Study of Pomalidomide (CC-4047) to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effectiveness for Patients With Systemic Sclerosis With Interstitial Lung Disease

A Phase 2, Proof-Of-Concept, Multicenter, Randomized, Double-Blind, Placebo- Controlled, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Pomalidomide (CC-4047) in Subjects With Systemic Sclerosis With Interstitial Lung Disease

The primary objective of this study is to evaluate the safety, tolerability, and efficacy of pomalidomide in the treatment of patients with systemic sclerosis with interstitial lung disease.

Inclusion Criteria

• Male or females between 18 and 80 years of age (inclusive) at the time of consent.

• Diagnosis of systemic sclerosis (SSC) as defined by American College of Rheumatology (ACR) criteria.

• Onset of the first non-Raynaud's manifestation of SSC within 7 years of Screening.

• Subjects are required to meet at least one of the following 2 pulmonary-related criteria to be eligible for the study:.

  i) FVC readings ≥ 70% and ≤ 80% at Screening and Baseline (Visit 2) with a documented history of either or both of:.

A. A ≥ 5% decrease (expressed as percent predicted or in liters) in FVC in the 24-month period prior to Baseline (Visit 2) based on 3 or more assessments. Two assessments may be done during the Screening phase provided the assessments are completed at least 2 weeks apart.

B. A high resolution computed tomography (HRCT) fibrosis score > 20%.

ii) Forced vital capacity (FVC) ≥ 45% and <70% at Screening and Baseline (Visit 2) [with or without a documented pre-specified FVC decline or fibrosis score].

• FVC at Baseline (Visit 2) within 5% of the FVC measured at Screening.
• Carbon monoxide diffusing capacity (DLco) ≥ 35% and ≤ 80% of predicted value at Screening.
• Abnormalities on High-Resolution CT consistent with parenchymal changes encountered in SSc: honeycombing or reticular changes with or without ground glass.

Exclusion Criteria

• Oxygen saturation (SpO2) < 92% (room air [sea level] at rest) at Screening or Baseline.
• Known diagnosis of obstructive lung disease as defined by forced expiratory volume (FEV1)/FVC ratio < 0.7.
• Diagnosis of pulmonary arterial hypertension (PAH) requiring treatment.
• Known diagnosis of other significant respiratory disorders (e.g., asthma, tuberculosis, sarcoidosis, aspergillosis, chronic bronchitis, neoplastic disease, cystic fibrosis, etc.).
• Current clinical diagnosis of another inflammatory connective tissue disease (eg, systemic lupus erythematosus, rheumatoid arthritis, primary Sjogren's syndrome, etc.). Subjects having Sjogren's syndrome secondary to SSc are eligible.
• Pregnant or lactating females.
• History of a thromboembolic event (eg, deep vein thrombosis, thrombotic cerebrovascular or cardiovascular events).
• History or current diagnosis of peripheral neuropathy.
• Use of concomitant medication(s) which could increase the risk for developing deep vein thrombosis, including sex steroid-based contraceptives (oral, injectable or implanted) and hormone replacement therapies, if use of a low-dose aspirin regimen is contraindicated.
• Additional concomitant medications which prolong the QT/QTc interval (measure of heart's electrical cycle) during the course of the study.
• Use of any anti-coagulant or anti-thrombotic medications (other than low dose-aspirin [≤ 100 mg/day]).
• Use of any cytotoxic/immunosuppressive agent (other than prednisone ≤ 10 mg/day [mean dose] or equivalent), including but not limited to azathioprine, cyclophosphamide, methotrexate, mycophenolate and cyclosporine within 28 days (4 weeks) of Screening.
• Use of any biologic agent within 84 days (12 weeks) or 5 half-lives of Screening. In the case of rituximab, use within 168 days (24 weeks) of Screening or no recovery of CD20-positive B lymphocytes if the last dose of rituximab has been more than 24 weeks prior to Screening.
• Use of bosentan, ambrisentan, sildenafil, tadalafil and macitentan for PAH within 28 days (4 weeks) of Screening.
• Use of medications (e.g., D-penicillamine, Potaba) with putative scleroderma disease-modifying properties within 4 weeks of Screening.
• Use of melphalan within 52 weeks of Screening.
• Use of any investigational drug within 4 weeks of Screening or 5 pharmacodynamic/pharmacokinetic half-lives if known (whichever is longer).
• Smoking of cigars, pipes or cigarettes within 24 weeks of Screening.
• Other protocol-defined Inclusion/Exclusion criteria apply.