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

Completed · Phase 2 · Has a placebo group

Conditions studied: Systemic Sclerosis-Associated PAH

In brief

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 facts

Study ID

NCT01086540

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

57

Starts

2011-06-24

Expected to finish

2019-12-15

Last updated by the study team

2023-02-21

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Subject has provided written informed consent.
• 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.

You may not qualify if…

• Documented PAH for greater than 5 years at the time of randomization defined as:
• Measurement of a mean Pulmonary Artery Pressure (PAP) > 25 mmHg by right heart catheterization at least 5 years previously, OR
• Treatment with targeted background PAH therapy for > 5 years.
• Pulmonary Capillary Wedge Pressure > 15 mmHg or Left Ventricular End Diastolic Pressure > 15 mmHg.
• Persistent hypotension with Systolic Blood Pressure (SBP) < 90 mmHg.
• Treatment with cyclophosphamide within 4 weeks of randomization.
• Treatment with immunocompromising biologic agents within 4 weeks prior to treatment initiation or treatment with infliximab within 8 weeks prior to treatment initiation.
• If being treated with a non-biologic immunosuppressive or immunomodulating drug, changes in dosage within 4 weeks prior to randomization. Subjects taking prednisone or equivalent corticosteroid > 10mg daily are excluded.
• Previous exposure to any lymphocyte or B cell depleting agent.
• PAH for any reason other than SSc.
• History of coronary artery disease, significant ventricular tachy-arrhythmia, stent placement, coronary artery bypass surgery, and/or myocardial infarction.
• Moderate or severe interstitial lung disease.
• Chronic infections.
• Positive serology for infection with hepatitis B or C.
• A deep space infection within the past 2 years.
• Evidence of active infection within 2 weeks of randomization
• Presence of a positive tuberculosis (TB) skin test (e.g., PPD test) or positive QuantiFERON®-TB blood test, an indeterminate QuantiFERON®-TB blood test, or latent tuberculosis (TB).
• Significant renal insufficiency.
• Active, untreated SSc renal crisis at the time of enrollment.
• Recent administration of a live vaccine (< 8 weeks) or any other immunization within 4 weeks of treatment.
• History of anaphylaxis or Immunoglobulin E (IgE) -mediated hypersensitivity to murine proteins or any component of rituximab.
• Pregnancy.
• Lactation.
• History of malignancy within the last 5 years, except for resected basal or squamous cell carcinoma, treated cervical dysplasia, or treated in situ cervical cancer Grade I.
• A woman of childbearing potential who is unwilling to use a medically acceptable form of birth control

Where it is running

• Stanford Health Care — Stanford, California, United States
• University of Colorado Health Sciences Center — Aurora, Colorado, United States
• University of Iowa — Iowa City, Iowa, United States
• Johns Hopkins University, Pulmonary and Critical Care Medicine — Baltimore, Maryland, United States
• Boston University Medical Center — Boston, Massachusetts, United States
• University of Michigan — Ann Arbor, Michigan, United States
• University of Minnesota Health Clinics and Surgery Center — Minneapolis, Minnesota, United States
• Columbia University Medical Center — New York, New York, United States
• Weill Cornell Medical College — New York, New York, United States
• University of Rochester Medical Center — Rochester, New York, United States
• University of North Carolina at Chapel Hill: UNC Hospitals — Chapel Hill, North Carolina, United States
• Ohio State University — Columbus, Ohio, United States
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• University of Texas Southwestern Medical Center-William P. Clements University Hospital — Dallas, Texas, United States
• University of Texas: Memorial Herman Hospital — Houston, Texas, United States
• University of Utah — Salt Lake City, Utah, United States

Full record on ClinicalTrials.gov

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