<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/NCT01670565</url>
  </required_header>
  <id_info>
    <org_study_id>2014-279</org_study_id>
    <nct_id>NCT01670565</nct_id>
  </id_info>
  <brief_title>Belimumab for the Treatment of Diffuse Cutaneous Systemic Sclerosis</brief_title>
  <official_title>Belimumab for the Treatment of Diffuse Cutaneous Systemic Sclerosis: A Phase 2a, Single-centered, Randomized, Placebo-controlled, Double-blind, Proof-of-concept Pilot Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Hospital for Special Surgery, New York</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Human Genome Sciences Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Hospital for Special Surgery, New York</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a 48 week, phase IIa, single center, randomized, double-blind, placebo-controlled,&#xD;
      proof-of-concept pilot study. All participants will first be treated with mycophenolate&#xD;
      mofetil (MMF, Cellcept) and titrated up to a dose of 2 grams/day. Following this period, half&#xD;
      will be given either a belimumab (Benlysta®) or placebo intravenous infusion to treat early&#xD;
      diffuse cutaneous systemic sclerosis. Belimumab/MMF is expected to improve disease activity&#xD;
      measured by an improvement in skin thickening and stability of pulmonary function test&#xD;
      measurements when compared to patients treated with placebo/MMF.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The specific objectives of this study are to:&#xD;
&#xD;
        1. Determine whether belimumab used in combination with MMF is safe and tolerable in the&#xD;
           treatment of patients with early diffuse cutaneous systemic sclerosis (Disease duration&#xD;
           &lt; 3 years).&#xD;
&#xD;
        2. Determine whether belimumab used in combination with MMF is more effective in the&#xD;
           treatment of diffuse cutaneous systemic sclerosis than MMF alone, as measured by change&#xD;
           in modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), hemoglobin corrected&#xD;
           diffusion capacity (DLCO), Medsger Severity Scale (MSS), and by other physician and&#xD;
           patient derived outcome measures.&#xD;
&#xD;
        3. Determine the biological activity of Belimumab/MMF as assessed by effect on histology of&#xD;
           skin, change in B-Cell profiles, effect on BLyS levels, and effect on serological and&#xD;
           cutaneous biomarkers of disease activity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2012</start_date>
  <completion_date type="Actual">February 2016</completion_date>
  <primary_completion_date type="Actual">November 2015</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Modified Rodnan Skin Score (MRSS)</measure>
    <time_frame>Baseline and at 52 weeks</time_frame>
    <description>Change in MRSS is measured by median change (and interquartile range) from Baseline median to week 52 median. The efficacy of the drug will be measured as the change in the Modified Rodnan Skin Score (MRSS) at 52 weeks. The Modified Rodnan Skin Score (MRSS) measures dermal skin thickness through the examination of 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (in pairs), and face, chest, and abdomen. The skin score is 0 for uninvolved skin through 3 for severe thickening (hidebound skin). The total skin score is the sum of the skin scores of the individual areas. The minimum score is 0 and the maximum score is 51. A higher score indicates greater severity of disease</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of Adverse Events and Serious Adverse Events</measure>
    <time_frame>At 52 weeks</time_frame>
    <description>The safety and tolerability of belimumab in patients with systemic sclerosis will be as assessed by comparing the rates of adverse events (AEs) and serious adverse events (SAEs) between treatment and placebo groups.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Forced Vital Capacity (FVC)</measure>
    <time_frame>Baseline and Week 52</time_frame>
    <description>Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking a deep breath. It is used to determine the severity of lung disease. FVC for a given individual is compared to reference or predicted values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. FVC % predicted compares the patients FVC values with the reference values. Results are considered normal if FVC is 80 percent or more of the predicted value. Change in FVC % predicted is measured by median change (and interquartile range) from Baseline median to week 52 median.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)</measure>
    <time_frame>Baseline and Week 52</time_frame>
    <description>Diffusing capacity of the lungs for carbon monoxide (DLCO) measures how much oxygen travels from the alveoli of the lungs to the blood stream. It is used to determine the severity of lung disease. DLCO for a given individual is compared to reference or predicted values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. DLCO % predicted compares the patients DLCO values with the reference values. An individuals DLCO result that is at least 80% of the predicted value is considered normal. Change in DLCO % predicted is measured by median change (and interquartile range) from Baseline median to week 52 median.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ DI)</measure>
    <time_frame>Baseline and Week 52</time_frame>
    <description>The Scleroderma Health Assessment Questionnaire (SHAQ) consist of the Health Assessment Questionnaire (HAQ) and 8 other domains addressing scleroderma related manifestations that contribute to disability. It is a quality of life measure. Each question is scored from 0 (without difficulty) to 3 (unable to do). Some domains in the SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale.&#xD;
The maximum from each category is added together and divided by the number of categories completed. The total scale range is 0-3. A higher score indicates worse functionality.&#xD;
Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) is measured as median change (and interquartile range) from Baseline median to week 52 median. The reported median change can range from -3 to 3. A negative median change indicates a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in in Short Form-36 (SF-36) Questionnaire:Mental Component Summary</measure>
    <time_frame>Baseline and at 52 weeks</time_frame>
    <description>The Short Form 36 (SF-36) is a validated 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The mental component score (MCS) is composed of a subset of the 8 health domains. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. The SF-36 mental component can be obtained by looking at the mean average of all the emotionally relevant items. Change in Short Form 36 mental (SF-36 MC) is measured by median change (and interquartile range) from Baseline to week 52. The median change can range from -100 to 100. A positive median change indicates indicates an improved outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Short Form-36 (SF-36) Questionnaire: Physical Component Summary</measure>
