<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/NCT03037164</url>
  </required_header>
  <id_info>
    <org_study_id>CLI 00126</org_study_id>
    <nct_id>NCT03037164</nct_id>
  </id_info>
  <brief_title>INTERCEPT Blood System for RBCs Study in Regions at Potential Risk for Zika Virus Transfusion-Transmitted Infections</brief_title>
  <acronym>RedeS</acronym>
  <official_title>Randomized, Double-Blind, Controlled, Parallel Group Study With the INTERCEPT Blood System for RBCs in Regions at Potential Risk for Zika Virus Transfusion-Transmitted Infections and Treatment Use Open-Label Extension Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Cerus Corporation</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Cerus Corporation</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Stage A: To evaluate the safety and efficacy of red blood cells (RBCs) prepared with the&#xD;
      INTERCEPT Blood System for Red Blood Cells Pathogen Reduction Treatment (PRT) in comparison&#xD;
      to conventional RBCs in patients who require RBC transfusion support.&#xD;
&#xD;
      Stage B: To provide early access to the INTERCEPT pathogen reduction system for RBC in&#xD;
      regions where a substantial proportion of the population has been infected or is at risk of a&#xD;
      transfusion-transmissible infection.&#xD;
&#xD;
      The objectives and design of Stage B will be reassessed on the completion of Stage A, in&#xD;
      consultation with the FDA.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Stage A&#xD;
&#xD;
      Patients will be approached, consented, screened for eligibility and randomized to receive&#xD;
      either Test or Control RBCs in one of the three arms at the beginning of the study:&#xD;
&#xD;
        -  Bleeding or non-bleeding patients at baseline may be enrolled into the 28-day&#xD;
           transfusion period.&#xD;
&#xD;
        -  Non-bleeding patients at baseline with chronic anemia requiring repeated simple&#xD;
           transfusion may be enrolled into the 28-day +6-month extension period.&#xD;
&#xD;
        -  SCD on a regular repeated RCE program at baseline may be enrolled into 28-day +6-month&#xD;
           extension period to receive 3 consecutive RCE procedures.&#xD;
&#xD;
      Eligible patients will be randomized and transfused with study RBCs (Test or Control with 1:1&#xD;
      ratio) according to local practices for up to 28 days of transfusion support. Following the&#xD;
      28-day acute transfusion support period, patients will be transfused with conventional RBC&#xD;
      components as indicated by their treating physician unless they were enrolled at baseline in&#xD;
      the optional 6-month extension period.&#xD;
&#xD;
      Non-bleeding patients at baseline requiring repeated RBC transfusion for congenital or&#xD;
      acquired chronic anemia (e.g., sickle anemia, thalassemia, other hemoglobinopathies,&#xD;
      myelodysplastic syndrome, aplastic anemia, chemotherapy or stem cell transplant etc.) will be&#xD;
      eligible to participate in an extension option for up to 6 months to evaluate patients&#xD;
      requiring repeated transfusion for chronic anemia.&#xD;
&#xD;
      In addition, SCD patients on a regular RCE program at 2 or more clinical sites may be&#xD;
      enrolled at baseline into the 6-month extension period to receive up to a total of 3&#xD;
      consecutive RCE procedures.&#xD;
&#xD;
      Screening/Recruitment&#xD;
&#xD;
      All potentially eligible patients at participating institutions will be approached for study&#xD;
      consent. Subjects &lt;18 years of age will require subject assent and parental consent. For&#xD;
      subjects eligible for enrollment into the 6-month extension period option, consent/assent for&#xD;
      the extension period should be obtained at initial enrollment.&#xD;
&#xD;
      Patients who consent to the study will be assigned a study ID number and undergo screening.&#xD;
      Screening data collection and procedures will include:&#xD;
&#xD;
      Demographics (age, sex), vital signs, height, weight, indication for anticipated transfusion,&#xD;
      type of scheduled surgery (if applicable), medical and surgical history, transfusion history,&#xD;
      physical examination, comorbid conditions, concomitant medications, hematology panel&#xD;
      (including complete blood count), blood type and Rh, Indirect Antiglobulin Test (IAT), blood&#xD;
      chemistry, coagulation panel, Direct Antiglobulin Test (DAT), immune reactivity to IBS RBCs&#xD;
      (if available), pregnancy test (when applicable). Once all screening assessments are&#xD;
      completed and eligibility is confirmed, the subject may be randomized.&#xD;
&#xD;
      For SCD patients on a regular RCE program, if available in the medical record, the pre- and&#xD;
      post- RCE total Hemoglobin, HbA, HbS and HgF concentrations should be recorded for up to 6&#xD;
      months prior to the first study transfusion.&#xD;
&#xD;
      If results from the following assessments are available in the medical record within 30 days&#xD;
      prior to randomization, those data may serve as the screening data and the assessments do not&#xD;
      need to be repeated unless the subject has an RBC transfusion in the 30-day period:&#xD;
&#xD;
        -  hematology panel (complete blood count), blood chemistry and coagulation panel&#xD;
&#xD;
        -  blood type and Rh&#xD;
&#xD;
        -  IAT, DAT, and immune reactivity to IBS RBCs&#xD;
&#xD;
        -  physical examination&#xD;
&#xD;
      If an RBC transfusion occurs after the study specific blood draws and assessments to&#xD;
      determine eligibility are taken but prior to randomization, the subject may be randomized and&#xD;
      the tests listed above should repeated prior to the first study transfusion.&#xD;
&#xD;
