A Randomized, Double-Blind, Placebo-Controlled, Phase II Multicenter Trial of a Monoclonal Antibody to CD20 (Rituximab) for the Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH)
Systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) is a serious, life-threatening manifestation of systemic sclerosis (SSc), an autoimmune disease of the connective tissue characterized by scarring (fibrosis) and atrophy of the skin, joints and tendons, skeletal muscles, and internal organs, and immunological disturbances. One-year survival for patients with SSc-PAH ranges from 50-81%. There is currently no cure for SSc-PAH and treatment is limited to vasodilator therapy used in all forms of PAH. In recent studies, immunotherapy was shown to be effective in treating SSc-interstitial lung disease, another serious, life-threatening manifestation of SSc. In addition, there are compelling pre-clinical data and anecdotal clinical reports that suggest modulation of the immune system may be an effective strategy for treating SSc-PAH. To test this approach, this trial will determine if rituximab, an immunotherapy, has a marked beneficial effect on clinical disease progression, with minimal toxicity, in patients with SSc-PAH when compared to placebo.
- biological : Rituximab
- other : Placebo
Phase: Phase 2
Ages Eligible For Study:
- Subject has provided written informed consent. - Subject must be between the ages of 18 and 75. - Clinical diagnosis of systemic sclerosis (either limited or diffuse cutaneous disease). - Diagnosis of SSc-PAH within the past 5 years, with a mean pulmonary arterial pressure of ? 25 mmHg at entry. - Mean Pulmonary Vascular Resistance (PVR) of > 3 Wood units. - Screening 6-minute Walking Distance (6MWD) of at least 100 meters. - New York Heart Association (NYHA) Functional Class II, III, or IV. - Subject must be able to maintain O2 saturation ? 90% at rest (with or without oxygen). Oxygen use is permitted. - Subject must be vaccinated with the pneumococcal vaccine at least one month prior to initiation of therapy, unless subject was vaccinated within 5 years of study entry. - Subject must have been treated with background medical therapy for PAH (prostanoid, endothelin receptor antagonist, PDE-5 inhibitor, and/or guanylate cyclase stimulators) for a minimum of 8 weeks and have been on stable dose medical therapy for at least 4 weeks prior to randomization with no expectation of change for 24 weeks after randomization.