    <time_frame>Baseline and Week 52</time_frame>
    <description>The Short Form 36 (SF-36) is a 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The physical component score is composed of a subset of the 8 health domains.The SF-36 physical component can be obtained by looking at the mean average of all the physically relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. Change in Short Form 36 physical component (SF-36 PC) is measured by median change (and interquartile range) from Baseline to week 52. The median change can range from -100 to 100. A positive median change indicates indicates an improved outcome.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Systemic Sclerosis</condition>
  <arm_group>
    <arm_group_label>Mycophenolate mofetil + Belimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After the patient has been titrated to 2 grams of MMF per day, the patient will receive EITHER a 10 mg/kg belimumab (Benlysta) intravenous infusion OR a placebo (saline) infusion. This medication and infusion will of course be covered by the study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Mycophenolate Mofetil + Saline (placebo)</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Belimumab</intervention_name>
    <description>Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic sclerosis.</description>
    <arm_group_label>Mycophenolate mofetil + Belimumab</arm_group_label>
    <other_name>Benlysta</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Mycophenolate Mofetil</intervention_name>
    <description>Patients received background MMF therapy, some who were naive to MMF were titrated up to 1,000 mg twice daily and others had been receiving MMF at &lt;2,000 mg/day for &lt;3 months. MMF was chosen so that background therapy would be uniform and not a further source of variability in the small study.</description>
    <arm_group_label>Mycophenolate Mofetil + Saline (placebo)</arm_group_label>
    <arm_group_label>Mycophenolate mofetil + Belimumab</arm_group_label>
    <other_name>MMF, Cellcept</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo Infusion</intervention_name>
    <description>Infusion of normal saline</description>
    <arm_group_label>Mycophenolate Mofetil + Saline (placebo)</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age greater than or equal to eighteen years.&#xD;
&#xD;
          2. Clinical diagnosis of diffuse systemic sclerosis by ACR criteria, with a stable&#xD;
             modified Rodnan skin score in the one month preceding introduction of belimumab&#xD;
             therapy.&#xD;
&#xD;
          3. Disease duration of less than or equal to 3 years as defined by the date of onset of&#xD;
             the first non-Raynaud's symptom.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to render informed consent in accordance with institutional guidelines.&#xD;
&#xD;
          2. Disease duration of greater than 3 years.&#xD;
&#xD;
          3. Patients with mixed connective tissue disease or &quot;overlap&quot; (i.e. those who satisfy&#xD;
             more than one set of ACR criteria for a rheumatic disease.)&#xD;
&#xD;
          4. Limited scleroderma.&#xD;
&#xD;
          5. Systemic sclerosis-like illness associated with environmental or ingested agents such&#xD;
             as toxic rapeseed oil, vinyl chloride, or bleomycin.&#xD;
&#xD;
          6. Ongoing treatment with immunosuppressive therapies including cyclophosphamide,&#xD;
             azathioprine, methotrexate, or cyclosporine, or use of those medications within 1&#xD;
             month of trial entry.&#xD;
&#xD;
          7. The use of other anti-fibrotic agents including colchicine, D-penicillamine,&#xD;
             minocycline, tyrosine kinase inhibitors (nilotinib, imatinib, dasatinib), or Type 1&#xD;
             oral Collagen in the month prior to enrollment.&#xD;
&#xD;
          8. Use in the prior month of corticosteroids at doses exceeding the equivalent of&#xD;
             prednisone 10 mg daily. Use of corticosteroid at &lt; 10 mg of prednisone can continue&#xD;
             during the course of the study.&#xD;
&#xD;
          9. Treatment with MMF at a dose of ≥ 2 grams daily for &gt; 3 months.&#xD;
&#xD;
         10. Concurrent serious medical condition which in the opinion of the investigator makes&#xD;
             the patient inappropriate for this study such as uncontrollable CHF, arrhythmia,&#xD;
             severe pulmonary or systemic hypertension, severe GI involvement, hepatic impairment,&#xD;
             serum creatinine of greater than 2.0, active infection, severe diabetes, unstable&#xD;
             atherosclerotic cardiovascular disease, malignancy, HIV, or severe peripheral vascular&#xD;
             disease.&#xD;
&#xD;
         11. A positive pregnancy test at entry into this study.&#xD;
&#xD;
         12. Men and women with reproductive potential will be required to use effective means of&#xD;
             contraception through the course of the study, such as a tubal ligation or&#xD;
             hysterectomy, condom or diaphragm used with a spermicide,or an intrauterine device&#xD;
             (IUD). Approved hormonal contraceptives (such as birth control pills, patches,&#xD;
             implants or injections) may interact with and reduce the effectiveness of MMF and&#xD;
             thus, are not acceptable. Contraceptive measures such as Plan B (TM), sold for&#xD;
             emergency use after unprotected sex, are not acceptable methods for routine use.&#xD;
&#xD;
         13. Breastfeeding. Breastfeeding is contraindicated with the use of MMF.&#xD;
&#xD;
         14. Participation in another clinical research study involving the evaluation of another&#xD;
             investigational drug within ninety days of entry into this study.&#xD;
&#xD;
         15. The presence of severe lung disease as defined by a diffusion capacity of less than&#xD;
             30% of predicted or requiring supplemental oxygen.&#xD;
&#xD;
         16. History of HIV infection&#xD;
&#xD;
         17. Known active bacterial, viral, fungal, mycobacterial, or other infection r any major&#xD;
             episode of infection requiring hospitalization or treatment with IV antibiotics within&#xD;
             4 weeks of screening, or oral antibiotics within 2 weeks prior to screening&#xD;
&#xD;
         18. Any other disease, metabolic dysfunction, physical examination finding, or clinical&#xD;
             laboratory finding giving reasonable suspicion of a disease or condition that&#xD;
             contraindicates the use of an investigational drug or that may affect the&#xD;
             interpretation of the results or render the patient at high risk from treatment&#xD;
             complications&#xD;
&#xD;
         19. Prior use of Belimumab, Rituximab, or other B-Cell depleting therapies ever&#xD;
&#xD;
         20. The use of other biologics including TNF inhibitors, abatacept, or tocilizumab within&#xD;
             1 month of enrollment [this is a safety issue]&#xD;
&#xD;
         21. Patients with a history of severe depression, psychosis, or suicidal ideation will be&#xD;
             excluded.&#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>Robert Spiera, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Hospital for Special Surgery, New York</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hospital for Special Surgery</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.hss.edu/scleroderma-vasculitis-center.asp</url>
    <description>Scleroderma, Vasculitis, &amp; Myositis Center Website</description>
  </link>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 20, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 22, 2012</study_first_posted>
  <results_first_submitted>January 10, 2018</results_first_submitted>
  <results_first_submitted_qc>May 20, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">May 24, 2022</results_first_posted>
  <last_update_submitted>May 20, 2022</last_update_submitted>
  <last_update_submitted_qc>May 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Diffuse cutaneous systemic sclerosis</keyword>
  <keyword>Early Diffuse cutaneous systemic sclerosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Scleroderma, Systemic</mesh_term>
    <mesh_term>Scleroderma, Diffuse</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Mycophenolic Acid</mesh_term>
    <mesh_term>Belimumab</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Mycophenolate Mofetil + Belimumab</title>
          <description>Patients in this arm will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice titrated to 2 grams of MMF per day, followed by 10 mg/kg belimumab (Benlysta). Belimumab Infusion will be administered 14 times over a period of 48 weeks. MMF will be administered through 48 weeks.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic sclerosis.</description>
        </group>
        <group group_id="P2">
          <title>Mycophenolate Mofetil + Saline (Placebo)</title>
          <description>Patients in this arm will FIRST receive MMF alone followed by normal saline infusion that appears identical to the belimumab infusion. Saline Infusion will be administered 14 times over a period of 48 weeks. MMF will be administered through 48 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Mycophenolate Mofetil + Belimumab</title>
          <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After the patient has been titrated to 2 grams of MMF per day, the patient will receive EITHER a 10 mg/kg belimumab (Benlysta) intravenous infusion OR placebo (saline) infusion. This medication and infusion will be covered by the study.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic sclerosis.</description>
        </group>
        <group group_id="B2">
          <title>Mycophenolate Mofetil + Saline (Placebo)</title>
          <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.</description>
        </group>
        <group group_id="B3">
          <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="10"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53" spread="12.1"/>
                    <measurement group_id="B2" value="56.7" spread="10.26"/>
                    <measurement group_id="B3" value="54.85" spread="11.18"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </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_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Interstitial Lung Disease (ILD)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Anti-Scl-70</title>
          <description>Characteristics of the patients at baseline. Number and percent of participants in each group who were positive for anti-Scl-70. The presence of anti-Scl-70 antibodies increases the risk for diffuse skin involvement and scleroderma related lung disease.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Anti- RNA Pol III</title>
          <description>Characteristics of the patients at baseline. Number and percent of participants in each group who were positive for Anti-RNA polymerase III. Numerous studies have shown that systemic sclerosis patients with anti-RNA polymerase III have an increased risk of the diffuse cutaneous form of scleroderma.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="10"/>
                    <count group_id="B2" value="10"/>
                    <count group_id="B3" value="20"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Modified Rodnan Skin Score (MRSS) at baseline</title>
          <description>The Modified Rodnan Skin Score (MRSS) measures dermal skin thickness through the examination of 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (in pairs), and face, chest, and abdomen. The skin score is 0 for uninvolved skin through 3 for severe thickening (hidebound skin). The total skin score is the sum of the skin scores of the individual areas. The minimum score is 0 and the maximum score is 51. A higher score indicates greater severity of disease.</description>
          <population>MRSS values are given for treated patients (n=9 per group) and not for all patients randomized (n=10 per group)</population>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="27" lower_limit="26.5" upper_limit="31"/>
                    <measurement group_id="B2" value="28" lower_limit="22" upper_limit="28"/>
                    <measurement group_id="B3" value="27" lower_limit="22" upper_limit="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Forced Vital Capacity (FVC)</title>
          <description>FVC % predicted at baseline. Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking a deep breath. It is used to determine the severity of lung disease. FVC for a given individual is compared to reference or predicted values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. FVC % predicted compares the patients FVC values with the reference values.</description>
          <population>Values for treated patients such as FVC% predicted and DLCO% predicted are given for treated patients (n=9 per group) and not for all patients randomized (n=10).</population>
          <units>% predicted</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="88" lower_limit="81" upper_limit="100"/>
                    <measurement group_id="B2" value="95" lower_limit="88" upper_limit="101"/>
                    <measurement group_id="B3" value="94.5" lower_limit="81" upper_limit="101"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Diffusing capacity of the lungs for carbon monoxide</title>
          <description>Diffusing capacity of the lungs for carbon monoxide (DLCO) measures how much oxygen travels from the alveoli of the lungs to the blood stream. It is used to determine the severity of lung disease. DLCO for a given individual is compared to reference values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. DLCO % predicted compares the patients DLCO values with the reference values. An individuals DLCO result that is at least 80% of the predicted value is considered normal.</description>
