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

NCT01559129 | Terminated Phase 2 Results DMC

• 2 other identifiers: CC-4047-SSC-0012010-023047-15
• Study Type: interventional
• Target: 23
• Locations: 10 countries
• Sites: 56

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.

Conditions

Scleroderma, Systemic; Sclerosis, Systemic; Systemic Scleroderma; Systemic Sclerosis; Interstitial Lung Disease

Outcome Measures

Primary Outcomes (4)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  An adverse event (AE) is any noxious, unintended, or untoward medical occurrence that may appear or worsen during the course of a study. A TEAE is any AE that began or worsened on or after the start of study drug through 28 days after the last dose. A treatment-related TEAE is a TEAE which was considered by the investigator to be related to study drug. The severity/intensity of AEs was assessed by the investigator as Mild (asymptomatic or mild symptoms; intervention not indicated), Moderate (symptoms cause moderate discomfort, intervention may be required), or Severe (symptoms cause severe discomfort/pain, requiring medical intervention, inability to perform daily activities). A serious AE is any AE that: - Resulted in death; - Was life-threatening; - Required inpatient hospitalization or prolongation of existing hospitalization - Resulted in persistent or significant disability/incapacity; - Was a congenital anomaly/birth defect; - Constituted an important medical event.

  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.

• Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52

  Forced vital capacity (FVC) is a pulmonary function test and is the volume of air in the lungs that can forcibly be blown out after a full inhalation. Percent predicted values are based comparison between the participant's measured value with expected FVC for someone of the same sex, age and height (reference value). For the analysis of FVC, the baseline value was defined as the average of all values between Screening and Baseline (inclusive), and the average of Weeks 48 and 52 was treated as the Week 52 value, to reduce the total data variability at the key time points.

  Baseline (defined as the average of all values between Screening and Baseline) and Weeks 48 and 52

• Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52/Early Termination

  Improvement in skin thickening is associated with improved survival and may be useful as a surrogate measurement in clinical studies. The mRSS is an assessment tool which is used to evaluate the extent and severity of the skin thickening associated with systemic sclerosis (SSc). Seventeen body areas were evaluated on a 4-point scale (0 \[normal\], 1 \[mild\], 2 \[moderate\]), or 3 \[severe\]). The total score, which is the sum of the 17 individual body assessments, can range from 0 to 51.

  Baseline and Week 52 (or the Treatment Phase Early Termination visit)

• 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

  The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets gastrointestinal (GI) activity and severity in patients with SSc. Individual scales include reflux, distention/bloating, fecal soilage, diarrhea, social functioning, emotional well-being and constipation. The items are scored on a scale from 0 to 3, where 0 indicates better health and 3 indicates worse health (except for Questions 15 and 31 which are scored as 0 (better health) or 1 (worse health). The total score is calculated as the average of the first 6 scale scores (excluding constipation) which captures overall burden (severity) of SSc-associated GIT. The overall score ranges from 0 to 3, where higher scores indicate more severe symptoms.

  Baseline and Week 52 (or Treatment Phase Early Termination visit)

Secondary Outcomes (30)

• Change From Baseline in Percent Predicted Forced Vital Capacity Over Time

  Baseline (defined as the average of all values between Screening and Baseline) and Weeks 12, 24, 36, 64, 76, and 156

• Change From Baseline in Modified Rodnan Skin Score Over Time

  Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).

• Change From Baseline in UCLA SCTC GIT 2.0 Total Score Over Time

  Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit).

• Change From Baseline in UCLA SCTC GIT 2.0 Reflux Subscale Score Over Time

  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).

• Change From Baseline in UCLA SCTC GIT 2.0 Distension/Bloating Subscale Score Over Time

  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).

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Pomalidomide

EXPERIMENTAL

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.

Drug: Pomalidomide (CC-4047)

Interventions

Pomalidomide (CC-4047) DRUG

1 mg orally every day for 52 weeks

Pomalidomide

Placebo DRUG

Matching placebo capsules taken orally once a day

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Celgene: lead

Study Sites (56)

UCLA Division of Rheumatology

Los Angeles, California, 90095, United States

Location

Advances in Medicine

Rancho Mirage, California, 92270, United States

Location

Delaware Medical Care Associates, LLC

Newark, Delaware, 19713, United States

Location

Georgetown University School of Medicine

Washington D.C., District of Columbia, 20057, United States

Location

USF Health Faculty Office Building-FOB

Tampa, Florida, 33612, United States

Location

Arthritis Research and Treatment Center

Stockbridge, Georgia, 30281, United States

Location

University of Illinois at Chicago

Chicago, Illinois, 60612, United States

Location

LaPorte County Institute for Clinical Research, Inc

Michigan City, Indiana, 46360, United States

Location

University of Kentucky

Lexington, Kentucky, 40536-0284, United States

Location

Louisiana State University

Shreveport, Louisiana, 71103, United States

Location

Boston University of Medicine BUMC

Boston, Massachusetts, 02118, United States

Location

University of Michigan

Ann Arbor, Michigan, 48109, United States

Location

UMDNJ-Robert Wood Johnson Medical School Clinical Research Center

New Brunswick, New Jersey, 08903, United States

Location

North Shore-LIJ Health System-Division of Rheumatology

Great Neck, New York, 11021, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Toledo College of Medicine