      A pregnancy test (when applicable) must be performed within 7 days of randomization.&#xD;
&#xD;
      Randomization and Blinding&#xD;
&#xD;
      For Stage A, potentially eligible patients will be consented and begin screening in the study&#xD;
      in order to be assessed for eligibility for one of the three study arms and to be considered&#xD;
      for randomization to receive Test or Control RBCs. An Interactive Web Response System (IWRS)&#xD;
      will be used for electronic randomization of eligible patients.&#xD;
&#xD;
      Randomization will be at a 1:1 ratio of Test: Control to receive either Test or Control RBCs&#xD;
      and stratified by site, baseline bleeding status [indication for RBC transfusion due to&#xD;
      active bleeding (WHO Grade 3 or 4, APPENDIX 5) or for anemia without active bleeding], and&#xD;
      participation of the optional extension period (yes/no). Anticipated surgical bleeding and&#xD;
      planned blood loss/replacement through RCE at baseline should be included as active bleeding&#xD;
      (Grade ≥3) by definition. Randomized patients who do not receive any study RBC transfusions&#xD;
      through 28 days after randomization will be withdrawn from the study and replaced. Additional&#xD;
      data will not be collected for these patients. These subjects may be reassessed for&#xD;
      eligibility and re-enrollment after withdrawal.&#xD;
&#xD;
      At the end of screening, the patient's eligibility status will be entered into the electronic&#xD;
      data capture system (EDC). If eligible, the patient will be randomized. Only appropriate&#xD;
      blood bank staff will be able to access the treatment arm assignment. Study RBC unit labels&#xD;
      will be indistinguishable for Test and Control products. Medical staff, and others caring for&#xD;
      participating patients, as well as the sponsor (and delegates) will be blinded to treatment&#xD;
      assignment. Unblinded delegates will monitor the production of the RBC components at&#xD;
      designated blood centers.&#xD;
&#xD;
      Treatment&#xD;
&#xD;
      Randomized patients will be transfused with Test or Control RBC components for up to 28 days&#xD;
      in the initial acute transfusion period and for an additional 6-months if the subject is&#xD;
      entered into the optional extension period. Subjects participating in Stage A's optional&#xD;
      extended study will continue to receive the same study article (Test or Control RBC) as in&#xD;
      their initial 28-day study period. Following participation in the optional 6-month extended&#xD;
      transfusion support period, patients will be transfused with conventional RBC components as&#xD;
      indicated by their treating physician.&#xD;
&#xD;
      An RBC transfusion episode is defined to include consecutive RBC units transfused until the&#xD;
      next post-transfusion Hb determination with ≤12 hours between transfusions (from the end of a&#xD;
      prior component transfused to the start of a subsequent component transfused).&#xD;
&#xD;
      A confirmed negative immune reaction to IBS RBC is required prior to the first study&#xD;
      transfusion and at every time point a Type/Rh and Screen (IAT) is performed for a patient&#xD;
      within the 28-day acute transfusion period or during the extension period. Compatibility for&#xD;
      RBC antigens will be confirmed using site's SOPs prior to transfusion of study RBCs. In case&#xD;
      of confirmed physiologically active antibodies to IBS RBC or any presumed or documented&#xD;
      antibodies to IBS RBC that preclude further transfusion with study RBCs, patients will be&#xD;
      withdrawn from the study treatment and supported with conventional RBC components and&#xD;
      followed for safety. Patients with antibodies to IBS RBC will be investigated for evidence of&#xD;
      hemolysis and continue with all planned visits and safety monitoring.&#xD;
&#xD;
      SCD patients on a regular RCE program enrolled into the 6-month extension period will receive&#xD;
      3 consecutive RCE procedures with study RBC with an interval of 3-8 weeks between RCE&#xD;
      procedures, as determined by their physician.&#xD;
&#xD;
      Study Assessments: Monitoring and Follow-up&#xD;
&#xD;
      Acute Transfusion Support Period (First study transfusion through Day 28 or death) and the&#xD;
      optional extension period (if applicable).&#xD;
&#xD;
      The acute transfusion support period will comprise 28 days from the day of the first study&#xD;
      transfusion (Day 1) through Day 28, or death of a patient, plus an additional optional&#xD;
      6-month transfusion period for those patients entered into the extension period. During these&#xD;
      periods, patients will receive as many study RBCs as deemed appropriate by the treating&#xD;
      physician. All AEs, SAEs, TRs and unanticipated adverse device effects will be collected&#xD;
      starting from the initiation of the first study transfusion through 28 days after the last&#xD;
      study transfusion. The Investigators will assess each AE/SAE/TR and unanticipated adverse&#xD;
      device effects for relation to the transfused study RBCs. Transfusion reactions will be&#xD;
      classified by the definitions in the CDC NHSN Hemovigilance Module Surveillance Protocol&#xD;
      (APPENDIX 1, 2 &amp; 3) and will be captured in the eCRF and, if in routine use, in the CDC NHSN&#xD;
      Biovigilance Component/Hemovigilance Module (www.cdc.gov/nhsn).&#xD;
&#xD;
      Most proximate vital signs in the medical record will be collected prior to and following&#xD;
      each study transfusion. The subject's hemoglobin value will be collected from the medical&#xD;
      record, or if not available, a study sample will be submitted for testing, prior to and&#xD;
      following each study transfusion episode within 15 minutes to 24 hours after the end of the&#xD;
