Belimumab for the Treatment of Diffuse Cutaneous Systemic Sclerosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Hospital for Special Surgery, New York
Sponsor:
Collaborator:
Human Genome Sciences Inc.
Information provided by (Responsible Party):
Robert Spiera, MD, Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier:
NCT01670565
First received: August 15, 2012
Last updated: January 15, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Systemic Sclerosis
Drug: Belimumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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.

Resource links provided by NLM:


Further study details as provided by Hospital for Special Surgery, New York:

Primary Outcome Measures:
  • Change in Modified Rodnan Skin Score [ Time Frame: At 48 weeks ] [ Designated as safety issue: No ]
    The efficacy of the drug will be measured as the change in the Modified Rodnan Skin Score (MRSS) at 48 weeks. MRSS is a measurement of the degree of skin disease in systemic sclerosis where 17 areas of skin are rated by the examiner.

  • Number of Participants with Adverse and Serious Adverse Events [ Time Frame: At 52 weeks ] [ Designated as safety issue: Yes ]
    The safety and tolerability of belimumab in patients with systemic sclerosis will be as assessed by comparing the rates of adverse and serious adverse events between treatment and placebo groups.


Secondary Outcome Measures:
  • Change in Pulmonary Function Test Measures [ Time Frame: At 24 and 48 weeks ] [ Designated as safety issue: No ]
    This endpoint would measure the change in forced vital capacity and diffusion capacity of the pulmonary function test (the breathing test)

  • Change in the Medsger Severity Scale [ Time Frame: At 24 and 48 weeks ] [ Designated as safety issue: No ]
    This Medsger Severity Scale(MSS)is an objective method of assessing disease severity in patients with systemic sclerosis.

  • Change in the Scleroderma Health Assessment Questionnaire, Short Form-36, and Raynaud's Condition Score [ Time Frame: At each visit ] [ Designated as safety issue: No ]
    The Scleroderma Health Assessment Questionnaire (SHAQ) is a patient survey which indexes the participants degree of disability. The Short Form-36 is a questionnaire that addresses the patient's health-related quality of life. The Raynaud's Condition Score is a measure of the degree to which the patient's Raynaud's affects his or her daily functioning.


Estimated Enrollment: 20
Study Start Date: August 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mycophenolate mofetil + Belimumab
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.
Drug: 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.
Other Name: Benlysta
Placebo Comparator: Mycophenolate Mofetil + Saline (placebo)
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.

Detailed Description:

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.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age greater than or equal to eighteen years.
  2. Clinical diagnosis of diffuse systemic sclerosis by ACR criteria, with a stable modified Rodnan skin score in the one month preceding introduction of belimumab therapy.
  3. Disease duration of less than or equal to 3 years as defined by the date of onset of the first non-Raynaud's symptom.

Exclusion Criteria:

  1. Inability to render informed consent in accordance with institutional guidelines.
  2. Disease duration of greater than 3 years.
  3. Patients with mixed connective tissue disease or "overlap" (i.e. those who satisfy more than one set of ACR criteria for a rheumatic disease.)
  4. Limited scleroderma.
  5. Systemic sclerosis-like illness associated with environmental or ingested agents such as toxic rapeseed oil, vinyl chloride, or bleomycin.
  6. Ongoing treatment with immunosuppressive therapies including cyclophosphamide, azathioprine, methotrexate, or cyclosporine, or use of those medications within 1 month of trial entry.
  7. The use of other anti-fibrotic agents including colchicine, D-penicillamine, minocycline, tyrosine kinase inhibitors (nilotinib, imatinib, dasatinib), or Type 1 oral Collagen in the month prior to enrollment.
  8. Use in the prior month of corticosteroids at doses exceeding the equivalent of prednisone 10 mg daily. Use of corticosteroid at < 10 mg of prednisone can continue during the course of the study.
  9. Treatment with MMF at a dose of ≥ 2 grams daily for > 3 months.
  10. Concurrent serious medical condition which in the opinion of the investigator makes the patient inappropriate for this study such as uncontrollable CHF, arrhythmia, severe pulmonary or systemic hypertension, severe GI involvement, hepatic impairment, serum creatinine of greater than 2.0, active infection, severe diabetes, unstable atherosclerotic cardiovascular disease, malignancy, HIV, or severe peripheral vascular disease.
  11. A positive pregnancy test at entry into this study.
  12. Men and women with reproductive potential will be required to use effective means of contraception through the course of the study, such as a tubal ligation or hysterectomy, condom or diaphragm used with a spermicide,or an intrauterine device (IUD). Approved hormonal contraceptives (such as birth control pills, patches, implants or injections) may interact with and reduce the effectiveness of MMF and thus, are not acceptable. Contraceptive measures such as Plan B (TM), sold for emergency use after unprotected sex, are not acceptable methods for routine use.
  13. Breastfeeding. Breastfeeding is contraindicated with the use of MMF.
  14. Participation in another clinical research study involving the evaluation of another investigational drug within ninety days of entry into this study.
  15. The presence of severe lung disease as defined by a diffusion capacity of less than 30% of predicted or requiring supplemental oxygen.
  16. History of HIV infection
  17. Known active bacterial, viral, fungal, mycobacterial, or other infection r any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of screening, or oral antibiotics within 2 weeks prior to screening
  18. Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  19. Prior use of Belimumab, Rituximab, or other B-Cell depleting therapies ever
  20. The use of other biologics including TNF inhibitors, abatacept, or tocilizumab within 1 month of enrollment [this is a safety issue]
  21. Patients with a history of severe depression, psychosis, or suicidal ideation will be excluded.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01670565

Contacts
Contact: Robert Spiera, MD 2127742048 spierar@hss.edu

Locations
United States, New York
Hospital for Special Surgery Recruiting
New York, New York, United States, 10021
Contact: Daniele Lerner, BA    646-714-6302    lernerd@hss.edu   
Contact: Nina Paddu, BA    212-774-7194    paddun@hss.edu   
Principal Investigator: Robert Spiera, MD         
Sub-Investigator: Jessica Gordon, MD         
Sponsors and Collaborators
Hospital for Special Surgery, New York
Human Genome Sciences Inc.
Investigators
Principal Investigator: Robert Spiera, MD Hospital for Special Surgery, New York
  More Information

Additional Information:
No publications provided

Responsible Party: Robert Spiera, MD, Director of Scleroderma, Vasculitis and Myositis Center, Hospital for Special Surgery, New York
ClinicalTrials.gov Identifier: NCT01670565     History of Changes
Other Study ID Numbers: 12006
Study First Received: August 15, 2012
Last Updated: January 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Hospital for Special Surgery, New York:
Diffuse cutaneous systemic sclerosis
Early Diffuse cutaneous systemic sclerosis

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Sclerosis
Connective Tissue Diseases
Skin Diseases
Pathologic Processes
Mycophenolate mofetil
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 28, 2014