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

• ClinicalTrials.gov Identifier: NCT01559129
• Recruitment Status: Terminated
• First Posted: March 21, 2012
• Results First Posted: October 18, 2019
• Last Update Posted: October 18, 2019
• Sponsor: Celgene
• Information provided by (Responsible Party): Celgene

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Scleroderma, Systemic; Sclerosis, Systemic; Systemic Scleroderma; Systemic Sclerosis; Interstitial Lung Disease	Drug: Pomalidomide (CC-4047); Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 23 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase 2, Proof-Of-Concept, Multicenter, Randomized, Double-Blind, Placebo- Controlled, Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Efficacy of Pomalidomide (CC-4047) in Subjects With Systemic Sclerosis With Interstitial Lung Disease
• Actual Study Start Date: August 9, 2012
• Actual Primary Completion Date: November 3, 2016
• Actual Study Completion Date: November 3, 2016

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.

Secondary Outcome Measures :

1. 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).
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Locations

United States, California

UCLA Division of Rheumatology

Los Angeles, California, United States, 90095

Advances in Medicine

Rancho Mirage, California, United States, 92270

United States, Delaware

Delaware Medical Care Associates, LLC

Newark, Delaware, United States, 19713

United States, District of Columbia

Georgetown University School of Medicine

Washington, District of Columbia, United States, 20057

United States, Florida

USF Health Faculty Office Building-FOB

Tampa, Florida, United States, 33612

United States, Georgia

Arthritis Research and Treatment Center

Stockbridge, Georgia, United States, 30281

United States, Illinois

University of Illinois at Chicago

Chicago, Illinois, United States, 60612

United States, Indiana

LaPorte County Institute for Clinical Research, Inc

Michigan City, Indiana, United States, 46360

United States, Kentucky

University of Kentucky

Lexington, Kentucky, United States, 40536-0284

United States, Louisiana

Louisiana State University

Shreveport, Louisiana, United States, 71103

United States, Massachusetts

Boston University of Medicine BUMC

Boston, Massachusetts, United States, 02118

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, New Jersey

UMDNJ-Robert Wood Johnson Medical School Clinical Research Center

New Brunswick, New Jersey, United States, 08903

United States, New York

North Shore-LIJ Health System-Division of Rheumatology

Great Neck, New York, United States, 11021

United States, Ohio

Cleveland Clinic

Cleveland, Ohio, United States, 44195

University of Toledo College of Medicine

Toledo, Ohio, United States, 43614

United States, Pennsylvania

University of Pennsylvania

Philadelphia, Pennsylvania, United States, 19104

University of Pittsburgh

Pittsburgh, Pennsylvania, United States, 15261

United States, Texas

University of Texas Health Science Center at Houston

Houston, Texas, United States, 77030

United States, Wisconsin

Medical College of Wisconsin

Milwaukee, Wisconsin, United States, 53226

Australia, Victoria

Monash Medical Centre

Clayton, Victoria, Australia, 3168

Australia

The Prince Charles Hospital

Chermside, Australia, 4032

The Queen Elizabeth Hospital

Woodville South, Australia, 5011

France

CHRU de Lille FR

Lille, France, 59037

Hopital Saint Louis

Paris, France, 75010

Groupe Hospitalier Saint Vincent de Paul

Paris, France, 75014

Germany

Kerckhoff-Klinik gGmbH

Bad Nauheim, Germany, 61231

Charite - Universitätsmedizin Berlin

Berlin, Germany, 10117

University of Erlangen-Nuremberg

Erlangen, Germany, 91054

Klinikum der J.W. Gothe-Universitat Frankfurt

Frankfurt, Germany, 60590

Rheumazentrum Ruhrgebiet

Herne, Germany, 44652

University Hospital of Ulm

Ulm, Germany, 89081

Italy

Azienda Ospedaliera Universitaria S. Martino di Genova

Genova, Italy, 16132

Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico

Milano, Italy, 20122

Ospedale Luigi Sacco

Milano, Italy, 20157

IRCCS Policlinico S. Matteo di Pavia

Pavia, Italy, 27100

Azienda Ospedaliera Universitaria Pisana

Pisa, Italy, 56126

Policlinico Umberto I

Roma, Italy, 00161

Policlinico Universitario Agostino Gemelli

Roma, Italy, 00168

Poland

Centrum Miriada Prywatny Gabinet Specjalistyczny Profesora Dra Stanislawa Sierakowskiego

Bialystok, Poland, 15-297

Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy

Bydgoszcz, Poland, 85-168

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

Katowice, Poland, 40-634

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

Szczecin, Poland, 71-252

Instytut Reumatologii, Klinika i Poliklinika Ukladowych Chorób Tkanki Lacznej

Warszawa, Poland, 02-637

Akademicki Szpital Kliniczny Klinika Reumatologii i Chorob Wewnetrznych

Wroclaw, Poland, 50-556

Russian Federation

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

Moscow, Russian Federation, 115522

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

Penza, Russian Federation, 440026

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

St. Petersburg, Russian Federation, 190068

Spain

Hospital Universitario Gregorio Maranon

Madrid, Spain, 28007

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Complejo Hospitalario de Santiago

Santiago de Compostela, Spain, 15706

Hospital Universitario Dr. Peset

Valencia, Spain, 46017

Switzerland

University Hospital Basel

Basel, Switzerland, 4031

United Kingdom

Chapel Allerton Hospital

Leeds, United Kingdom, LS7 4SA

Royal Free Hospital

London, United Kingdom, NW3 2PF

Royal Brompton Hospital - Interstitial Lung Disease Unit

London, United Kingdom, SW3 6NP

Sponsors and Collaborators

Celgene

Investigators

• Study Director: Shimon Korish, MD; Celgene Corporation

More Information

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.

• Responsible Party: Celgene
• ClinicalTrials.gov Identifier: NCT01559129
• Other Study ID Numbers: CC-4047-SSC-001; 2010-023047-15 ( EudraCT Number )
• First Posted: March 21, 2012
• Results First Posted: October 18, 2019
• Last Update Posted: October 18, 2019
• Last Verified: October 2019

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Interstitial; Scleroderma, Systemic; Scleroderma, Diffuse; Scleroderma, Localized; Sclerosis; Pathologic Processes; Respiratory Tract Diseases; Connective Tissue Diseases; Skin Diseases; Pomalidomide; Immunologic Factors; Physiological Effects of Drugs; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Antineoplastic Agents