      transfusion episode and before the next RBC transfusion.&#xD;
&#xD;
      Relevant concomitant medications taken during the study and blood products transfused will be&#xD;
      recorded with indication, total daily dose, and dates of drug administration.&#xD;
&#xD;
      During the acute transfusion support period, patients will undergo the following assessments&#xD;
      prior to each transfusion episode: vital signs, AEs, TRs, SAEs and unanticipated adverse&#xD;
      device effects, comorbid conditions, blood samples for safety labs (complete blood count,&#xD;
      blood chemistry panel), IAT and immune reactivity to IBS RBCs. Samples may be used for&#xD;
      additional in vitro research tests as required to confirm transfusion-transmitted pathogen&#xD;
      mediated infections.&#xD;
&#xD;
      An immune reactivity to IBS RBCs test will be performed and resulted each time an IAT is&#xD;
      performed within the 28-day acute and 6-month extension transfusion support period.&#xD;
&#xD;
      For SCD patients undergoing regular RCE, the following parameters should be assessed before&#xD;
      and 15 mins to 4 hours after each RCE procedure:&#xD;
&#xD;
        -  Complete blood count including Hb and reticulocytes; and proportion (%) of HbS, HbA, and&#xD;
           HbF.&#xD;
&#xD;
        -  Coagulation panel (INR, PT, aPTT).&#xD;
&#xD;
        -  Plasma frozen sample for determination of S-300 and GSH concentrations.&#xD;
&#xD;
      Day 14 ±7 days after each RCE procedure for SCD patients undergoing regular RCE:&#xD;
&#xD;
      • Complete blood count including Hb and reticulocytes; and proportion (%) of HbS, HbA, and&#xD;
      HbF.&#xD;
&#xD;
      Follow-Up Period (28 and 75 days after last study transfusion) for all transfused patients:&#xD;
&#xD;
      For the purposes of the Day 28 (± 7 days) and Day 75 (± 15 days) follow-up visits, Day 1 of&#xD;
      the follow-up period is the day after the last study transfusion, either in the initial&#xD;
      28-day acute transfusion period or, if the subject is entered, in the optional extension&#xD;
      period.&#xD;
&#xD;
      Day 28 (± 7 days) After the Last Study Transfusion (or before first post-study RCE with&#xD;
      conventional RBCs in patients on a regular RCE program):&#xD;
&#xD;
      Vital signs will be collected, and blood samples will be collected for:&#xD;
&#xD;
        1. Routine safety labs (complete blood count, blood chemistry panel, hematology panel, and&#xD;
           coagulation panel)&#xD;
&#xD;
        2. DAT and IAT&#xD;
&#xD;
        3. Immune reactivity test for IBS RBC&#xD;
&#xD;
        4. For SCD patients undergoing regular RCE:&#xD;
&#xD;
             -  Complete blood count including Hb and reticulocytes; and proportion (%) of HbS,&#xD;
                HbA, and HbF.&#xD;
&#xD;
             -  Plasma frozen sample for determination of S-300 and GSH concentrations.&#xD;
&#xD;
      All AEs, SAEs, TRs and unanticipated adverse device effects will be reviewed and recorded for&#xD;
      the period from the first study transfusion through 28 days after the last study transfusion.&#xD;
&#xD;
      End of Study Visit (Day 75 ±15 days) for all transfused patients:&#xD;
&#xD;
      Day 75 (± 15 days) after the last study transfusion either in the initial 28-day acute&#xD;
      transfusion period or after the extension period, a blood sample will be collected for a DAT&#xD;
      and immune reactivity test for IBS RBC.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">May 11, 2017</start_date>
  <completion_date type="Anticipated">January 30, 2026</completion_date>
  <primary_completion_date type="Anticipated">October 31, 2025</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adjusted hemoglobin increment</measure>
    <time_frame>15 minutes - 24 hours post transfusion</time_frame>
    <description>The difference between the pre-transfusion and post transfusion episode hemoglobin values divided by the total hemoglobin content transfused, averaged over one or more transfusion episodes in patients without active bleeding at baseline (active bleeding is defined as WHO Grade 3 or 4 bleeding)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>28 days</time_frame>
    <description>Proportion of patients with any treatment-emergent adverse events (AEs) possibly, probably, or definitely related to study RBC transfusion through 28 days after the last study transfusion.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Treatment emergent antibodies</measure>
    <time_frame>75 days</time_frame>
    <description>The proportion of patients with treatment emergent antibodies with confirmed specificity to IBS RBCs</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Adjusted hemoglobin consumption</measure>
    <time_frame>211 Days</time_frame>
    <description>Defined as total hemoglobin mass transfused in grams divided by body weight in kg at baseline and duration of the study transfusion period in days (g/kg/day), in patients without active bleeding at baseline.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA clearance</measure>
    <time_frame>211 days</time_frame>
    <description>HbA clearance in patients with SCD undergoing regular repeated RCE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>28 Days after last study transfusion</time_frame>
    <description>Treatment-emergent AEs</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Transfusion reactions related to study RBCs (test or control)</measure>
    <time_frame>28 Days after last study transfusion</time_frame>
    <description>Defined by the CDC National Healthcare Safety Network [NHSN] Hemovigilance Module protocol</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>RBC allo-antigens</measure>
    <time_frame>28 days</time_frame>
    <description>Treatment-emergent immunization to RBC allo-antigens</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mortality</measure>
