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

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

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.

Study Overview

• Status: Terminated
• Conditions: Systemic Sclerosis; Scleroderma, Systemic; Systemic Scleroderma; Interstitial Lung Disease; Sclerosis, Systemic
• Intervention / Treatment: Drug: Placebo; Drug: Pomalidomide (CC-4047)

• Study Type: Interventional
• Enrollment (Actual): 23
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Chermside, Australia, 4032
    • The Prince Charles Hospital
  • Woodville South, Australia, 5011
    • The Queen Elizabeth Hospital
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Monash Medical Centre
• France
  • Lille, France, 59037
    • CHRU de Lille FR
  • Paris, France, 75010
    • Hôpital Saint louis
  • Paris, France, 75014
    • Groupe Hospitalier Saint Vincent de Paul
• Germany
  • Bad Nauheim, Germany, 61231
    • Kerckhoff-Klinik gGmbH
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Erlangen, Germany, 91054
    • University of Erlangen-Nuremberg
  • Frankfurt, Germany, 60590
    • Klinikum der J.W. Gothe-Universitat Frankfurt
  • Herne, Germany, 44652
    • Rheumazentrum Ruhrgebiet
  • Ulm, Germany, 89081
    • University Hospital of Ulm
• Italy
  • Genova, Italy, 16132
    • Azienda Ospedaliera Universitaria S. Martino di Genova
  • Milano, Italy, 20122
    • Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
  • Milano, Italy, 20157
    • Ospedale Luigi Sacco
  • Pavia, Italy, 27100
    • IRCCS Policlinico S. Matteo di Pavia
  • Pisa, Italy, 56126
    • Azienda Ospedaliera Universitaria Pisana
  • Roma, Italy, 00168
    • Policlinico Universitario Agostino Gemelli
  • Roma, Italy, 00161
    • Policlinico Umberto I
• Poland
  • Bialystok, Poland, 15-297
    • Centrum Miriada Prywatny Gabinet Specjalistyczny Profesora Dra Stanislawa Sierakowskiego
  • Bydgoszcz, Poland, 85-168
    • Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
  • Katowice, Poland, 40-634
    • SPSK Nr 7 Slaskiego Uniwersytetu Medycznego, Oddzial Chorob Wewnetrznych i Reumatologii
  • Szczecin, Poland, 71-252
    • Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego Pomorskiego UM w Szczec
  • Warszawa, Poland, 02-637
    • Instytut Reumatologii, Klinika i Poliklinika Ukladowych Chorób Tkanki Lacznej
  • Wroclaw, Poland, 50-556
    • Akademicki Szpital Kliniczny Klinika Reumatologii i Chorob Wewnetrznych
• Russian Federation
  • Moscow, Russian Federation, 115522
    • Institution of the Russian Academy of Medical Sciences Research Institute of Rheumatology of the Ru
  • Penza, Russian Federation, 440026
    • Penza Regional Clinical Hospital n.a. N.N. Burdenko
  • St. Petersburg, Russian Federation, 190068
    • St. Petersburg State Healthcare Institution "Clinical Rheumatology Hospital # 25"
• Spain
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de octubre
  • Madrid, Spain, 28007
    • Hospital Universitario Gregorio Marañón
  • Santiago de Compostela, Spain, 15706
    • Complejo Hospitalario de Santiago
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
• Switzerland
  • Basel, Switzerland, 4031
    • University Hospital Basel
• United Kingdom
  • Leeds, United Kingdom, LS7 4SA
    • Chapel Allerton Hospital
  • London, United Kingdom, NW3 2PF
    • Royal Free Hospital
  • London, United Kingdom, SW3 6NP
    • Royal Brompton Hospital - Interstitial Lung Disease Unit
• United States
  • California
    • Los Angeles, California, United States, 90095
      • UCLA Division of Rheumatology
    • Rancho Mirage, California, United States, 92270
      • Advances in Medicine
  • Delaware
    • Newark, Delaware, United States, 19713
      • Delaware Medical Care Associates, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20057
      • Georgetown University School of Medicine
  • Florida
    • Tampa, Florida, United States, 33612
      • USF Health Faculty Office Building-FOB
  • Georgia
    • Stockbridge, Georgia, United States, 30281
      • Arthritis Research and Treatment Center
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
  • Indiana
    • Michigan City, Indiana, United States, 46360
      • LaPorte County Institute for Clinical Research, Inc
  • Kentucky
    • Lexington, Kentucky, United States, 40536-0284
      • University of Kentucky
  • Louisiana
    • Shreveport, Louisiana, United States, 71103
      • Louisiana State University
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston University of Medicine BUMC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New Jersey
    • New Brunswick, New Jersey, United States, 08903
      • UMDNJ-Robert Wood Johnson Medical School Clinical Research Center
  • New York
    • Great Neck, New York, United States, 11021
      • North Shore-LIJ Health System-Division of Rheumatology
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
    • Toledo, Ohio, United States, 43614
      • University of Toledo College of Medicine
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15261
      • University of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas Health Science Center at Houston
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo capsules taken orally once a day
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.	Drug: Pomalidomide (CC-4047); 1 mg orally every day for 52 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Percent Predicted Forced Vital Capacity Over Time	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).	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	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 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	The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets 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 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	The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets 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. The reflux subscale score is calculated as the average of eight reflux-related questions; the score ranges from 0 to 3, where higher scores indicate more frequent symptoms.	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	The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets 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. The distension/bloating subscale score is calculated as the average of four distension/bloating-related questions; the score ranges from 0 to 3, where higher scores indicate more frequent symptoms.	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 Fecal Soilage Subscale Score Over Time	The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets 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. The fecal soilage subscale score is calculated from one soilage question; the score ranges from 0 to 3, where higher scores indicate more frequent symptoms.	