Study of Pomalidomide (CC-4047) to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effectiveness for Patients With Systemic Sclerosis With Interstitial Lung Disease
Condition: Scleroderma, Systemic; Sclerosis, Systemic; Systemic Scleroderma; Systemic Sclerosis; Interstitial Lung Disease
MeSH terms: Lung Diseases; Lung Diseases, Interstitial; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized; Sclerosis
Intervention: Pomalidomide (CC-4047); Placebo
Intervention description: 1 mg orally every day for 52 weeks; Matching placebo capsules taken orally once a day
Intervention MeSH terms: Pomalidomide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        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.