    <time_frame>28 Days after last study transfusion</time_frame>
    <description>All-cause mortality</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events of Special Interest (AESI)</measure>
    <time_frame>28 Days after last study RCE</time_frame>
    <description>Proportion of subjects with adverse events of special interest (AESI) through 28 days after the last study transfusion.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>S-300 and GSH plasma levels</measure>
    <time_frame>15 minutes to 4 hrs after RCE</time_frame>
    <description>S-300 and Glutathione (GSH) plasma levels</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">800</enrollment>
  <condition>Anemia</condition>
  <arm_group>
    <arm_group_label>INTERCEPT (Test)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Red blood cell components treated with the INTERCEPT Blood System for Red Blood Cells ordered and administered to study patients by their treating physicians according to the local standards of care</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Conventional (Control)</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Conventional RBC components ordered and administered to study patients by their treating physicians according to the local standards of care</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>INTERCEPT Blood System for Red Blood Cells</intervention_name>
    <description>The pathogen reduction process begins with a unit of RBCs derived from whole blood that is separated according to local regulations and standard operating procedures at the Blood Centers. RBCs are suspended in AS-5 or SAG-M for non-US sites. Leukocyte-reduction of whole blood or RBCs will be performed per manufacturer's instructions. The INTERCEPT Blood System process is performed on a single unit of leukocyte-depleted RBC in AS-5.</description>
    <arm_group_label>INTERCEPT (Test)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Conventional (Control)</intervention_name>
    <description>Conventional RBC components ordered and administered to study patients by their treating physicians according to the local standards of care</description>
    <arm_group_label>Conventional (Control)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Stage A: Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 4 years.&#xD;
&#xD;
          -  Patients who require or are expected to require a transfusion of RBC component(s),&#xD;
             including red cell exchange transfusion&#xD;
&#xD;
          -  Signed and dated informed consent form.&#xD;
&#xD;
          -  Female patients of child-bearing potential must:&#xD;
&#xD;
               -  Have negative serum or urine pregnancy tests prior to study treatment to rule out&#xD;
                  pregnancy, and&#xD;
&#xD;
               -  Agree to use to use at least one method of birth control that results in a low&#xD;
                  failure rate (i.e., less than 1% per year) when used consistently and correctly&#xD;
                  such as implants, injectables, combined oral contraceptives, some intrauterine&#xD;
                  devices (IUDs), sexual abstinence or vasectomized partner for the duration of&#xD;
                  study participation and an additional 28 days.&#xD;
&#xD;
        For 28-day +6-month extension study in chronically transfused patients:&#xD;
&#xD;
        • A diagnosis of a bone marrow failure syndrome requiring repeated RBC transfusion for&#xD;
        congenital or acquired chronic anemia (e.g., sickle cell anemia, thalassemia, other&#xD;
        hemoglobinopathies, myelodysplastic syndrome, aplastic anemia, chemotherapy or stem cell&#xD;
        transplant etc.)&#xD;
&#xD;
        For 28-day +6-month extension study in SCD patients requiring regular repeated RCE.&#xD;
&#xD;
          -  Diagnosis of SCD, either HbSS, HbSC or HbSB0 thalassemia, confirmed by Hb&#xD;
             electrophoresis, deoxyribonucleic acid (DNA) analysis or high-performance liquid&#xD;
             chromatography (HPLC)&#xD;
&#xD;
          -  Currently participating in an automated RCE transfusion program (for at least 3 months&#xD;
             prior to enrollment) with 3-to-8 week intervals between RCE transfusion episodes&#xD;
&#xD;
        Stage A: Exclusion Criteria&#xD;
&#xD;
          -  Confirmed positive baseline serum/plasma antibody specific to IBS RBC (S 303 treated&#xD;
             RBC) as determined by INTERCEPT S 303 antibody screening panel prior to receiving the&#xD;
             first study transfusion&#xD;
&#xD;
          -  Pregnant or breast feeding.&#xD;
&#xD;
          -  Presence of an RBC warm autoantibody with evidence of active hemolysis.&#xD;
&#xD;
          -  Positive DAT as defined below:&#xD;
&#xD;
               -  A polyspecific-DAT reaction strength &gt; 2+, or&#xD;
&#xD;
               -  A polyspecific-DAT (any strength) in conjunction with pan-reactivity with a&#xD;
                  commercial IAT antibody screening panel that precludes the identification of&#xD;
                  underlying alloantibodies or indicates the presence of autoantibody.&#xD;
&#xD;
          -  Have had an RBC transfusion within 7 days prior to randomization.&#xD;
&#xD;
          -  Have received investigational products, including investigational blood products,&#xD;
             pharmacologic agents or imaging materials, within 28 days prior to randomization.&#xD;
             Prior receipt of conventional blood products tested with an investigational NAT test&#xD;
             is not considered ground for exclusion.&#xD;
&#xD;
          -  Patients presenting with or expected to have massive hemorrhage (≥10 RBC units within&#xD;
             24 hours) or expected to require massive transfusion protocols. Planned red cell&#xD;
             exchange does not apply.&#xD;
