Rituximab for Treatment of Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH)

Summary

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.

Conditions

• Systemic Sclerosis-Associated PAH

Interventions

BIOLOGICAL

Rituximab

Participants receive rituximab intravenous (IV) infusions, 1000 mg each, 14 days apart (Day 0 and Week 2). Rituximab is supplied as a sterile, clear, colorless, preservative-free liquid concentrate for intravenous (IV) administration in either 100 mg (10 mL) or 500 mg (50 mL) single-use vials, which must be diluted before administration Standard rituximab pre-medications will be provided in preparation for the rituximab infusions.

OTHER

Placebo

Participants receive placebo intravenous (IV) infusions 14 days apart (Day 0 and Week 2). Standard pre-medications will be provided in preparation for the infusions.

DIAGNOSTIC_TEST

CMRI

Up to 20 participants from each treatment arm will be assessed by CMRI at Baseline and at Week 24.

DRUG

prednisone

Prednisone dose of 40 mg (or equivalent) by mouth administered the night before and the morning of each study drug infusion.

DRUG

methylprednisolone

Methylprednisolone (or equivalent corticosteroid) administered intravenously 30 minutes prior to each study drug infusion.

DRUG

diphenhydramine

Diphenhydramine 50 mg (or equivalent) administered by mouth approximately thirty to sixty minutes prior to each study drug infusion. Dose may be repeated every four hours, as needed.

DRUG

acetaminophen

Acetaminophen 650 mg (or equivalent) administered by mouth approximately thirty to sixty minutes prior to each study drug infusion. Dose may be repeated every four hours, as needed.

Sponsors & Collaborators

• Autoimmunity Centers of Excellence

  collaborator OTHER

• Rho Federal Systems Division, Inc.

  collaborator INDUSTRY

• National Institute of Allergy and Infectious Diseases (NIAID)

  lead NIH

Principal Investigators

• Mark Nicolls, M.D. · Stanford University

• David B. Badesch, M.D. · University of Colorado Health Sciences Center (Aurora, CO)

• Thomas A. Medsger, Jr., M.D. · University of Pittsburgh

• Lorinda Chung, MD · Stanford University

• Robyn Domsic, MD · University of Pittsburgh: Division of Rheumatology and Clinical Immunology

• Aryeh Fischer, MD · National Jewish Health: University of Colorado School of Medicine

• Roham Zamanian, MD · Stanford University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2011-06-24

Primary Completion

2018-06-05

Completion

2019-12-15

Countries

• United States

Study Locations