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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT01559129




Registration number
NCT01559129
Ethics application status
Date submitted
19/03/2012
Date registered
21/03/2012
Date last updated
1/12/2023

Titles & IDs
Public title
Study of Pomalidomide (CC-4047) to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effectiveness for Patients With Systemic Sclerosis With Interstitial Lung Disease
Scientific title
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
Secondary ID [1] 0 0
2010-023047-15
Secondary ID [2] 0 0
CC-4047-SSC-001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Scleroderma, Systemic 0 0
Sclerosis, Systemic 0 0
Systemic Scleroderma 0 0
Systemic Sclerosis 0 0
Interstitial Lung Disease 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 0 0 0 0
Autoimmune diseases
Skin 0 0 0 0
Dermatological conditions
Skin 0 0 0 0
Other skin conditions

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Pomalidomide (CC-4047)
Treatment: Drugs - Placebo

Placebo Comparator: Placebo -

Experimental: Pomalidomide - Participants received 1 mg pomalidomide orally once a day for 52 weeks during the treatment phase and for up to 2 years during the open-label extension phase.


Treatment: Drugs: Pomalidomide (CC-4047)
1 mg orally every day for 52 weeks

Treatment: Drugs: Placebo
Matching placebo capsules taken orally once a day
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
From the start of study drug to 28 days after last dose; Treatment Phase median duration of treatment was 358 and 320 days for Placebo and Pomalidomide; Extension phase median duration of treatment was 161 days and 194 days for Placebo and pomalidomide.
Primary outcome [2] 0 0
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52
Timepoint [2] 0 0
Baseline (defined as the average of all values between Screening and Baseline) and Weeks 48 and 52
Primary outcome [3] 0 0
Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52/Early Termination
Timepoint [3] 0 0
Baseline and Week 52 (or the Treatment Phase Early Termination visit)
Primary outcome [4] 0 0
Change From Baseline in University of California, Los Angeles, Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) Total Score at Week 52/Early Termination
Timepoint [4] 0 0
Baseline and Week 52 (or Treatment Phase Early Termination visit)
Secondary outcome [1] 0 0
Change From Baseline in Percent Predicted Forced Vital Capacity Over Time
Timepoint [1] 0 0
Baseline (defined as the average of all values between Screening and Baseline) and Weeks 12, 24, 36, 64, 76, and 156
Secondary outcome [2] 0 0
Change From Baseline in Modified Rodnan Skin Score Over Time
Timepoint [2] 0 0
Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [3] 0 0
Change From Baseline in UCLA SCTC GIT 2.0 Total Score Over Time
Timepoint [3] 0 0
Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [4] 0 0
Change From Baseline in UCLA SCTC GIT 2.0 Reflux Subscale Score Over Time
Timepoint [4] 0 0
Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [5] 0 0
Change From Baseline in UCLA SCTC GIT 2.0 Distension/Bloating Subscale Score Over Time
Timepoint [5] 0 0
Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [6] 0 0
Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time
Timepoint [6] 0 0
Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [7] 0 0
Change From Baseline in UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time
Timepoint [7] 0 0
Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [8] 0 0
Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time
Timepoint [8] 0 0
Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [9] 0 0
Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time
Timepoint [9] 0 0
Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [10] 0 0
Change From Baseline in UCLA SCTC GIT 2.0 Constipation Subscale Score Over Time
Timepoint [10] 0 0
Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [11] 0 0
Change From Baseline in Dyspnea Functional Impairment at Week 12
Timepoint [11] 0 0
Week 12
Secondary outcome [12] 0 0
Change From Baseline in Dyspnea Functional Impairment at Week 24
Timepoint [12] 0 0
Week 24
Secondary outcome [13] 0 0
Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination
Timepoint [13] 0 0
Week 52 or at the Treatment Phase Early Termination visit
Secondary outcome [14] 0 0
Change From Baseline in Dyspnea Functional Impairment at Week 64
Timepoint [14] 0 0
Week 64
Secondary outcome [15] 0 0
Change From Baseline in Dyspnea Functional Impairment at Week 76
Timepoint [15] 0 0
Week 76
Secondary outcome [16] 0 0
Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination
Timepoint [16] 0 0
Week 156 or the Extension Phase Early Termination visit
Secondary outcome [17] 0 0
Change From Baseline in Dyspnea Magnitude of Task at Week 12
Timepoint [17] 0 0
Week 12
Secondary outcome [18] 0 0
Change From Baseline in Dyspnea Magnitude of Task at Week 24
Timepoint [18] 0 0
Week 24
Secondary outcome [19] 0 0
Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination
Timepoint [19] 0 0
Week 52 or at the Treatment Phase Early Termination visit
Secondary outcome [20] 0 0
Change From Baseline in Dyspnea Magnitude of Task at Week 64
Timepoint [20] 0 0
Week 64
Secondary outcome [21] 0 0
Change From Baseline in Dyspnea Magnitude of Task at Week 76
Timepoint [21] 0 0
Week 76
Secondary outcome [22] 0 0
Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination
Timepoint [22] 0 0
Week 156 or the Extension Phase Early Termination visit
Secondary outcome [23] 0 0
Change From Baseline in Dyspnea Magnitude of Effort at Week 12
Timepoint [23] 0 0
Week 12
Secondary outcome [24] 0 0
Change From Baseline in Dyspnea Magnitude of Effort at Week 24
Timepoint [24] 0 0
Week 24
Secondary outcome [25] 0 0
Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination
Timepoint [25] 0 0
Week 52 or at the Treatment Phase Early Termination visit
Secondary outcome [26] 0 0
Change From Baseline in Dyspnea Magnitude of Effort at Week 64
Timepoint [26] 0 0
Week 64
Secondary outcome [27] 0 0
Change From Baseline in Dyspnea Magnitude of Effort at Week 76
Timepoint [27] 0 0
Week 76
Secondary outcome [28] 0 0
Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination
Timepoint [28] 0 0
Week 156 or at the Extension Phase Early Termination visit
Secondary outcome [29] 0 0
Oxygen Saturation Over Time
Timepoint [29] 0 0
Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).
Secondary outcome [30] 0 0
Pharmacokinetic Parameters of Pomalidomide in Plasma
Timepoint [30] 0 0
Day 1 and week 4 pre-dose and up to 24 hours post-dose.

Eligibility
Key inclusion 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.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/08/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
3/11/2016
Sample size
Target
Accrual to date
Final
23
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Monash Medical Centre - Clayton
Recruitment hospital [2] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
4032 - Chermside
Recruitment postcode(s) [3] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Delaware
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Kentucky
Country [9] 0 0
United States of America
State/province [9] 0 0
Louisiana
Country [10] 0 0
United States of America
State/province [10] 0 0
Massachusetts
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
United States of America
State/province [17] 0 0
Wisconsin
Country [18] 0 0
France
State/province [18] 0 0
Lille
Country [19] 0 0
France
State/province [19] 0 0
Paris
Country [20] 0 0
Germany
State/province [20] 0 0
Bad Nauheim
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Germany
State/province [22] 0 0
Erlangen
Country [23] 0 0
Germany
State/province [23] 0 0
Frankfurt
Country [24] 0 0
Germany
State/province [24] 0 0
Herne
Country [25] 0 0
Germany
State/province [25] 0 0
Ulm
Country [26] 0 0
Italy
State/province [26] 0 0
Genova
Country [27] 0 0
Italy
State/province [27] 0 0
Milano
Country [28] 0 0
Italy
State/province [28] 0 0
Pavia
Country [29] 0 0
Italy
State/province [29] 0 0
Pisa
Country [30] 0 0
Italy
State/province [30] 0 0
Roma
Country [31] 0 0
Poland
State/province [31] 0 0
Bialystok
Country [32] 0 0
Poland
State/province [32] 0 0
Bydgoszcz
Country [33] 0 0
Poland
State/province [33] 0 0
Katowice
Country [34] 0 0
Poland
State/province [34] 0 0
Szczecin
Country [35] 0 0
Poland
State/province [35] 0 0
Warszawa
Country [36] 0 0
Poland
State/province [36] 0 0
Wroclaw
Country [37] 0 0
Russian Federation
State/province [37] 0 0
Moscow
Country [38] 0 0
Russian Federation
State/province [38] 0 0
Penza
Country [39] 0 0
Russian Federation
State/province [39] 0 0
St. Petersburg
Country [40] 0 0
Spain
State/province [40] 0 0
Madrid
Country [41] 0 0
Spain
State/province [41] 0 0
Santiago de Compostela
Country [42] 0 0
Spain
State/province [42] 0 0
Valencia
Country [43] 0 0
Switzerland
State/province [43] 0 0
Basel
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Leeds
Country [45] 0 0
United Kingdom
State/province [45] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Celgene
Address
Country

Ethics approval
Ethics application status

Summary
Brief 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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT01559129
Trial related presentations / publications
Hsu VM, Denton CP, Domsic RT, Furst DE, Rischmueller M, Stanislav M, Steen VD, Distler JHW, Korish S, Cooper A, Choi S, Schafer PH, Horan G, Hough DR. Pomalidomide in Patients with Interstitial Lung Disease due to Systemic Sclerosis: A Phase II, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study. J Rheumatol. 2018 Mar;45(3):405-410. doi: 10.3899/jrheum.161040. Epub 2017 Nov 1.
Hsu V, et al. A Phase 2 Study of Pomalidomide (CC-4047) to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effectiveness in Subjects with Systemic Sclerosis with Interstitial Lung Disease. Presented at the 2016 ACR/ARHP Annual Meeting, November 11-16, 2016, Washington, DC. Abstract No. 823.
Public notes

Contacts
Principal investigator
Name 0 0
Shimon Korish, MD
Address 0 0
Celgene Corporation
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT01559129