ratio &gt; 0.8</title>
        <description>Number of Patients with a Urine protein/creatinine (UPC) ratio &gt; 0.8</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Proteinuria UPC Ratio &gt; 0.8</title>
          <description>Number of Patients with a Urine protein/creatinine (UPC) ratio &gt; 0.8</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="84"/>
                <count group_id="O2" value="85"/>
                <count group_id="O3" value="84"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Patient Death</title>
        <description>Number of Patients who experienced death, all causes</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Patient Death</title>
          <description>Number of Patients who experienced death, all causes</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2"/>
                    <measurement group_id="O2" value="4"/>
                    <measurement group_id="O3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR)</title>
        <description>Number of patients requiring anti-lymphocyte therapy for the treatment of BPAR rejection</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR)</title>
          <description>Number of patients requiring anti-lymphocyte therapy for the treatment of BPAR rejection</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8"/>
                    <measurement group_id="O2" value="15"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>New Onset Diabetes After Transplantation (NODAT)</title>
        <description>Number of patients developing New Onset Diabetes Mellitus after Transplant by one of 5 definitions; only patients without preexisting diabetes were included</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>New Onset Diabetes After Transplantation (NODAT)</title>
          <description>Number of patients developing New Onset Diabetes Mellitus after Transplant by one of 5 definitions; only patients without preexisting diabetes were included</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="80"/>
                <count group_id="O2" value="71"/>
                <count group_id="O3" value="72"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="5"/>
                    <measurement group_id="O3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Time to First BPAR</title>
        <description>Mean Time to first episode of BPAR (days)</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Time to First BPAR</title>
          <description>Mean Time to first episode of BPAR (days)</description>
          <population>Intent to treat</population>
          <units>days</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="229" spread="147.7"/>
                    <measurement group_id="O2" value="131.6" spread="119.6"/>
                    <measurement group_id="O3" value="159.6" spread="219.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title># Patients Experiencing a First Biopsy-proven ACR With Severity Banff &gt; or = 2a Grade</title>
        <description>Number of patients with their First BPACR with a Banff grade &gt;= Banff 2a using the Banff 2007 classification system for biopsy grading. Banff grade 2a and above is considered severe cellular rejection and includes grades of Banff 2a, Banff 2b, and Banff 3.</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title># Patients Experiencing a First Biopsy-proven ACR With Severity Banff &gt; or = 2a Grade</title>
          <description>Number of patients with their First BPACR with a Banff grade &gt;= Banff 2a using the Banff 2007 classification system for biopsy grading. Banff grade 2a and above is considered severe cellular rejection and includes grades of Banff 2a, Banff 2b, and Banff 3.</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                    <measurement group_id="O2" value="12"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Delayed Graft Function</title>
        <description>Number of patients experiencing Delayed graft function (DGF) within first week after transplant. DGF is defined as need for dialysis within the first week after transplant.</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Delayed Graft Function</title>
          <description>Number of patients experiencing Delayed graft function (DGF) within first week after transplant. DGF is defined as need for dialysis within the first week after transplant.</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="1"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Leukopenia (WBC &lt; 2000/mm3)</title>
        <description>Number of patients developing leukopenia defined as WBC &lt; 2000/mm3</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Leukopenia (WBC &lt; 2000/mm3)</title>
          <description>Number of patients developing leukopenia defined as WBC &lt; 2000/mm3</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Steroid Therapy</title>
        <description>Number of patients on treatment with corticosteroids at 2 years</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Steroid Therapy</title>
          <description>Number of patients on treatment with corticosteroids at 2 years</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16"/>
                    <measurement group_id="O2" value="14"/>
                    <measurement group_id="O3" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Discontinuation of Mycophenolate</title>
        <description>Number of patients who were discontinued from mycophenolate treatment at 2 years</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Discontinuation of Mycophenolate</title>
          <description>Number of patients who were discontinued from mycophenolate treatment at 2 years</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Discontinuation of Study Treatment (Belatacept or Tacrolimus)</title>
        <description>Number of patients who had to Discontinue study treatment (belatacept or tacrolimus) at 2 years</description>
        <time_frame>24 months</time_frame>
        <population>Intent to treat</population>
        <group_list>
          <group group_id="O1">
            <title>Group A</title>
            <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
          </group>
          <group group_id="O2">
            <title>Group B</title>
            <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
          </group>
          <group group_id="O3">
            <title>Group C</title>
            <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
          </group>
        </group_list>
        <measure>
          <title>Discontinuation of Study Treatment (Belatacept or Tacrolimus)</title>
          <description>Number of patients who had to Discontinue study treatment (belatacept or tacrolimus) at 2 years</description>
