Clinical trial NCT01670565
Conditions: Systemic Sclerosis
Keywords: Diffuse cutaneous systemic sclerosis Early Diffuse cutaneous systemic sclerosis
Sponsor: Hospital for Special Surgery, New York
Start date: 2012-08-01; Completion date: 2016-02-01
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

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.

Arms: arm 1: 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 2: 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.
Interventions: intervention 1: Belimumab intervention 2: Mycophenolate Mofetil intervention 3: Placebo Infusion
Intervention descriptions: intervention 1: 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. intervention 2: 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. intervention 3: Infusion of normal saline

Protocol documents: