Belimumab for the Treatment of Diffuse Cutaneous Systemic Sclerosis
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.
|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.|
- 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.
- 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.
|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)|
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.
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.
The specific objectives of this study are to:
- 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).
- 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.
- 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.
|Contact: Robert Spiera, MDfirstname.lastname@example.org|
|United States, New York|
|Hospital for Special Surgery||Recruiting|
|New York, New York, United States, 10021|
|Contact: Daniele Lerner, BA 646-714-6302 email@example.com|
|Contact: Nina Paddu, BA 212-774-7194 firstname.lastname@example.org|
|Principal Investigator: Robert Spiera, MD|
|Sub-Investigator: Jessica Gordon, MD|
|Principal Investigator:||Robert Spiera, MD||Hospital for Special Surgery, New York|