&#xD;
          -  Patients who require neonatal transfusions and intrauterine transfusions.&#xD;
&#xD;
          -  Pre-existing antibody to RBC antigens that may make the provision of compatible study&#xD;
             RBC components difficult.&#xD;
&#xD;
          -  History of transfusion reactions requiring washed RBCs, volume reduced RBC, or RBCs&#xD;
             with additive solution removed.&#xD;
&#xD;
          -  Patients with documented IgA deficiency or a history of severe allergic reactions to&#xD;
             blood products.&#xD;
&#xD;
          -  For SCD patients to be enrolled into the repeated RCE 28-day +6-month arm of the&#xD;
             study:&#xD;
&#xD;
               -  A history of acute chest syndrome in the last 6 months, or hyperhemolysis&#xD;
                  syndrome at any time.&#xD;
&#xD;
               -  Clinical evidence of splenic hyperfunction or splenic enlargement: ≥18 cm in&#xD;
                  longitudinal diameter (diagnosed at the Investigator's discretion according to&#xD;
                  the data available, with ultrasound data being preferable).&#xD;
&#xD;
               -  Currently receiving chemotherapy for treatment of cancer. Hydroxyurea for SCD is&#xD;
                  acceptable if subject has been on stable therapy for 3 months and no changes to&#xD;
                  dosage are planned.&#xD;
&#xD;
               -  Subject is in active treatment with renal dialysis.&#xD;
&#xD;
               -  Any subject for whom a substantial change in the number of RBC components&#xD;
                  transfused is anticipated due to anticipated splenectomy, bone marrow transplant,&#xD;
                  surgery or other change in clinical status.&#xD;
&#xD;
               -  Subject with known G6PD deficiency or requiring treatment with medications that&#xD;
                  are known to adversely affect RBC viability or bone marrow function.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Chris Marston</last_name>
    <phone>1-949-275-8702</phone>
    <email>cmarston@cerus.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Tino LoSicco, Ph.D</last_name>
    <phone>901-336-1353</phone>
    <email>tlosicco@cerus.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Phoenix Children's Hospital (PCH)</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85016</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frank Nizzi, Dr.</last_name>
      <email>fnizzi@phoenixchildrens.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Yale University</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06520</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic Jacksonville</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32224</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Grady Health System</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30303</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ross Fasano, MD</last_name>
      <email>scdresearch@emory.edu</email>
    </contact>
    <contact_backup>
      <last_name>Hailly Butler, BSN</last_name>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>CHOA (Children's Healthcare of Atlanta)</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30316</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ross Fasano, Dr.</last_name>
      <email>ross.fasano@emory.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>C4TKs (Cure 4 The Kids)</name>
      <address>
        <city>Las Vegas</city>
        <state>Nevada</state>
        <zip>89135</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Joseph Lasky, Dr</last_name>
      <email>jlasky@cure4thekids.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>UT Southwestern Medical Center</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75390</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ravi Sarode, MD</last_name>
      <email>Ravi.Sarode@UTSouthwestern.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Baylor St. Luke's Medical Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77303</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Arthur Bracey, MD</last_name>
      <email>arthur.bracey@commonspirit.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Virginia Commonwealth University</name>
      <address>
        <city>Richmond</city>
        <state>Virginia</state>
        <zip>23298</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>Menonita General Hospital</name>
      <address>
        <city>Aibonito</city>
        <zip>00705</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>HIMA San Pablo Hospital</name>
      <address>
        <city>Caguas</city>
        <zip>00725</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location>
    <facility>
      <name>San Juan Bautista School of Medicine Clinical Research Unit</name>
      <address>
        <city>Caguas</city>
        <zip>00725</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2023</verification_date>
  <study_first_submitted>January 26, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>September 11, 2023</last_update_submitted>
  <last_update_submitted_qc>September 11, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>INTERCEPT</keyword>
  <keyword>Red Blood Cells</keyword>
  <keyword>RBC</keyword>
  <keyword>Pathogen Inactivation</keyword>
  <keyword>Zika</keyword>
  <keyword>Cerus</keyword>
  <keyword>Pathogen Reduction</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Transfusion Reaction</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03037164
org study id: CLI 00126
nct id: NCT03037164
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
Stage A: To evaluate the safety and efficacy of red blood cells (RBCs) prepared with the
      INTERCEPT Blood System for Red Blood Cells Pathogen Reduction Treatment (PRT) in comparison
      to conventional RBCs in patients who require RBC transfusion support.

