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Trial ID: NCT01086540,23502
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)
Stanford University Professor of Pulmonary and Critical Care Medicine
Professor of Medicine (Immunology and Rheumatology) and, by courtesy, of Dermatology
Professor of Medicine (Pulmonary and Critical Care Medicine)
- Subject has provided written informed consent.
- Clinical diagnosis of systemic sclerosis (either limited or diffuse cutaneous
- 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
- 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
- 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.
- 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
- A woman of childbearing potential who is unwilling to use a medically acceptable form
of birth control
- History of non-compliance with other medical therapies.
- History of alcohol or drug abuse within 1 year of randomization.
- Receipt of any investigational drug or device within 4 weeks before the Screening
Visit, with the exception of investigational prostanoids, endothelin receptor
antagonists, and PDE-5 inhibitors, and guanylate cyclase stimulators.
- Recipient of lung transplant.
- Laboratory parameters at the screening visit showing any of the following abnormal
results: Transaminases > 2x the upper limit of normal (ULN) and/or bilirubin > 2x ULN;
Absolute neutrophil count < 1,500/mm^3; Platelet count < 100,000/mm^3; Hemoglobin < 9
- Concurrent treatment in a clinical research study using a non-FDA approved agent with
the exception of an open-label study/study extension of investigational prostanoids,
endothelin receptor antagonists, and PDE-5 inhibitors, and guanylate cyclase
stimulators, provided the open-label investigational drug will be available and dose
will remain stable through the trial's primary outcome time point of 24 weeks after
randomization in this study, ASC01 (NCT01086540).
- Any condition or treatment, which in the opinion of the investigator, places the
subject at unacceptable risk as a participant in the trial.
diagnostic test: CMRI
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