          <population>Values for treated patients such as FVC% predicted and DLCO% predicted are given for treated patients (n=9 per group) and not for all patients randomized (n=10).</population>
          <units>% predicted</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="9"/>
                    <count group_id="B2" value="9"/>
                    <count group_id="B3" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="85" lower_limit="67" upper_limit="94"/>
                    <measurement group_id="B2" value="81" lower_limit="81" upper_limit="87"/>
                    <measurement group_id="B3" value="83" lower_limit="67" upper_limit="92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Modified Rodnan Skin Score (MRSS)</title>
        <description>Change in MRSS is measured by median change (and interquartile range) from Baseline median to week 52 median. The efficacy of the drug will be measured as the change in the Modified Rodnan Skin Score (MRSS) at 52 weeks. The Modified Rodnan Skin Score (MRSS) measures dermal skin thickness through the examination of 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (in pairs), and face, chest, and abdomen. The skin score is 0 for uninvolved skin through 3 for severe thickening (hidebound skin). The total skin score is the sum of the skin scores of the individual areas. The minimum score is 0 and the maximum score is 51. A higher score indicates greater severity of disease</description>
        <time_frame>Baseline and at 52 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mycophenolate Mofetil + Belimumab</title>
            <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a 10 mg/kg belimumab (Benlysta) intravenous infusion infusion.This medication and infusion will of course be covered by the study.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic</description>
          </group>
          <group group_id="O2">
            <title>Mycophenolate Mofetil + Saline (Placebo)</title>
            <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.&#xD;
All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a placebo (saline) infusion.This infusion will of course be covered by the study.&#xD;
.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Modified Rodnan Skin Score (MRSS)</title>
          <description>Change in MRSS is measured by median change (and interquartile range) from Baseline median to week 52 median. The efficacy of the drug will be measured as the change in the Modified Rodnan Skin Score (MRSS) at 52 weeks. The Modified Rodnan Skin Score (MRSS) measures dermal skin thickness through the examination of 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (in pairs), and face, chest, and abdomen. The skin score is 0 for uninvolved skin through 3 for severe thickening (hidebound skin). The total skin score is the sum of the skin scores of the individual areas. The minimum score is 0 and the maximum score is 51. A higher score indicates greater severity of disease</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10" lower_limit="-13" upper_limit="-9"/>
                    <measurement group_id="O2" value="-3.0" lower_limit="-15" upper_limit="-1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Number of Adverse Events and Serious Adverse Events</title>
        <description>The safety and tolerability of belimumab in patients with systemic sclerosis will be as assessed by comparing the rates of adverse events (AEs) and serious adverse events (SAEs) between treatment and placebo groups.</description>
        <time_frame>At 52 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mycophenolate Mofetil + Belimumab</title>
            <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a 10 mg/kg belimumab (Benlysta) intravenous infusion infusion.This medication and infusion will of course be covered by the study.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic</description>
          </group>
          <group group_id="O2">
            <title>Mycophenolate Mofetil + Saline (Placebo)</title>
            <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.&#xD;
All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a placebo (saline) infusion.This infusion will of course be covered by the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Adverse Events and Serious Adverse Events</title>
          <description>The safety and tolerability of belimumab in patients with systemic sclerosis will be as assessed by comparing the rates of adverse events (AEs) and serious adverse events (SAEs) between treatment and placebo groups.</description>
          <units>number of AEs</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="10"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Total number of AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="53"/>
                    <measurement group_id="O2" value="56"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Total number of infectious AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Serious AEs</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Forced Vital Capacity (FVC)</title>
        <description>Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking a deep breath. It is used to determine the severity of lung disease. FVC for a given individual is compared to reference or predicted values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. FVC % predicted compares the patients FVC values with the reference values. Results are considered normal if FVC is 80 percent or more of the predicted value. Change in FVC % predicted is measured by median change (and interquartile range) from Baseline median to week 52 median.</description>
        <time_frame>Baseline and Week 52</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mycophenolate Mofetil + Belimumab</title>
            <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a 10 mg/kg belimumab (Benlysta) intravenous infusion infusion.This medication and infusion will of course be covered by the study.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic</description>
          </group>
          <group group_id="O2">
            <title>Mycophenolate Mofetil + Saline (Placebo)</title>
            <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.&#xD;
All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a placebo (saline) infusion.This infusion will of course be covered by the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Forced Vital Capacity (FVC)</title>
          <description>Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking a deep breath. It is used to determine the severity of lung disease. FVC for a given individual is compared to reference or predicted values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. FVC % predicted compares the patients FVC values with the reference values. Results are considered normal if FVC is 80 percent or more of the predicted value. Change in FVC % predicted is measured by median change (and interquartile range) from Baseline median to week 52 median.</description>