      Stage B: To provide early access to the INTERCEPT pathogen reduction system for RBC in
      regions where a substantial proportion of the population has been infected or is at risk of a
      transfusion-transmissible infection.

      The objectives and design of Stage B will be reassessed on the completion of Stage A, in
      consultation with the FDA.
Stage A

      Patients will be approached, consented, screened for eligibility and randomized to receive
      either Test or Control RBCs in one of the three arms at the beginning of the study:

        -  Bleeding or non-bleeding patients at baseline may be enrolled into the 28-day
           transfusion period.

        -  Non-bleeding patients at baseline with chronic anemia requiring repeated simple
           transfusion may be enrolled into the 28-day +6-month extension period.

        -  SCD on a regular repeated RCE program at baseline may be enrolled into 28-day +6-month
           extension period to receive 3 consecutive RCE procedures.

      Eligible patients will be randomized and transfused with study RBCs (Test or Control with 1:1
      ratio) according to local practices for up to 28 days of transfusion support. Following the
      28-day acute transfusion support period, patients will be transfused with conventional RBC
      components as indicated by their treating physician unless they were enrolled at baseline in
      the optional 6-month extension period.

      Non-bleeding patients at baseline requiring repeated RBC transfusion for congenital or
      acquired chronic anemia (e.g., sickle anemia, thalassemia, other hemoglobinopathies,
      myelodysplastic syndrome, aplastic anemia, chemotherapy or stem cell transplant etc.) will be
      eligible to participate in an extension option for up to 6 months to evaluate patients
      requiring repeated transfusion for chronic anemia.

      In addition, SCD patients on a regular RCE program at 2 or more clinical sites may be
      enrolled at baseline into the 6-month extension period to receive up to a total of 3
      consecutive RCE procedures.

      Screening/Recruitment

      All potentially eligible patients at participating institutions will be approached for study
      consent. Subjects <18 years of age will require subject assent and parental consent. For
      subjects eligible for enrollment into the 6-month extension period option, consent/assent for
      the extension period should be obtained at initial enrollment.

      Patients who consent to the study will be assigned a study ID number and undergo screening.
      Screening data collection and procedures will include:

      Demographics (age, sex), vital signs, height, weight, indication for anticipated transfusion,
      type of scheduled surgery (if applicable), medical and surgical history, transfusion history,
      physical examination, comorbid conditions, concomitant medications, hematology panel
      (including complete blood count), blood type and Rh, Indirect Antiglobulin Test (IAT), blood
      chemistry, coagulation panel, Direct Antiglobulin Test (DAT), immune reactivity to IBS RBCs
      (if available), pregnancy test (when applicable). Once all screening assessments are
      completed and eligibility is confirmed, the subject may be randomized.

      For SCD patients on a regular RCE program, if available in the medical record, the pre- and
      post- RCE total Hemoglobin, HbA, HbS and HgF concentrations should be recorded for up to 6
      months prior to the first study transfusion.

      If results from the following assessments are available in the medical record within 30 days
      prior to randomization, those data may serve as the screening data and the assessments do not
      need to be repeated unless the subject has an RBC transfusion in the 30-day period:

        -  hematology panel (complete blood count), blood chemistry and coagulation panel

        -  blood type and Rh

        -  IAT, DAT, and immune reactivity to IBS RBCs

        -  physical examination

      If an RBC transfusion occurs after the study specific blood draws and assessments to
      determine eligibility are taken but prior to randomization, the subject may be randomized and
      the tests listed above should repeated prior to the first study transfusion.

      A pregnancy test (when applicable) must be performed within 7 days of randomization.

      Randomization and Blinding

      For Stage A, potentially eligible patients will be consented and begin screening in the study
      in order to be assessed for eligibility for one of the three study arms and to be considered
      for randomization to receive Test or Control RBCs. An Interactive Web Response System (IWRS)
      will be used for electronic randomization of eligible patients.