          <population>Intent to treat</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="107"/>
                <count group_id="O2" value="104"/>
                <count group_id="O3" value="105"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                    <measurement group_id="O2" value="9"/>
                    <measurement group_id="O3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected in every patient over a 2 year time period.</time_frame>
      <desc>The definition used for serious adverse events were the same as the standard definition. The definition for adverse events differed only in that the adverse events that were related to immunosuppression were captured and any adverse events of special interest in the study.</desc>
      <group_list>
        <group group_id="E1">
          <title>Group A</title>
          <description>Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids&#xD;
Alemtuzumab: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.&#xD;
Belatacept: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is the day of transplant.</description>
        </group>
        <group group_id="E2">
          <title>Group B</title>
          <description>Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Belatacept: Belatacept is administered via intravenous (IV) infusion according to the FDA label</description>
        </group>
        <group group_id="E3">
          <title>Group C</title>
          <description>Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids&#xD;
rabbit antithymocyte globulin: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.&#xD;
Tacrolimus: Tacrolimus will be administered orally twice daily (BID).</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="58" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="66" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="62" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>PTLD</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Cardiovascular event</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="107"/>
                <counts group_id="E2" events="12" subjects_affected="9" subjects_at_risk="104"/>
                <counts group_id="E3" events="5" subjects_affected="3" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea/vomiting or GI requiring hospitalization</sub_title>
                <counts group_id="E1" events="6" subjects_affected="4" subjects_at_risk="107"/>
                <counts group_id="E2" events="10" subjects_affected="7" subjects_at_risk="104"/>
                <counts group_id="E3" events="16" subjects_affected="13" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Malignancy</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="7" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Infection Requiring Hospitalization</sub_title>
                <description>all infections which required for participant to be hospitalized.</description>
                <counts group_id="E1" subjects_affected="24" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="24" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="23" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Mental status changes or neurological AE's</sub_title>
                <counts group_id="E1" events="8" subjects_affected="5" subjects_at_risk="107"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="104"/>
                <counts group_id="E3" events="9" subjects_affected="5" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal dysfunction resulting in hospitalization</sub_title>
                <counts group_id="E1" events="53" subjects_affected="30" subjects_at_risk="107"/>
                <counts group_id="E2" events="50" subjects_affected="32" subjects_at_risk="104"/>
                <counts group_id="E3" events="40" subjects_affected="28" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="91" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="90" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="92" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hematologic events</sub_title>
                <counts group_id="E1" subjects_affected="59" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="55" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="60" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Leukopenia WBC &lt; 2000/mm3</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="15" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Anemia (Hg &lt; 7gm/dL)</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="6" subjects_at_risk="105"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia (PLT &lt; 50,000/mm3)</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal events</sub_title>
                <counts group_id="E1" subjects_affected="32" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="34" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="50" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Electrolyte/metabolic events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="32" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal/Bone events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="5" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Neurologic events</sub_title>
                <counts group_id="E1" subjects_affected="14" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="14" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="33" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Nephrotoxicity events</sub_title>
                <counts group_id="E1" subjects_affected="22" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="28" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="37" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Wound healing</sub_title>
                <counts group_id="E1" subjects_affected="7" subjects_at_risk="107"/>
                <counts group_id="E2" subjects_affected="10" subjects_at_risk="104"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="105"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Rita R. Alloway, Pharm.D., Director of Clinical Trials</name_or_title>
      <organization>University of Cincinnati</organization>
      <phone>513-558-1568</phone>
      <email>rita.alloway@uc.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01729494
org study id: BEST
nct id: NCT01729494
lead sponsor: 
has dmc: Yes
The study purpose is to determine the safety and efficacy of a belatacept-based
      immunosuppressive regimen (calcineurin inhibitor free) with alemtuzumab or rabbit
      antithymocyte globulin (rATG) induction and early glucocorticoid withdrawal (CSWD) and a
      belatacept-based immunosuppressive regimen with tacrolimus-based regimen with rabbit
      antithymocyte globulin induction and early glucocorticoid withdrawal in renal transplant
      recipients.

