Overview

This trial is active, not recruiting.

Conditions scleroderma, systemic, sclerosis, systemic, systemic scleroderma, systemic sclerosis
Treatments pomalidomide (cc-4047), placebo
Phase phase 2
Sponsor Celgene Corporation
Start date August 2012
End date February 2019
Trial size 23 participants
Trial identifier NCT01559129, 2010-023047-15, CC-4047-SSC-001

Summary

The purpose of this first study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of pomalidomide (CC-4047) in the treatment of subjects with systemic sclerosis with interstitial lung disease.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator)
Primary purpose treatment
Arm
(Active Comparator)
pomalidomide (cc-4047)
1 mg orally every day for 52 weeks
(Placebo Comparator)
placebo
Placebo

Primary Outcomes

Measure
Type, frequency, severity and relationship of Adverse Events (AE) and Serious Adverse Events to pomalidomide
time frame: Up to 156 weeks
Change from Baseline (Week 0) of the forced vital capacity (FVC) at Week 52 in Systemic Sclerosis subjects
time frame: Baseline and Week 52
Change from Baseline (Week 0) of the modified Rodnan Skin Score (mRSS) at Week 52
time frame: Baseline and Week 52
Change from Baseline of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) total score in Systemic Sclerosis subjects
time frame: Baseline and Week 52

Secondary Outcomes

Measure
Area Under the Time Curve (AUCt)
time frame: Up to 8 weeks
Pharmacokinetic Parameter -Cmax
time frame: Up to 8 weeks
Pharmacokinetic Parameter - Tmax
time frame: Up to 8 weeks
Change from Baseline (Week 0) of the FVC at Week 12
time frame: Baseline and Week 12
Change from Baseline (Week 0) of the Modified Rodnan Skin Score at Week 12
time frame: Baseline and Week 12
Change from Baseline (Week 0) of the UCLA SCTC GIT 2.0 total score at Week 12
time frame: Baseline and Week 12
Change from Baseline (Week 0) UCLA SCTC GIT 2.0 subscale scores (Reflux, Distention/Bloating, Fecal Soilage, Diarrhea, Social functioning, Emotional Well-being and Constipation) at Week 12
time frame: Baseline and Week 12
Change from Baseline (Week 0) of the oxygen saturation (as measured by pulse oximetry) at Week 12
time frame: Baseline and Week 12
Change from Baseline (Week 0) dyspnea (as measured by the Transition Dyspnea Index) at Week 12
time frame: Baseline and Week 12
Change from Baseline (Week 0) of the forced vital capacity (FVC) at Week 24
time frame: Baseline and Week 24
Change from Baseline (Week 0) and Week 24 of the modified Rodnan Skin Score (mRSS) at Week 24
time frame: Baseline and Week 24
Change from Baseline in the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) total score at Week 24
time frame: Baseline and Week 24
Change from Baseline in the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) subscore (Reflux, Distention, Bloating, Fecal Silage, Social functioning, Emotional Well-being and Constipation s at Week 24
time frame: Baseline and Week 24
Change from Baseline in the oxygen saturation (as measured by pulse oximetry) in Systemic Sclerosis subjects at Week 24
time frame: Baseline and Week 24
Change from Baseline (Week 0) in dyspnea (as measured by the Transition Dyspnea Index (TDI) at Week 24
time frame: Baseline and Week 24
Change from Baseline (Week 0) of the forced vital capacity (FVC) at Week 36
time frame: Baseline and Week 36
Change from Baseline (Week 0) of the forced vital capacity (FVC) at Week 48
time frame: Baseline and Week 48
Change from Baseline in the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) subscore (Reflux, Distention, Bloating, Fecal Silage, Social functioning, Emotional Well-being and Constipation s at Week 52
time frame: Baseline and Week 52
Change from Baseline in the oxygen saturation (as measured by pulse oximetry) at Week 52
time frame: Baseline and Week 52
Change from Baseline (Week 0) in dyspnea (as measured by the Transition Dyspnea Index (TDI) at Week 52
time frame: Baseline and Week 52
Change from Baseline (Week 0) and Week 52 of the forced vital capacity (FVC) at Weeks 64, 76, 88, 100, 104, 128, 156
time frame: Baseline to week s 64, 76, 88, 100, 104, 128 and 156
Change from Baseline (Week 0) and Week 52 of the modified Rodnan Skin Score (mRSS) at Weeks 64, 76, 104, 128, 156
time frame: Baseline to Weeks 64, 76, 104, 128 and 156
Change from Baseline and Week 52 in the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) total score at Weeks 64, 76, 104, 128 and 156
time frame: Baseline to Weeks 64, 76, 104, 128 and 156
Change from Baseline and Week 52 in the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) subscore (Reflux, Distention, Bloating, Fecal Silage, Social functioning, Emotional Well-being and Constipation)
time frame: Baseline to Weeks 64, 76, 104, 128 and 156
Change from Baseline and Week 52 in the oxygen saturation (as measured by pulse oximetry) at Weeks 64, 76, 104, 128 and 156
time frame: Baseline to weeks 64, 76, 88, 100, 104, 128 and 156
Change from Baseline (Week 0 and Week 52) in dyspnea (as measured by the Transition Dyspnea Index (TDI) at Weeks 64, 76, 104, 128 and 156
time frame: Baseline to weeks 64, 76, 88, 100, 104, 128 and 156

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria: - Male or females between 18 and 80 years of age (inclusive) at the time of consent - Diagnosis of SSC as defined by 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: - Repeat 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 computed tomography consistent with sclerodermatous involvement of the lung (eg, ground glass, honeycombing) FVC ≥ 45% and <70% at Screening and Baseline (Visit 2) [with or without a documented pre-specified FVC decline or fibrosis score] OR FVC readings ≥ 70% and ≤ 80% at Screening and Baseline (Visit 2) with a documented history of either or both of: 1. 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. 2. An HRCT fibrosis score > 20% 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 (e.g., systemic lupus erythematosus, rheumatoid arthritis, Sjogren's syndrome, etc.) - Use of melphalan within 52 weeks of Screening - 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 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

Additional Information

Official title A Phase 2, Proof-Of-Concept, Multicenter, Randomized, Double-Blind, Placebo- Controlled, Study to Evaluate the Safety, Tolerablity, Pharmacokinetics, Pharmacodynamics and Efficacy of Pomalidomide (CC-4047) in Subjects With Systemic Sclerosis With Interstitial Lung Disease
Description Based upon interim analysis data from the Phase 2 proof of concept study in subjects with systemic sclerosis with interstitial lung disease (CC-4047-SSC-001), the study did not meet its primary endpoint of improvement in Forced Vital Capacity (FVC) nor for improvement in the modified Rodnan skin score at 24 and 52 weeks, for subjects who had completed blinded treatment. In this study, pomalidomide was well tolerated with an adverse event profile comparable to the risk safety information known for pomalidomide in other diseases. Treatment has stopped, but patients will remain in follow up.
Trial information was received from ClinicalTrials.gov and was last updated in November 2016.
Information provided to ClinicalTrials.gov by Celgene Corporation.