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

Exclusion Criteria

• •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
• •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 g/dL.
• •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.