          <units>% predicted</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.00" lower_limit="0.00" upper_limit="8.00"/>
                    <measurement group_id="O2" value="-2.00" lower_limit="-6.00" upper_limit="4.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)</title>
        <description>Diffusing capacity of the lungs for carbon monoxide (DLCO) measures how much oxygen travels from the alveoli of the lungs to the blood stream. It is used to determine the severity of lung disease. DLCO for a given individual is compared to reference or predicted values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. DLCO % predicted compares the patients DLCO values with the reference values. An individuals DLCO result that is at least 80% of the predicted value is considered normal. Change in DLCO % predicted is measured by median change (and interquartile range) from Baseline median to week 52 median.</description>
        <time_frame>Baseline and Week 52</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mycophenolate Mofetil + Belimumab</title>
            <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, the patient will receive a 10 mg/kg belimumab (Benlysta) intravenous infusion.This medication and infusion will of course be covered by the study.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic</description>
          </group>
          <group group_id="O2">
            <title>Mycophenolate Mofetil + Saline (Placebo)</title>
            <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.&#xD;
All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a placebo (saline) infusion.This infusion will of course be covered by the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)</title>
          <description>Diffusing capacity of the lungs for carbon monoxide (DLCO) measures how much oxygen travels from the alveoli of the lungs to the blood stream. It is used to determine the severity of lung disease. DLCO for a given individual is compared to reference or predicted values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. DLCO % predicted compares the patients DLCO values with the reference values. An individuals DLCO result that is at least 80% of the predicted value is considered normal. Change in DLCO % predicted is measured by median change (and interquartile range) from Baseline median to week 52 median.</description>
          <units>% predicted</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.00" lower_limit="-7.00" upper_limit="7.00"/>
                    <measurement group_id="O2" value="0.00" lower_limit="-6.00" upper_limit="7.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ DI)</title>
        <description>The Scleroderma Health Assessment Questionnaire (SHAQ) consist of the Health Assessment Questionnaire (HAQ) and 8 other domains addressing scleroderma related manifestations that contribute to disability. It is a quality of life measure. Each question is scored from 0 (without difficulty) to 3 (unable to do). Some domains in the SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale.&#xD;
The maximum from each category is added together and divided by the number of categories completed. The total scale range is 0-3. A higher score indicates worse functionality.&#xD;
Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) is measured as median change (and interquartile range) from Baseline median to week 52 median. The reported median change can range from -3 to 3. A negative median change indicates a better outcome.</description>
        <time_frame>Baseline and Week 52</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mycophenolate Mofetil + Belimumab</title>
            <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, the patient will receive a 10 mg/kg belimumab (Benlysta) intravenous infusion.This medication and infusion will of course be covered by the study.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic</description>
          </group>
          <group group_id="O2">
            <title>Mycophenolate Mofetil + Saline (Placebo)</title>
            <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.&#xD;
All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a placebo (saline) infusion.This infusion will of course be covered by the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ DI)</title>
          <description>The Scleroderma Health Assessment Questionnaire (SHAQ) consist of the Health Assessment Questionnaire (HAQ) and 8 other domains addressing scleroderma related manifestations that contribute to disability. It is a quality of life measure. Each question is scored from 0 (without difficulty) to 3 (unable to do). Some domains in the SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale.&#xD;
The maximum from each category is added together and divided by the number of categories completed. The total scale range is 0-3. A higher score indicates worse functionality.&#xD;
Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) is measured as median change (and interquartile range) from Baseline median to week 52 median. The reported median change can range from -3 to 3. A negative median change indicates a better outcome.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.25" lower_limit="-0.38" upper_limit="-0.25"/>
                    <measurement group_id="O2" value="0.00" lower_limit="-0.13" upper_limit="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in in Short Form-36 (SF-36) Questionnaire:Mental Component Summary</title>
        <description>The Short Form 36 (SF-36) is a validated 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The mental component score (MCS) is composed of a subset of the 8 health domains. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. The SF-36 mental component can be obtained by looking at the mean average of all the emotionally relevant items. Change in Short Form 36 mental (SF-36 MC) is measured by median change (and interquartile range) from Baseline to week 52. The median change can range from -100 to 100. A positive median change indicates indicates an improved outcome.</description>
        <time_frame>Baseline and at 52 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mycophenolate Mofetil + Belimumab</title>
            <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, the patient will receive a 10 mg/kg belimumab (Benlysta) intravenous infusion.This medication and infusion will of course be covered by the study.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic</description>
          </group>
          <group group_id="O2">
            <title>Mycophenolate Mofetil + Saline (Placebo)</title>
            <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.&#xD;
All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a placebo (saline) infusion.This infusion will of course be covered by the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in in Short Form-36 (SF-36) Questionnaire:Mental Component Summary</title>