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 Diarrhea Subscale Score Over Time	The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets 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 diarrhea subscale score is calculated as the average of one diarrhea question about the frequency of loose stools (on a scale from 0 [none] to 3 [5-7 days/week] and one question about the presence of watery stools (scored as 0 [No] or 1 [Yes]); the score ranges from 0 to 2, where a higher score indicates more frequent symptoms.	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 Social Functioning Subscale Score Over Time	The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets 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. The social functioning subscale score is calculated as the average of six questions about how often symptoms interfered with social activities; the score ranges from 0 to 3, where higher scores indicate more frequent symptoms.	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 Emotional Well Being Subscale Score Over Time	The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets 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. The emotional well-being subscale score is calculated as the average of nine questions regarding the impact of bowel problems on emotional status; the score ranges from 0 to 3, where higher scores indicate more frequent problems.	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 Constipation Subscale Score Over Time	The UCLA SCTC GIT 2.0 is a 34-item, health-related quality of life self-administered evaluation tool, which targets 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. The constipation subscale score is calculated as the average of three questions regarding the frequency of constipation (scored from 0 [no days] to 3 [5-7 days/week] and one question about the presence of stools becoming harder (scored as 0 [No] or 1 [Yes]); the score ranges from 0 to 2.5, where higher scores indicate more frequent symptoms.	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 Dyspnea Functional Impairment at Week 12	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath.	Week 12
Change From Baseline in Dyspnea Functional Impairment at Week 24	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath.	Week 24
Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath.	Week 52 or at the Treatment Phase Early Termination visit
Change From Baseline in Dyspnea Functional Impairment at Week 64	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath.	Week 64
Change From Baseline in Dyspnea Functional Impairment at Week 76	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath.	Week 76
Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. Changes in dyspnea functional impairment were assessed on a scale from Major Deterioration (formerly working but had to stop working and abandoned usual activities due to shortness of breath) to Major Improvement (able to return to work at former pace and return to full activities with only mild restriction due to improvement of shortness of breath). Further impairment for other reasons includes participants who gave up or reduced work or other activities for reasons other than shortness of breath.	Week 156 or the Extension Phase Early Termination visit
Change From Baseline in Dyspnea Magnitude of Task at Week 12	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain.	Week 12
Change From Baseline in Dyspnea Magnitude of Task at Week 24	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain.	Week 24
Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain.	Week 52 or at the Treatment Phase Early Termination visit
Change From Baseline in Dyspnea Magnitude of Task at Week 64	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain.	Week 64
Change From Baseline in Dyspnea Magnitude of Task at Week 76	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carrying very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain.	Week 76
Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with extraordinary activity such as running or carry very heavy loads). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (deteriorated ≥ 2 grades from Baseline) to Major Improvement (Improved ≥ 2 grades from Baseline). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath, for example musculoskeletal problems or chest pain.	Week 156 or the Extension Phase Early Termination visit
Change From Baseline in Dyspnea Magnitude of Effort at Week 12	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath.	Week 12
Change From Baseline in Dyspnea Magnitude of Effort at Week 24	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath.	Week 24
Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath.	Week 52 or at the Treatment Phase Early Termination visit
Change From Baseline in Dyspnea Magnitude of Effort at Week 64	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath.	Week 64
Change From Baseline in Dyspnea Magnitude of Effort at Week 76	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath.	Week 76
Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination	The Transition Dyspnea Index (TDI) provides interview-based measurements of breathlessness related to activities of daily living. The TDI is an evaluative instrument that includes specific criteria for each of three components (functional impairment, magnitude of task and magnitude of effort) to measure changes from a baseline state. At Baseline magnitude of task was assessed on a scale from Grade 0 (becomes short of breath at rest, while sitting or lying) to Grade 4 (becomes short of breath only with greatest imaginable effort). Changes in dyspnea magnitude of task were assessed on a scale from Major Deterioration (severe decrease in effort from Baseline to avoid shortness of breath, activities take 50-100% longer to complete) to Major Improvement (able to do things with much greater effort than previously with few, if any, pauses). Further impairment for other reasons includes participants with reduced exertion capacity for reasons other than shortness of breath.	Week 156 or at the Extension Phase Early Termination visit
Oxygen Saturation Over Time	Oxygen saturation was measured by pulse oximetry.	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).
Pharmacokinetic Parameters of Pomalidomide in Plasma	Pharmacokinetic (PK) analyses were not conducted as there were too few participants with available data.	Day 1 and week 4 pre-dose and up to 24 hours post-dose.

Collaborators and Investigators

• Sponsor: Celgene
• Investigators: Study Director: Shimon Korish, MD, Celgene Corporation

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2012
• Primary Completion (Actual): November 3, 2016
• Study Completion (Actual): November 3, 2016

Study Registration Dates

• First Submitted: March 19, 2012
• First Submitted That Met QC Criteria: March 20, 2012
• First Posted (Estimated): March 21, 2012

Study Record Updates

• Last Update Posted (Actual): December 1, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Respiratory Tract Diseases; Connective Tissue Diseases; Sclerosis; Lung Diseases; Scleroderma, Systemic; Scleroderma, Diffuse; Lung Diseases, Interstitial; Scleroderma, Localized; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Pomalidomide
• Other Study ID Numbers: CC-4047-SSC-001; 2010-023047-15 (EudraCT Number)