      Randomization will be at a 1:1 ratio of Test: Control to receive either Test or Control RBCs
      and stratified by site, baseline bleeding status [indication for RBC transfusion due to
      active bleeding (WHO Grade 3 or 4, APPENDIX 5) or for anemia without active bleeding], and
      participation of the optional extension period (yes/no). Anticipated surgical bleeding and
      planned blood loss/replacement through RCE at baseline should be included as active bleeding
      (Grade ≥3) by definition. Randomized patients who do not receive any study RBC transfusions
      through 28 days after randomization will be withdrawn from the study and replaced. Additional
      data will not be collected for these patients. These subjects may be reassessed for
      eligibility and re-enrollment after withdrawal.

      At the end of screening, the patient's eligibility status will be entered into the electronic
      data capture system (EDC). If eligible, the patient will be randomized. Only appropriate
      blood bank staff will be able to access the treatment arm assignment. Study RBC unit labels
      will be indistinguishable for Test and Control products. Medical staff, and others caring for
      participating patients, as well as the sponsor (and delegates) will be blinded to treatment
      assignment. Unblinded delegates will monitor the production of the RBC components at
      designated blood centers.

      Treatment

      Randomized patients will be transfused with Test or Control RBC components for up to 28 days
      in the initial acute transfusion period and for an additional 6-months if the subject is
      entered into the optional extension period. Subjects participating in Stage A's optional
      extended study will continue to receive the same study article (Test or Control RBC) as in
      their initial 28-day study period. Following participation in the optional 6-month extended
      transfusion support period, patients will be transfused with conventional RBC components as
      indicated by their treating physician.

      An RBC transfusion episode is defined to include consecutive RBC units transfused until the
      next post-transfusion Hb determination with ≤12 hours between transfusions (from the end of a
      prior component transfused to the start of a subsequent component transfused).

      A confirmed negative immune reaction to IBS RBC is required prior to the first study
      transfusion and at every time point a Type/Rh and Screen (IAT) is performed for a patient
      within the 28-day acute transfusion period or during the extension period. Compatibility for
      RBC antigens will be confirmed using site's SOPs prior to transfusion of study RBCs. In case
      of confirmed physiologically active antibodies to IBS RBC or any presumed or documented
      antibodies to IBS RBC that preclude further transfusion with study RBCs, patients will be
      withdrawn from the study treatment and supported with conventional RBC components and
      followed for safety. Patients with antibodies to IBS RBC will be investigated for evidence of
      hemolysis and continue with all planned visits and safety monitoring.

      SCD patients on a regular RCE program enrolled into the 6-month extension period will receive
      3 consecutive RCE procedures with study RBC with an interval of 3-8 weeks between RCE
      procedures, as determined by their physician.

      Study Assessments: Monitoring and Follow-up

      Acute Transfusion Support Period (First study transfusion through Day 28 or death) and the
      optional extension period (if applicable).

      The acute transfusion support period will comprise 28 days from the day of the first study
      transfusion (Day 1) through Day 28, or death of a patient, plus an additional optional
      6-month transfusion period for those patients entered into the extension period. During these
      periods, patients will receive as many study RBCs as deemed appropriate by the treating
      physician. All AEs, SAEs, TRs and unanticipated adverse device effects will be collected
      starting from the initiation of the first study transfusion through 28 days after the last
      study transfusion. The Investigators will assess each AE/SAE/TR and unanticipated adverse
      device effects for relation to the transfused study RBCs. Transfusion reactions will be
      classified by the definitions in the CDC NHSN Hemovigilance Module Surveillance Protocol
      (APPENDIX 1, 2 & 3) and will be captured in the eCRF and, if in routine use, in the CDC NHSN
      Biovigilance Component/Hemovigilance Module (www.cdc.gov/nhsn).

      Most proximate vital signs in the medical record will be collected prior to and following
      each study transfusion. The subject's hemoglobin value will be collected from the medical
      record, or if not available, a study sample will be submitted for testing, prior to and
      following each study transfusion episode within 15 minutes to 24 hours after the end of the
      transfusion episode and before the next RBC transfusion.

      Relevant concomitant medications taken during the study and blood products transfused will be
      recorded with indication, total daily dose, and dates of drug administration.

      During the acute transfusion support period, patients will undergo the following assessments
      prior to each transfusion episode: vital signs, AEs, TRs, SAEs and unanticipated adverse
      device effects, comorbid conditions, blood samples for safety labs (complete blood count,
      blood chemistry panel), IAT and immune reactivity to IBS RBCs. Samples may be used for
      additional in vitro research tests as required to confirm transfusion-transmitted pathogen
      mediated infections.

      An immune reactivity to IBS RBCs test will be performed and resulted each time an IAT is
      performed within the 28-day acute and 6-month extension transfusion support period.

      For SCD patients undergoing regular RCE, the following parameters should be assessed before
      and 15 mins to 4 hours after each RCE procedure:

        -  Complete blood count including Hb and reticulocytes; and proportion (%) of HbS, HbA, and
           HbF.

        -  Coagulation panel (INR, PT, aPTT).

        -  Plasma frozen sample for determination of S-300 and GSH concentrations.

      Day 14 ±7 days after each RCE procedure for SCD patients undergoing regular RCE:

      • Complete blood count including Hb and reticulocytes; and proportion (%) of HbS, HbA, and
      HbF.