          <description>The Short Form 36 (SF-36) is a validated 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The mental component score (MCS) is composed of a subset of the 8 health domains. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. The SF-36 mental component can be obtained by looking at the mean average of all the emotionally relevant items. Change in Short Form 36 mental (SF-36 MC) is measured by median change (and interquartile range) from Baseline to week 52. The median change can range from -100 to 100. A positive median change indicates indicates an improved outcome.</description>
          <units>score on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.50" lower_limit="2.50" upper_limit="18.50"/>
                    <measurement group_id="O2" value="3.00" lower_limit="0.00" upper_limit="10.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Short Form-36 (SF-36) Questionnaire: Physical Component Summary</title>
        <description>The Short Form 36 (SF-36) is a 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The physical component score is composed of a subset of the 8 health domains.The SF-36 physical component can be obtained by looking at the mean average of all the physically relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. Change in Short Form 36 physical component (SF-36 PC) is measured by median change (and interquartile range) from Baseline to week 52. The median change can range from -100 to 100. A positive median change indicates indicates an improved outcome.</description>
        <time_frame>Baseline and Week 52</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Mycophenolate Mofetil + Belimumab</title>
            <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, the patient will receive a 10 mg/kg belimumab (Benlysta) intravenous infusion.This medication and infusion will of course be covered by the study.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic</description>
          </group>
          <group group_id="O2">
            <title>Mycophenolate Mofetil + Saline (Placebo)</title>
            <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.&#xD;
All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a placebo (saline) infusion.This infusion will of course be covered by the study.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Short Form-36 (SF-36) Questionnaire: Physical Component Summary</title>
          <description>The Short Form 36 (SF-36) is a 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The physical component score is composed of a subset of the 8 health domains.The SF-36 physical component can be obtained by looking at the mean average of all the physically relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. Change in Short Form 36 physical component (SF-36 PC) is measured by median change (and interquartile range) from Baseline to week 52. The median change can range from -100 to 100. A positive median change indicates indicates an improved outcome.</description>
          <units>scores on a scale, 0-100</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.00" lower_limit="-3.50" upper_limit="19.00"/>
                    <measurement group_id="O2" value="-3.00" lower_limit="-3.00" upper_limit="27.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Mycophenolate Mofetil + Belimumab</title>
          <description>All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, the patient will receive a 10 mg/kg belimumab (Benlysta) intravenous infusion. This medication and infusion will be covered by the study.&#xD;
Belimumab: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic sclerosis.</description>
        </group>
        <group group_id="E2">
          <title>Mycophenolate Mofetil + Saline (Placebo)</title>
          <description>In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.&#xD;
All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After being titrated to 2 grams of MMF per day, patients in this experimental group will receive a placebo (saline) infusion.This infusion will of course be covered by the study.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>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="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest Pain</sub_title>
                <description>related to progression of SSc-related cardiomyopathy</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety Attack</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Dyspnea</sub_title>
                <description>related to progression of SSc-related cardiomyopathy</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>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="9" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="9" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Hemoglobin A1c Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>CPK Increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hyperglycemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Chest-Pain Cardiac</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Otitis Media</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred Vision</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Conjunctival Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Gastroesophageal Refluex Disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Irritable Bowel</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Allergic Reaction (Infusion)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>ALT Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>AST Increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Oral Hemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tooth Mobility</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Non-cardiac chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Syncope</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Lymphocyte count decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>IgM Decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Zoster</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lip infection (HSV-1)</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Infections and Infestations -Other (H Pylori, Stomach)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Infections and Infestations -Other (Viral Syndrome)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Laryngeal Inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Salivary Gland Infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Lung Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Soft Tissue Infection (wart)</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Anemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Weight Loss</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pain in Extremity</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Arthralgia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Arthritis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Generalized Muscle Weakness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Meniscal Tear</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Acroosteolysis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Calcinosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Myalgia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Back Pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Fracture (Shoulder)</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Squamous Cell Carcinoma</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Memory Impairment-acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Neuralgia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="3" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Anxiety (Acute)</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" events="6" subjects_affected="3" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Asymptomatic Bacteriuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cystitis noninfective</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Hermaturia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Reproductive system and breast disorders</title>
            <event_list>
              <event>
                <sub_title>Testicular Disorder (hydrocele)</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Irregular Menstruation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Vaginal Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Upper Respiratory Infection</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Pulmonary Nodule Benign</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash Acneiform</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Contact Dermatitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Skin Ulceration (Leg)</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Aortic Valve Disease (progression)</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>Annel Fernandez</name_or_title>
      <organization>Hospital For Special Surgery</organization>
      <phone>212 774 2123</phone>
      <email>fernandeza@hss.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/NCT01670565
org study id: 2014-279
nct id: NCT01670565
lead sponsor: 
collaborator: 
has dmc: Yes
This is a 48 week, phase IIa, single center, randomized, double-blind, placebo-controlled,
      proof-of-concept pilot study. All participants will first be treated with mycophenolate
      mofetil (MMF, Cellcept) and titrated up to a dose of 2 grams/day. Following this period, half
      will be given either a belimumab (Benlysta®) or placebo intravenous infusion to treat early
      diffuse cutaneous systemic sclerosis. Belimumab/MMF is expected to improve disease activity
      measured by an improvement in skin thickening and stability of pulmonary function test
      measurements when compared to patients treated with placebo/MMF.
The specific objectives of this study are to:

        1. Determine whether belimumab used in combination with MMF is safe and tolerable in the
           treatment of patients with early diffuse cutaneous systemic sclerosis (Disease duration
           < 3 years).

        2. Determine whether belimumab used in combination with MMF is more effective in the
           treatment of diffuse cutaneous systemic sclerosis than MMF alone, as measured by change
           in modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), hemoglobin corrected
           diffusion capacity (DLCO), Medsger Severity Scale (MSS), and by other physician and
           patient derived outcome measures.

        3. Determine the biological activity of Belimumab/MMF as assessed by effect on histology of
           skin, change in B-Cell profiles, effect on BLyS levels, and effect on serological and
           cutaneous biomarkers of disease activity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Change in Modified Rodnan Skin Score (MRSS)
time frame: Baseline and at 52 weeks
description: Change in MRSS is measured by median change (and interquartile range) from Baseline median to week 52 median. The efficacy of the drug will be measured as the change in the Modified Rodnan Skin Score (MRSS) at 52 weeks. The Modified Rodnan Skin Score (MRSS) measures dermal skin thickness through the examination of 17 body areas: fingers, hands, forearms, arms, feet, legs, and thighs (in pairs), and face, chest, and abdomen. The skin score is 0 for uninvolved skin through 3 for severe thickening (hidebound skin). The total skin score is the sum of the skin scores of the individual areas. The minimum score is 0 and the maximum score is 51. A higher score indicates greater severity of disease
measure: Number of Adverse Events and Serious Adverse Events
time frame: At 52 weeks
description: The safety and tolerability of belimumab in patients with systemic sclerosis will be as assessed by comparing the rates of adverse events (AEs) and serious adverse events (SAEs) between treatment and placebo groups.
measure: Change in Forced Vital Capacity (FVC)
time frame: Baseline and Week 52
description: Forced vital capacity (FVC) is the amount of air that can be forcibly exhaled from the lungs after taking a deep breath. It is used to determine the severity of lung disease. FVC for a given individual is compared to reference or predicted values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. FVC % predicted compares the patients FVC values with the reference values. Results are considered normal if FVC is 80 percent or more of the predicted value. Change in FVC % predicted is measured by median change (and interquartile range) from Baseline median to week 52 median.
measure: Change in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
time frame: Baseline and Week 52
description: Diffusing capacity of the lungs for carbon monoxide (DLCO) measures how much oxygen travels from the alveoli of the lungs to the blood stream. It is used to determine the severity of lung disease. DLCO for a given individual is compared to reference or predicted values. The reference values are based on healthy individuals with normal lung function and indicates values that would be expected for someone of the same sex, age and height. DLCO % predicted compares the patients DLCO values with the reference values. An individuals DLCO result that is at least 80% of the predicted value is considered normal. Change in DLCO % predicted is measured by median change (and interquartile range) from Baseline median to week 52 median.
measure: Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ DI)
time frame: Baseline and Week 52
description: The Scleroderma Health Assessment Questionnaire (SHAQ) consist of the Health Assessment Questionnaire (HAQ) and 8 other domains addressing scleroderma related manifestations that contribute to disability. It is a quality of life measure. Each question is scored from 0 (without difficulty) to 3 (unable to do). Some domains in the SHAQ are visual analog scales that are measured first and then changed to a 0-3 scale.
The maximum from each category is added together and divided by the number of categories completed. The total scale range is 0-3. A higher score indicates worse functionality.
Change in Scleroderma Health Assessment Questionnaire Disability Index (SHAQ-DI) is measured as median change (and interquartile range) from Baseline median to week 52 median. The reported median change can range from -3 to 3. A negative median change indicates a better outcome.
measure: Change in in Short Form-36 (SF-36) Questionnaire:Mental Component Summary
time frame: Baseline and at 52 weeks
description: The Short Form 36 (SF-36) is a validated 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The mental component score (MCS) is composed of a subset of the 8 health domains. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. The SF-36 mental component can be obtained by looking at the mean average of all the emotionally relevant items. Change in Short Form 36 mental (SF-36 MC) is measured by median change (and interquartile range) from Baseline to week 52. The median change can range from -100 to 100. A positive median change indicates indicates an improved outcome.
measure: Change in Short Form-36 (SF-36) Questionnaire: Physical Component Summary
time frame: Baseline and Week 52
description: The Short Form 36 (SF-36) is a 36 item questionnaire which measures quality of life across eight domains: physical functioning, role limitations due to physical health, role limitations due to emotional problems, energy/fatigue, emotional well-being, social functioning, pain, general health. The physical component score is composed of a subset of the 8 health domains.The SF-36 physical component can be obtained by looking at the mean average of all the physically relevant items. Each component is directly transformed into a 0 to 100 scale on the assumption that each question carries equal weight. A score of 0 is equal to maximum disability, and a score of 100 is equivalent to no disability. Change in Short Form 36 physical component (SF-36 PC) is measured by median change (and interquartile range) from Baseline to week 52. The median change can range from -100 to 100. A positive median change indicates indicates an improved outcome.
arm group label: Mycophenolate mofetil + Belimumab
arm group type: Experimental
description: All patients who enroll in this trial will FIRST receive mycophenolate mofetil (MMF, Cellcept), which is a drug commonly given to patients with scleroderma in clinical practice. This drug will be given at no cost to the patient. After the patient has been titrated to 2 grams of MMF per day, the patient will receive EITHER a 10 mg/kg belimumab (Benlysta) intravenous infusion OR a placebo (saline) infusion. This medication and infusion will of course be covered by the study.
arm group label: Mycophenolate Mofetil + Saline (placebo)
arm group type: Placebo Comparator
description: In order to observe the difference between belimumab/MMF compared to MMF alone, half of the patients will receive a normal saline infusion that appears identical to the belimumab infusion.
intervention type: Drug
intervention name: Belimumab
description: Belimumab (Benlysta®) decreases B-Cell survival and has been FDA approved for the treatment of systemic lupus erythematosus, another rheumatic autoimmune disease. Belimumab is a recombinant, fully human monoclonal antibody; it binds to the soluble human B lymphocyte stimulator (BLyS) with high affinity and inhibits its biologic activity. Prior research provides a robust rationale for the investigation of belimumab in combination with MMF (Cellcept ®) for the treatment of early diffuse cutaneous systemic sclerosis.
arm group label: Mycophenolate mofetil + Belimumab
other name: Benlysta
intervention type: Drug
intervention name: Mycophenolate Mofetil
description: Patients received background MMF therapy, some who were naive to MMF were titrated up to 1,000 mg twice daily and others had been receiving MMF at <2,000 mg/day for <3 months. MMF was chosen so that background therapy would be uniform and not a further source of variability in the small study.
arm group label: Mycophenolate Mofetil + Saline (placebo)
arm group label: Mycophenolate mofetil + Belimumab
other name: MMF, Cellcept
intervention type: Other
intervention name: Placebo Infusion
description: Infusion of normal saline
arm group label: Mycophenolate Mofetil + Saline (placebo)
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Robert Spiera, MD
role: Principal Investigator
affiliation: Hospital for Special Surgery, New York
facility: 
country: United States
url: http://www.hss.edu/scleroderma-vasculitis-center.asp
description: Scleroderma, Vasculitis, & Myositis Center Website
responsible party type: Sponsor
mesh term: Scleroderma, Systemic
mesh term: Scleroderma, Diffuse
mesh term: Sclerosis
mesh term: Mycophenolic Acid
mesh term: Belimumab
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 