      The hypothesis is that a belatacept-based immunosuppressive regimen with alemtuzumab
      induction, mycophenolate mofetil (MMF)/mycophenolic acid (MPA), and early glucocorticoid
      withdrawal (Group A) in renal transplant recipients or Belatacept-based immunosuppressive
      regimen with rabbit antithymocyte globulin induction, MMF/MPA and early glucocorticoid
      withdrawal (Group B) will lead to less risk of graft loss, patient death, or reduced renal
      function at 12 months as compared to a tacrolimus-based immunosuppressive regimen with rabbit
      antithymocyte globulin, MMF/MPA, and early glucocorticoid withdrawal in renal transplant
      recipients (Group C).
Renal transplant is the most effective treatment for end-stage renal disease. It provides
      improved survival and quality of life. Maintenance of a functioning renal transplant mandates
      lifelong immunosuppressive therapy to prevent immune destruction of the graft. Current
      immunosuppressive regimens yield 1-year survival rates of 89% for cadaveric and 94% for
      living-donor grafts. Over time, however, there is progressive loss of both subjects and
      grafts. Five-year graft survival for cadaveric and living related donor renal transplants is
      67% and 80%, respectively.

      The most common causes of long-term subject and graft loss in kidney transplant recipients
      are cardiovascular disease and chronic allograft nephropathy (CAN), respectively.
      Paradoxically, the principal immunosuppressive therapies for renal transplant, the
      calcineurin inhibitors (CNIs), cyclosporine (CsA) and tacrolimus, directly contribute to
      long-term allograft loss and subject death, since they are inherently nephrotoxic and can
      cause or exacerbate cardiovascular risks including hypertension, hypercholesterolemia, and
      diabetes mellitus.

      There is, therefore, a substantial unmet medical need for new therapies in renal transplant
      that can provide short-term subject and graft survival comparable to the CNIs without their
      long-term nephrotoxic, cardiovascular, and metabolic effects. Because belatacept can be
      administered at the time of engraftment rather than in a delayed fashion, as is frequently
      necessary with CNIs - especially in those allografts with initial impaired renal function--
      it affords immunosuppression in a timely manner. Unlike CNIs, the targeted mechanism of
      action of belatacept should provide immunosuppression without nephrotoxicity or adverse
      effects on the cardiovascular/metabolic profile.

      Glucocorticoids have been a cornerstone of immunosuppressive therapy for six decades.
      Although glucocorticoids provide potent suppression of allo-immune responses in humans, their
      adverse effects including infection, diabetes, weight gain, hypertension, hyperlipidemia,
      bone disease, dermal thinning, collagen loss in multiple tissues, and cataracts, combined
      with a lack of available therapeutic monitoring all argue against their continued use in
      transplantation.

      Belatacept represents a potential new treatment option for renal transplant recipients, which
      addresses the current unmet need for an immunosuppressive treatment that provides short-term
      outcomes comparable to calcineurin inhibitors (CNIs) with the potential to avoid their renal,
      cardiovascular, and metabolic toxicities. However, the initial Phase 3 studies exhibited in
      higher rate of acute rejection and malignancy. The malignancies were associated with
      recipients who were EBV negative at the time of transplant. All EBV negative patients are
      precluded from treatment with Belatacept. Due to the limitations of Phase 3 trial designs and
      the required use of basilixumab induction, it is intuitive that the addition of a potent t
      cell depleting induction agent may decrease the overall acute rejection rate in patients
      treated with belatacept.

      The current study tests these assumptions with the following immunosuppressive regimens.
      Group A and B consist of potent T-cell depleting induction agents combined with belatacept.
      Group C represents the most common immunosuppressive regimen currently utilized in the United
      States. Each of these regimens include early withdrawal of glucocorticoids along with
      maintenance mycophenolate mofetil.

      Based upon the totality of available evidence, the current study offers a favorable
      benefit/risk profile to study subjects, and the potential to continue to provide important
      data for the development of new immunosuppressive regimens that address important unmet
      needs.