      Follow-Up Period (28 and 75 days after last study transfusion) for all transfused patients:

      For the purposes of the Day 28 (± 7 days) and Day 75 (± 15 days) follow-up visits, Day 1 of
      the follow-up period is the day after the last study transfusion, either in the initial
      28-day acute transfusion period or, if the subject is entered, in the optional extension
      period.

      Day 28 (± 7 days) After the Last Study Transfusion (or before first post-study RCE with
      conventional RBCs in patients on a regular RCE program):

      Vital signs will be collected, and blood samples will be collected for:

        1. Routine safety labs (complete blood count, blood chemistry panel, hematology panel, and
           coagulation panel)

        2. DAT and IAT

        3. Immune reactivity test for IBS RBC

        4. For SCD patients undergoing regular RCE:

             -  Complete blood count including Hb and reticulocytes; and proportion (%) of HbS,
                HbA, and HbF.

             -  Plasma frozen sample for determination of S-300 and GSH concentrations.

      All AEs, SAEs, TRs and unanticipated adverse device effects will be reviewed and recorded for
      the period from the first study transfusion through 28 days after the last study transfusion.

      End of Study Visit (Day 75 ±15 days) for all transfused patients:

      Day 75 (± 15 days) after the last study transfusion either in the initial 28-day acute
      transfusion period or after the extension period, a blood sample will be collected for a DAT
      and immune reactivity test for IBS RBC.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Adjusted hemoglobin increment
time frame: 15 minutes - 24 hours post transfusion
description: The difference between the pre-transfusion and post transfusion episode hemoglobin values divided by the total hemoglobin content transfused, averaged over one or more transfusion episodes in patients without active bleeding at baseline (active bleeding is defined as WHO Grade 3 or 4 bleeding)
measure: Adverse Events
time frame: 28 days
description: Proportion of patients with any treatment-emergent adverse events (AEs) possibly, probably, or definitely related to study RBC transfusion through 28 days after the last study transfusion.
measure: Treatment emergent antibodies
time frame: 75 days
description: The proportion of patients with treatment emergent antibodies with confirmed specificity to IBS RBCs
measure: Adjusted hemoglobin consumption
time frame: 211 Days
description: Defined as total hemoglobin mass transfused in grams divided by body weight in kg at baseline and duration of the study transfusion period in days (g/kg/day), in patients without active bleeding at baseline.
measure: HbA clearance
time frame: 211 days
description: HbA clearance in patients with SCD undergoing regular repeated RCE
measure: Adverse Events
time frame: 28 Days after last study transfusion
description: Treatment-emergent AEs
measure: Transfusion reactions related to study RBCs (test or control)
time frame: 28 Days after last study transfusion
description: Defined by the CDC National Healthcare Safety Network [NHSN] Hemovigilance Module protocol
measure: RBC allo-antigens
time frame: 28 days
description: Treatment-emergent immunization to RBC allo-antigens
measure: Mortality
time frame: 28 Days after last study transfusion
description: All-cause mortality
measure: Adverse Events of Special Interest (AESI)
time frame: 28 Days after last study RCE
description: Proportion of subjects with adverse events of special interest (AESI) through 28 days after the last study transfusion.
measure: S-300 and GSH plasma levels
time frame: 15 minutes to 4 hrs after RCE
description: S-300 and Glutathione (GSH) plasma levels
arm group label: INTERCEPT (Test)
arm group type: Experimental
description: Red blood cell components treated with the INTERCEPT Blood System for Red Blood Cells ordered and administered to study patients by their treating physicians according to the local standards of care
arm group label: Conventional (Control)
arm group type: Active Comparator
description: Conventional RBC components ordered and administered to study patients by their treating physicians according to the local standards of care
intervention type: Device
intervention name: INTERCEPT Blood System for Red Blood Cells
description: The pathogen reduction process begins with a unit of RBCs derived from whole blood that is separated according to local regulations and standard operating procedures at the Blood Centers. RBCs are suspended in AS-5 or SAG-M for non-US sites. Leukocyte-reduction of whole blood or RBCs will be performed per manufacturer's instructions. The INTERCEPT Blood System process is performed on a single unit of leukocyte-depleted RBC in AS-5.
arm group label: INTERCEPT (Test)
intervention type: Device
intervention name: Conventional (Control)
description: Conventional RBC components ordered and administered to study patients by their treating physicians according to the local standards of care
arm group label: Conventional (Control)
criteria: 
gender: All
minimum age: 4 Years
maximum age: N/A
healthy volunteers: No
last name: Chris Marston
phone: 1-949-275-8702
email: cmarston@cerus.com
last name: Tino LoSicco, Ph.D
phone: 901-336-1353
email: tlosicco@cerus.com
facility: 
status: Recruiting
contact: 
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
facility: 
status: Active, not recruiting
country: Puerto Rico
country: United States
responsible party type: Sponsor
mesh term: Transfusion Reaction