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) ( Protocol # ASC01)

Study ID
STU 082010-287

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Megha Sharma
214-645-6489
megha.sharma@utsouthwestern.edu

Principal Investigator
Fernando Torres

Summary

eighty adults between the ages of 18 and 70 who have been diagnosed with SSc-PaH within the past 3 years and meet all entry criteria will be enrolled in this study, ten of those subjects at uT Southwestern medical center. Participants will receive 2 infusions (1000 mg) of either rituximab or placebo 14 days apart. The total duration of the study is anticipated to be approximately 3 years, allowing approximately 24 months for recruitment and 12 months for follow-up of each subject.

This study will compare patients treated with rituximab to those on placebo for change in pulmonary vascular resistance (PVR). The secondary objectives of this study are to compare treatment groups for other measures of clinical disease progression and to determine whether the effects on clinical disease progression are paralleled by changes in selected biomarkers. additionally, the safety and tolerability of rituximab for the treatment of SSc-PaH in patients receiving stable background medical treatment with prostanoid, endothelin receptor antagonist, and/or PDe-5 inhibitor therapy will be assessed.

Participant Eligibility

Subjects who meet all of the following criteria are eligible for enrollment into the study:
1. Subject has provided written informed consent.
2. Subject must be between the ages of 18 and 75 at the time of randomization.
3. Clinical diagnosis of systemic sclerosis (either limited or diffuse cutaneous disease).
4. Diagnosis of SSc-PAH within the past 5 years, with a mean pulmonary arterial pressure (mPAP) of >= 25 mmHg at entry.
5. Mean PVR of > 3 Wood units.
6. Screening 6MWD of at least 100 meters, but not more than 450 meters.
7. NYHA Functional Class II, III, or IV.
8. Subject must be able to maintain O2 saturation >= 90% at rest (with or without oxygen). Oxygen use is permitted.
9. 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. If vaccination occurred greater than 5 years prior to study entry, the subject must be revaccinated at least one month prior to initiation of therapy.
10. Subjects must have been treated with background medical therapy for PAH (prostanoid, endothelin receptor antagonist, and/or PDE-5 inhibitor) 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.