Toledo, Ohio, 43614, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

University of Texas Health Science Center at Houston

Houston, Texas, 77030, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

The Prince Charles Hospital

Chermside, 4032, Australia

Location

The Queen Elizabeth Hospital

Woodville South, 5011, Australia

Location

CHRU de Lille FR

Lille, 59037, France

Location

Hopital Saint Louis

Paris, 75010, France

Location

Groupe Hospitalier Saint Vincent de Paul

Paris, 75014, France

Location

Kerckhoff-Klinik gGmbH

Bad Nauheim, 61231, Germany

Location

Charite - Universitätsmedizin Berlin

Berlin, 10117, Germany

Location

University of Erlangen-Nuremberg

Erlangen, 91054, Germany

Location

Klinikum der J.W. Gothe-Universitat Frankfurt

Frankfurt, 60590, Germany

Location

Rheumazentrum Ruhrgebiet

Herne, 44652, Germany

Location

University Hospital of Ulm

Ulm, 89081, Germany

Location

Azienda Ospedaliera Universitaria S. Martino di Genova

Genova, 16132, Italy

Location

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

Ospedale Luigi Sacco

Milan, 20157, Italy

Location

IRCCS Policlinico S. Matteo di Pavia

Pavia, 27100, Italy

Location

Azienda Ospedaliera Universitaria Pisana

Pisa, 56126, Italy

Location

Policlinico Umberto I

Roma, 00161, Italy

Location

Policlinico Universitario Agostino Gemelli

Roma, 00168, Italy

Location

Centrum Miriada Prywatny Gabinet Specjalistyczny Profesora Dra Stanislawa Sierakowskiego

Bialystok, 15-297, Poland

Location

Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, 85-168, Poland

Location

SPSK Nr 7 Slaskiego Uniwersytetu Medycznego, Oddzial Chorob Wewnetrznych i Reumatologii

Katowice, 40-634, Poland

Location

Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego Pomorskiego UM w Szczec

Szczecin, 71-252, Poland

Location

Instytut Reumatologii, Klinika i Poliklinika Ukladowych Chorób Tkanki Lacznej

Warsaw, 02-637, Poland

Location

Akademicki Szpital Kliniczny Klinika Reumatologii i Chorob Wewnetrznych

Wroclaw, 50-556, Poland

Location

Institution of the Russian Academy of Medical Sciences Research Institute of Rheumatology of the Ru

Moscow, 115522, Russia

Location

Penza Regional Clinical Hospital n.a. N.N. Burdenko

Penza, 440026, Russia

Location

St. Petersburg State Healthcare Institution "Clinical Rheumatology Hospital # 25"

Saint Petersburg, 190068, Russia

Location

Hospital Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Complejo Hospitalario de Santiago

Santiago de Compostela, 15706, Spain

Location

Hospital Universitario Dr. Peset

Valencia, 46017, Spain

Location

University Hospital Basel

Basel, 4031, Switzerland

Location

Chapel Allerton Hospital

Leeds, LS7 4SA, United Kingdom

Location

Royal Free Hospital

London, NW3 2PF, United Kingdom

Location

Royal Brompton Hospital - Interstitial Lung Disease Unit

London, SW3 6NP, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 29093152 BACKGROUND

• 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.

  BACKGROUND

MeSH Terms

Conditions

Scleroderma, Systemic; Lung Diseases, Interstitial

Interventions

pomalidomide

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases; Lung Diseases; Respiratory Tract Diseases

Limitations and Caveats

Based upon interim analysis data, the study did not meet its primary endpoints for subjects who had completed blinded treatment. The IDMC recommended the study be stopped due to lack of efficacy and the sponsor agreed with this recommendation.

Results Point of Contact

• Title: Clinical Trial Disclosure
• Organization: Celgene Corporation

ClinicalTrialDisclosure@Celgene.com

888-260-1599

Study Officials

• Shimon Korish, MD

  Celgene Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2012
• First Posted: March 21, 2012
• Study Start: August 9, 2012
• Primary Completion: November 3, 2016
• Study Completion: November 3, 2016
• Last Updated: December 1, 2023
• Results First Posted: October 18, 2019

Record last verified: 2023-11

Locations

ES (4); RU (3); GB (3); US (20); PL (6); AU (3); FR (3); IT (7); DE (6); CH (1)