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

Conditions

• Systemic Sclerosis-Associated PAH

Eligibility Criteria

Sex

ALL

Age

18 Years - 75 Years

Healthy Volunteers

Not accepted

Interventions

• Rituximab — BIOLOGICAL
  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.
• Placebo — OTHER
  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.
• CMRI — DIAGNOSTIC_TEST
  Up to 20 participants from each treatment arm will be assessed by CMRI at Baseline and at Week 24.
• prednisone — DRUG
  Prednisone dose of 40 mg (or equivalent) by mouth administered the night before and the morning of each study drug infusion.
• methylprednisolone — DRUG
  Methylprednisolone (or equivalent corticosteroid) administered intravenously 30 minutes prior to each study drug infusion.
• diphenhydramine — DRUG
  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.
• acetaminophen — DRUG
  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.

Study Details

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.

Key Dates

Start date

Jun 24, 2011

Status verified

Jan 2023

Primary completion

Jun 5, 2018

Completion

Dec 15, 2019

Study Design

Enrollment

57 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Rituximab+PAH SOC
  Rituximab (1000 mg) will be administered as 2 intravenous infusions given 2 weeks apart. Concurrent stable-dose Pulmonary Arterial Hypertension (PAH) medical therapy will be continued/managed as per standard of care (PAH SOC).
• Placebo Comparator: Placebo + PAH SOC
  Placebo will be administered as 2 intravenous infusions given 2 weeks apart. Concurrent stable-dose Pulmonary Arterial Hypertension (PAH) medical therapy will be continued/managed as per standard of care (PAH SOC).

Primary Outcome Measure

Change From Baseline in Distance Walked During a Six Minute Walk Test [ Time Frame: Baseline (Pre Treatment Initiation) to Week 24 ]

Locations (17)

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