      The proposed Phase 4 study is designed to determine whether belatacept, in combination with
      other immunosuppressive agents (rabbit antithymocyte globulin or alemtuzumab, mycophenolate
      mofetil/EC mycophenolate sodium), may provide acceptable efficacy and safety in de novo
      kidney transplant recipients, in a regimen that provides simultaneous CNI freedom and early
      CSWD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: # Patients With Composite Endpoint of Experiencing Either Death, Graft Loss, or eGFR < 45ml/Min
time frame: 12 months
description: Number of Patients that experienced patient Death or Graft Loss or had an estimated GFR (eGFR) (MDRD) < 45 mL/min
measure: # Patients Experiencing a Graft Loss But Not Including Patients Who Died With Functioning Graft (Death-censored Graft Loss)
time frame: 24 months
description: Number of patient who experienced Graft loss, not including (censored) patients who lost graft due to death
measure: # Patients With Composite Endpoint of Either Experiencing Death, Graft Loss, or eGFR < 45ml/Min at 24 Months
time frame: 24 months
description: Composite Endpoint of number of patients who experienced either patient death, allograft loss, or had an eGFR < 45 ml/min/1.73m2
measure: eGFR (MRDRD) < 45 ml/Min/1.73m2
time frame: 24 months
description: Patients with reduced Renal function measured by estimated GFR MDRD < 45 ml/min at 24 months
measure: Biopsy Proven Acute Rejection
time frame: 24 months
description: Incidence of all biopsy proven acute rejection whether clinically relevant or clinically silent.
measure: Biopsy Proven Acute Cellular Rejection
time frame: 24 months
description: Biopsy proven acute cellular rejection (BPACR)
measure: Biopsy Proven Acute Antibody Mediated Rejection
time frame: 24 months
description: Incidence of patients experiencing a Biopsy proven acute antibody mediated rejection (BPAMR)
measure: Biopsy Proven Mixed Acute Rejection
time frame: 24 months
description: Incidence of patients experiencing a Biopsy proven acute cellular rejection with either DSA positive or C4d staining positive indicating antibody rejection
measure: # of Patients Developing Denovo Donor Specific Antibody (DSA) Post-transplant
time frame: 24 months
description: Number of patients (%) with development of denovo DSA after transplant
measure: Mean eGFR (MDRD) (ml/Min/1.73m2)
time frame: 24 months
description: Mean eGFR (MDRD) (ml/min/1.73m2) measured for all patients reaching 2 year endpoint
measure: Proteinuria UPC Ratio > 0.8
time frame: 24 months
description: Number of Patients with a Urine protein/creatinine (UPC) ratio > 0.8
measure: Patient Death
time frame: 24 months
description: Number of Patients who experienced death, all causes
measure: Requirement of T-cell Depleting Therapy for Biopsy Proven Acute Rejection (BPAR)
time frame: 24 months
description: Number of patients requiring anti-lymphocyte therapy for the treatment of BPAR rejection
measure: New Onset Diabetes After Transplantation (NODAT)
time frame: 24 months
description: Number of patients developing New Onset Diabetes Mellitus after Transplant by one of 5 definitions; only patients without preexisting diabetes were included
measure: Time to First BPAR
time frame: 24 months
description: Mean Time to first episode of BPAR (days)
measure: # Patients Experiencing a First Biopsy-proven ACR With Severity Banff > or = 2a Grade
time frame: 24 months
description: Number of patients with their First BPACR with a Banff grade >= Banff 2a using the Banff 2007 classification system for biopsy grading. Banff grade 2a and above is considered severe cellular rejection and includes grades of Banff 2a, Banff 2b, and Banff 3.
measure: Delayed Graft Function
time frame: 24 months
description: Number of patients experiencing Delayed graft function (DGF) within first week after transplant. DGF is defined as need for dialysis within the first week after transplant.
measure: Leukopenia (WBC < 2000/mm3)
time frame: 24 months
description: Number of patients developing leukopenia defined as WBC < 2000/mm3
measure: Steroid Therapy
time frame: 24 months
description: Number of patients on treatment with corticosteroids at 2 years
measure: Discontinuation of Mycophenolate
time frame: 24 months
description: Number of patients who were discontinued from mycophenolate treatment at 2 years
measure: Discontinuation of Study Treatment (Belatacept or Tacrolimus)
time frame: 24 months
description: Number of patients who had to Discontinue study treatment (belatacept or tacrolimus) at 2 years
arm group label: Group A
arm group type: Experimental
description: Alemtuzumab + belatacept + mycophenolate mofetil /Enteric coated mycophenolate sodium + early cessation of steroids
arm group label: Group B
arm group type: Experimental
description: Rabbit antithymocyte globulin + belatacept + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids
arm group label: Group C
arm group type: Active Comparator
description: Rabbit antithymocyte globulin + tacrolimus + mycophenolate mofetil /Enteric coated (EC) mycophenolate sodium + early cessation of steroids
intervention type: Drug
intervention name: Alemtuzumab
description: Alemtuzumab will be dosed on day of transplant (Study Day 1) at dose of 30 mg given intravenously (IV) over a period of 2 hours after induction of anesthesia. Methylprednisolone IV will be administered 30-60 minutes prior to the administration of alemtuzumab.
arm group label: Group A
other name: Campath
intervention type: Drug
intervention name: rabbit antithymocyte globulin
description: Rabbit antithymocyte globulin will be dosed post-operatively at a total cumulative dose of 4.0-6.0mg/kg given by days 5-10 post-transplant. It will be administered by local standards of care with the following recommendations. The initial intravenous intra-operative dose will be administered approximately one hour after the methylprednisolone dose. The first dose will be administered so that approximately 25% of the dose is infused prior to revascularization of the graft. Subsequent doses will be administered over a minimum of 4 hours. Premedication with acetaminophen 650mg p.o. and diphenhydramine 25mg p.o. prior to rabbit antithymocyte globulin dose will be given to reduce the incidence of infusion reactions.
arm group label: Group B
arm group label: Group C
other name: Thymoglobulin
intervention type: Drug
intervention name: Belatacept
description: Belatacept will be administered via intravenous (IV) infusion according to the FDA approved dosage recommendations. Subjects randomized to belatacept arms will receive the first dose of IV belatacept (10 mg/kg) within 12-24 hours post reperfusion. The second dose will be given between post-transplant days 4 -6 (Study Days 5-7), and then study days 14, 28, 56, and 84 (12 weeks) and then subjects will receive belatacept at the maintenance dose of 5 mg/kg every 4 weeks until completion of the trial at 24 months (104 weeks). Study Day 1 is defined as the day of transplant.
arm group label: Group A
arm group label: Group B
other name: Nulojix
intervention type: Drug
intervention name: Tacrolimus
description: Tacrolimus will be administered orally twice daily (BID). The recommended total initial dose of tacrolimus is 0.1 mg/kg/day in two divided doses orally. Tacrolimus should be started post-transplant within 48 hours or when serum creatinine drops lower than 4mg/dL, whichever comes first. The initial targeted trough level of tacrolimus will be 8 - 12 ng/mL for Days 1 through 30, with dose reduction to achieve a 12-hour trough target of 5 - 10 ng/mL thereafter.
arm group label: Group C
other name: Prograf, various
intervention type: Drug
intervention name: Mycophenolate mofetil
description: The first dose of mycophenolate mofetil/EC mycophenolate sodium will be administered pre-operatively. Patients receiving mycophenolate mofetil will be dosed 1000 mg twice daily (2000mg/day). Patients receiving EC mycophenolate sodium will be dosed 720 mg twice daily (1440 mg/day). Dose may be increased for African American transplant recipients to mycophenolate mofetil 1500 mg twice daily (3000mg/day) or EC mycophenolate sodium 1080 mg twice daily (2160 mg/day).
arm group label: Group A
arm group label: Group B
arm group label: Group C
other name: Cellcept, various, Myfortic
intervention type: Drug
intervention name: early cessation of steroids
description: Glucocorticoid therapy will be administered as described. Methylprednisolone will be administered on Days 1 through 3. Additional tapering doses of glucocorticoids will continue to be given until Day 5 as below:
Day 1 (day of transplant): 500mg IV prior to alemtuzumab (Group A) or rabbit antithymocyte globulin (Groups B and C) Day 2: 250mg IV Day 3: 125mg IV Day 4: 80mg p.o. Day 5: 60mg p.o. No further steroids
arm group label: Group A
arm group label: Group B
arm group label: Group C
other name: prednisone, various
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: E. Steve Woodle, MD
role: Principal Investigator
affiliation: University of Cincinnati
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country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Cincinnati
investigator full name: E. Steve Woodle
investigator title: MD, FACS
mesh term: Mycophenolic Acid
mesh term: Prednisone
mesh term: Alemtuzumab
mesh term: Abatacept
mesh term: Tacrolimus
mesh term: Thymoglobulin
mesh term: Antilymphocyte Serum
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