Clinical trial NCT01559129: Study of Pomalidomide (CC-4047) to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effectiveness for Patients With Systemic Sclerosis With Interstitial Lung Disease
Official 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Scleroderma, Systemic
Sclerosis, Systemic
Systemic Scleroderma
Systemic Sclerosis
Interstitial Lung Disease
Lead sponsor: Celgene
Sponsor class: INDUSTRY
First posted: 2012-03-21
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: 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.
measure: Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52
timeFrame: Baseline (defined as the average of all values between Screening and Baseline) and Weeks 48 and 52
measure: Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52/Early Termination
timeFrame: Baseline and Week 52 (or the Treatment Phase Early Termination visit)
measure: 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
timeFrame: Baseline and Week 52 (or Treatment Phase Early Termination visit)
Secondary outcomes:
measure: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time
timeFrame: Baseline (defined as the average of all values between Screening and Baseline) and Weeks 12, 24, 36, 64, 76, and 156
measure: Change From Baseline in Modified Rodnan Skin Score Over Time
timeFrame: Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).
measure: Change From Baseline in UCLA SCTC GIT 2.0 Total Score Over Time
timeFrame: Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).
measure: Change From Baseline in UCLA SCTC GIT 2.0 Reflux Subscale Score Over Time
timeFrame: 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).
measure: Change From Baseline in UCLA SCTC GIT 2.0 Distension/Bloating Subscale Score Over Time
timeFrame: 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).
measure: Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time
timeFrame: 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).
measure: Change From Baseline in UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time
timeFrame: 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).
measure: Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time
timeFrame: 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).
measure: Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time
timeFrame: 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).
measure: Change From Baseline in UCLA SCTC GIT 2.0 Constipation Subscale Score Over Time
timeFrame: 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).
measure: Change From Baseline in Dyspnea Functional Impairment at Week 12
timeFrame: Week 12
measure: Change From Baseline in Dyspnea Functional Impairment at Week 24
timeFrame: Week 24
measure: Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination
timeFrame: Week 52 or at the Treatment Phase Early Termination visit
measure: Change From Baseline in Dyspnea Functional Impairment at Week 64
timeFrame: Week 64
measure: Change From Baseline in Dyspnea Functional Impairment at Week 76
timeFrame: Week 76
measure: Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination
timeFrame: Week 156 or the Extension Phase Early Termination visit
measure: Change From Baseline in Dyspnea Magnitude of Task at Week 12
timeFrame: Week 12
measure: Change From Baseline in Dyspnea Magnitude of Task at Week 24
timeFrame: Week 24
measure: Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination
timeFrame: Week 52 or at the Treatment Phase Early Termination visit
measure: Change From Baseline in Dyspnea Magnitude of Task at Week 64
timeFrame: Week 64
measure: Change From Baseline in Dyspnea Magnitude of Task at Week 76
timeFrame: Week 76
measure: Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination
timeFrame: Week 156 or the Extension Phase Early Termination visit
measure: Change From Baseline in Dyspnea Magnitude of Effort at Week 12
timeFrame: Week 12
measure: Change From Baseline in Dyspnea Magnitude of Effort at Week 24
timeFrame: Week 24
measure: Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination
timeFrame: Week 52 or at the Treatment Phase Early Termination visit
measure: Change From Baseline in Dyspnea Magnitude of Effort at Week 64
timeFrame: Week 64
measure: Change From Baseline in Dyspnea Magnitude of Effort at Week 76
timeFrame: Week 76
measure: Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination
timeFrame: Week 156 or at the Extension Phase Early Termination visit
measure: Oxygen Saturation Over Time
timeFrame: 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).
measure: Pharmacokinetic Parameters of Pomalidomide in Plasma
timeFrame: Day 1 and week 4 pre-dose and up to 24 hours post-dose.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA Division of Rheumatology
state: California
city: Rancho Mirage
country: United States
facility: Advances in Medicine
state: California
city: Newark
country: United States
facility: Delaware Medical Care Associates, LLC
state: Delaware
city: Washington
country: United States
facility: Georgetown University School of Medicine
state: District of Columbia
city: Tampa
country: United States
facility: USF Health Faculty Office Building-FOB
state: Florida
city: Stockbridge
country: United States
facility: Arthritis Research and Treatment Center
state: Georgia
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Michigan City
country: United States
facility: LaPorte County Institute for Clinical Research, Inc
state: Indiana
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Shreveport
country: United States
facility: Louisiana State University
state: Louisiana
city: Boston
country: United States
facility: Boston University of Medicine BUMC
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: New Brunswick
country: United States
facility: UMDNJ-Robert Wood Johnson Medical School Clinical Research Center
state: New Jersey
city: Great Neck
country: United States
facility: North Shore-LIJ Health System-Division of Rheumatology
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Toledo
country: United States
facility: University of Toledo College of Medicine
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: University of Texas Health Science Center at Houston
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Chermside
country: Australia
facility: The Prince Charles Hospital
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
city: Lille
country: France
facility: CHRU de Lille FR
city: Paris
country: France
facility: Hopital Saint Louis
city: Paris
country: France
facility: Groupe Hospitalier Saint Vincent de Paul
city: Bad Nauheim
country: Germany
facility: Kerckhoff-Klinik gGmbH
city: Berlin
country: Germany
facility: Charite - Universitätsmedizin Berlin
city: Erlangen
country: Germany
facility: University of Erlangen-Nuremberg
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Gothe-Universitat Frankfurt
city: Herne
country: Germany
facility: Rheumazentrum Ruhrgebiet
city: Ulm
country: Germany
facility: University Hospital of Ulm
city: Genova
country: Italy
facility: Azienda Ospedaliera Universitaria S. Martino di Genova
city: Milano
country: Italy
facility: Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
city: Pavia
country: Italy
facility: IRCCS Policlinico S. Matteo di Pavia
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
city: Roma
country: Italy
facility: Policlinico Umberto I
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
city: Bialystok
country: Poland
facility: Centrum Miriada Prywatny Gabinet Specjalistyczny Profesora Dra Stanislawa Sierakowskiego
city: Bydgoszcz
country: Poland
facility: Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
city: Katowice
country: Poland
facility: SPSK Nr 7 Slaskiego Uniwersytetu Medycznego, Oddzial Chorob Wewnetrznych i Reumatologii
city: Szczecin
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego Pomorskiego UM w Szczec
city: Warszawa
country: Poland
facility: Instytut Reumatologii, Klinika i Poliklinika Ukladowych Chorób Tkanki Lacznej
city: Wroclaw
country: Poland
facility: Akademicki Szpital Kliniczny Klinika Reumatologii i Chorob Wewnetrznych
city: Moscow
country: Russian Federation
facility: Institution of the Russian Academy of Medical Sciences Research Institute of Rheumatology of the Ru
city: Penza
country: Russian Federation
facility: Penza Regional Clinical Hospital n.a. N.N. Burdenko
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg State Healthcare Institution "Clinical Rheumatology Hospital # 25"
city: Madrid
country: Spain
facility: Hospital Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario de Santiago
city: Valencia
country: Spain
facility: Hospital Universitario Dr. Peset
city: Basel
country: Switzerland
facility: University Hospital Basel
city: Leeds
country: United Kingdom
facility: Chapel Allerton Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Royal Brompton Hospital - Interstitial Lung Disease Unit
Study officials:
affiliation: Celgene Corporation
name: Shimon Korish, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.