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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01559129
Recruitment Status : Terminated (Enrollment was stopped early (see limitations and caveats section).)
First Posted : March 21, 2012
Results First Posted : October 18, 2019
Last Update Posted : October 18, 2019
Sponsor:
Information provided by (Responsible Party):
Celgene

Tracking Information
First Submitted Date  ICMJE March 19, 2012
First Posted Date  ICMJE March 21, 2012
Results First Submitted Date  ICMJE November 3, 2017
Results First Posted Date  ICMJE October 18, 2019
Last Update Posted Date October 18, 2019
Actual Study Start Date  ICMJE August 9, 2012
Actual Primary Completion Date November 3, 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2019)
  • Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: 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. ]
    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.
  • Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 [ Time Frame: Baseline (defined as the average of all values between Screening and Baseline) and Weeks 48 and 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.
  • Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52/Early Termination [ Time Frame: Baseline and Week 52 (or the Treatment Phase Early Termination visit) ]
    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.
  • 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 [ Time Frame: Baseline and Week 52 (or Treatment Phase Early Termination visit) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 20, 2012)
  • Evaluation of the number of subjects with pomalidomide-related adverse events [ Time Frame: Up to 56 weeks ]
    Evaluation of the number of subjects with pomalidomide-related adverse events
  • Change from Baseline (Week 0) of the forced vital capacity (FVC) at Week 52 [ Time Frame: 52 weeks ]
    Change from Baseline (Week 0) of the forced vital capacity (FVC) at Week 52
  • Change from Baseline (Week 0) of the modified Rodnan Skin Score (mRSS)at Week 52 [ Time Frame: 52 weeks ]
    Change from Baseline (Week 0) of the modified Rodnan Skin Score (mRSS)at Week 52
  • Change from Baseline of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) total score [ Time Frame: 52 weeks ]
    Change from Baseline (Week 0) of the UCLA Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) total score
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2019)
  • Change From Baseline in Percent Predicted Forced Vital Capacity Over Time [ Time Frame: Baseline (defined as the average of all values between Screening and Baseline) and Weeks 12, 24, 36, 64, 76, and 156 ]
    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).
  • Change From Baseline in Modified Rodnan Skin Score Over Time [ Time Frame: Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit). ]
    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.
  • Change From Baseline in UCLA SCTC GIT 2.0 Total Score Over Time [ Time Frame: Baseline and Weeks 12, 24, 64, 76, and 156 (or the Extension Phase Early Termination visit). ]
    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.
  • Change From Baseline in UCLA SCTC GIT 2.0 Reflux Subscale Score Over Time [ Time Frame: 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). ]
    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.
  • Change From Baseline in UCLA SCTC GIT 2.0 Distension/Bloating Subscale Score Over Time [ Time Frame: 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). ]
    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.
  • Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time [ Time Frame: 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). ]
    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.
  • Change From Baseline in UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time [ Time Frame: 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). ]
    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.
  • Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time [ Time Frame: 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). ]
    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.
  • Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time [ Time Frame: 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). ]
    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.
  • Change From Baseline in UCLA SCTC GIT 2.0 Constipation Subscale Score Over Time [ Time Frame: 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). ]
    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.
  • Change From Baseline in Dyspnea Functional Impairment at Week 12 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Functional Impairment at Week 24 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination [ Time Frame: Week 52 or at the Treatment Phase Early Termination visit ]
    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.
  • Change From Baseline in Dyspnea Functional Impairment at Week 64 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Functional Impairment at Week 76 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination [ Time Frame: Week 156 or the Extension Phase Early Termination visit ]
    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.
  • Change From Baseline in Dyspnea Magnitude of Task at Week 12 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Magnitude of Task at Week 24 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination [ Time Frame: Week 52 or at the Treatment Phase Early Termination visit ]
    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.
  • Change From Baseline in Dyspnea Magnitude of Task at Week 64 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Magnitude of Task at Week 76 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination [ Time Frame: Week 156 or the Extension Phase Early Termination visit ]
    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.
  • Change From Baseline in Dyspnea Magnitude of Effort at Week 12 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Magnitude of Effort at Week 24 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination [ Time Frame: Week 52 or at the Treatment Phase Early Termination visit ]
    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.
  • Change From Baseline in Dyspnea Magnitude of Effort at Week 64 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Magnitude of Effort at Week 76 [ Time Frame: 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.
  • Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination [ Time Frame: Week 156 or at the Extension Phase Early Termination visit ]
    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.
  • Oxygen Saturation Over Time [ Time Frame: 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). ]
    Oxygen saturation was measured by pulse oximetry.
  • Pharmacokinetic Parameters of Pomalidomide in Plasma [ Time Frame: Day 1 and week 4 pre-dose and up to 24 hours post-dose. ]
    Pharmacokinetic (PK) analyses were not conducted as there were too few participants with available data.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 20, 2012)
  • Estimation of pomalidomide pharmacokinetic (PK) parameters in plasma, AUCt [ Time Frame: Up to 8 weeks ]
    Estimation of pomalidomide pharmacokinetic (PK) parameters in plasma, AUCt
  • Estimation of pomalidomide PK parameters in plasma, Cmax [ Time Frame: Up to 8 weeks ]
    Estimation of pomalidomide PK parameters in plasma, Cmax
  • Estimation of pomalidomide PK parameters in plasma, Tmax [ Time Frame: Up to 8 weeks ]
    Estimation of pomalidomide PK parameters in plasma, Tmax
  • Change from Baseline (Week 0) of the FVC [ Time Frame: Up to 48 weeks ]
    Change from Baseline (Week 0) of the FVC
  • Change from Baseline (Week 0) of the Modified Rodnan Skin Score [ Time Frame: Up to 24 weeks ]
    Change from Baseline (Week 0) of the Modified Rodnan Skin Score
  • Change from Baseline (Week 0) of the UCLA SCTC GIT 2.0 total score [ Time Frame: Up to 24 weeks ]
    Change from Baseline (Week 0) of the UCLA SCTC GIT 2.0 total score
  • Change from Baseline (Week 0) UCLA SCTC GIT 2.0 subscale scores (Reflux, Distention/Bloating, Fecal Soilage, Diarrhea, Social functioning, Emotional Well-being and Constipation) [ Time Frame: Up to 52 weeks ]
    Change from Baseline (Week 0) UCLA SCTC GIT 2.0 subscale scores (Reflux, Distention/Bloating, Fecal Soilage, Diarrhea, Social functioning, Emotional Well-being and Constipation)
  • Change from Baseline (Week 0) of the oxygen saturation (as measured by pulse oximetry) [ Time Frame: Up to 52 weeks ]
    Change from Baseline (Week 0) of the oxygen saturation (as measured by pulse oximetry)
  • Change from Baseline (Week 0) dyspnea (as measured by the Transition Dyspnea Index) [ Time Frame: Up to 52 weeks ]
    Change from Baseline (Week 0) dyspnea (as measured by the Transition Dyspnea Index)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of Pomalidomide (CC-4047) to Evaluate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Effectiveness for Patients With Systemic Sclerosis With Interstitial Lung Disease
Official Title  ICMJE 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
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Scleroderma, Systemic
  • Sclerosis, Systemic
  • Systemic Scleroderma
  • Systemic Sclerosis
  • Interstitial Lung Disease
Intervention  ICMJE
  • Drug: Pomalidomide (CC-4047)
    1 mg orally every day for 52 weeks
  • Drug: Placebo
    Matching placebo capsules taken orally once a day
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Intervention: Drug: 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.
    Intervention: Drug: Pomalidomide (CC-4047)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: June 18, 2014)
23
Original Estimated Enrollment  ICMJE
 (submitted: March 20, 2012)
88
Actual Study Completion Date  ICMJE November 3, 2016
Actual Primary Completion Date November 3, 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key 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:

    • 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] OR
    • FVC readings ≥ 70% and ≤ 80% at Screening and Baseline (Visit 2) with a documented history of either or both of:

      1. A ≥ 5% decrease (expressed as percent predicted or in liters) in FVC in the 24-month period prior to Baseline (Visit 2) based on 3 or more assessments. Two assessments may be done during the Screening phase provided the assessments are completed at least 2 weeks apart.
      2. A high resolution computed tomography (HRCT) fibrosis score > 20%
  • 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.

Key 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   Italy,   Poland,   Russian Federation,   Spain,   Switzerland,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01559129
Other Study ID Numbers  ICMJE CC-4047-SSC-001
2010-023047-15 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Celgene
Original Responsible Party Celgene Corporation
Current Study Sponsor  ICMJE Celgene
Original Study Sponsor  ICMJE Celgene Corporation
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Shimon Korish, MD Celgene Corporation
PRS Account Celgene
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP