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

Phase 2

Terminated

Conditions: Scleroderma, Systemic
Interstitial Lung Disease
Sclerosis, Systemic
Systemic Sclerosis
Systemic Scleroderma

Interventions: Drug: Placebo
Drug: Pomalidomide (CC-4047)

Registration Number: NCT01559129

Lead Sponsor: Celgene

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 available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 23

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Pomalidomide	Pomalidomide (CC-4047)	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	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 University of California, Los Angeles, Scleroderma Clinical Trial Consortium Gastrointestinal Tract (UCLA SCTC GIT 2.0) Total Score at Week 52/Early Termination	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.
Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52	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	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Percent Predicted Forced Vital Capacity Over Time	Baseline (defined as the average of all values between Screening and Baseline) and Weeks 12, 24, 36, 64, 76, and 156	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	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	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 Distension/Bloating Subscale Score Over Time	Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).	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	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 Social Functioning Subscale Score Over Time	Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).	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	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 Reflux Subscale Score Over Time	Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).	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 Constipation Subscale Score Over Time	Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).	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 156/Early Termination	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	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 UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time	Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).	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 Dyspnea Functional Impairment at Week 52/Early Termination	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	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 12	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	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 76	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 Magnitude of Task at Week 24	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 76	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 52/Early Termination	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	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 156/Early Termination	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	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.
Pharmacokinetic Parameters of Pomalidomide in Plasma	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.
Change From Baseline in Dyspnea Magnitude of Effort at Week 24	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	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 76	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 64	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.
Oxygen Saturation Over Time	Baseline and Weeks 12, 24, 52 (or at the Treatment Phase Early Termination visit), 64, 76, and 156 (or the Extension Phase Early Termination visit).	Oxygen saturation was measured by pulse oximetry.
Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination	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.

Trial Locations

Locations (56): Monash Medical Centre
🇦🇺
Clayton, Victoria, Australia
SPSK Nr 7 Slaskiego Uniwersytetu Medycznego, Oddzial Chorob Wewnetrznych i Reumatologii
🇵🇱
Katowice, Poland
Instytut Reumatologii, Klinika i Poliklinika Ukladowych Chorób Tkanki Lacznej
🇵🇱
Warszawa, Poland
Penza Regional Clinical Hospital n.a. N.N. Burdenko
🇷🇺
Penza, Russian Federation
Delaware Medical Care Associates, LLC
🇺🇸
Newark, Delaware, United States
St. Petersburg State Healthcare Institution "Clinical Rheumatology Hospital # 25"
🇷🇺
St. Petersburg, Russian Federation
Institution of the Russian Academy of Medical Sciences Research Institute of Rheumatology of the Ru
🇷🇺
Moscow, Russian Federation
Louisiana State University
🇺🇸
Shreveport, Louisiana, United States
UMDNJ-Robert Wood Johnson Medical School Clinical Research Center
🇺🇸
New Brunswick, New Jersey, United States
Charite - Universitätsmedizin Berlin
🇩🇪
Berlin, Germany
North Shore-LIJ Health System-Division of Rheumatology
🇺🇸
Great Neck, New York, United States
Hopital Saint Louis
🇫🇷
Paris, France
University of Kentucky
🇺🇸
Lexington, Kentucky, United States
University of Michigan
🇺🇸
Ann Arbor, Michigan, United States
Georgetown University School of Medicine
🇺🇸
Washington, District of Columbia, United States
University Hospital of Ulm
🇩🇪
Ulm, Germany
Hospital Universitario Gregorio Maranon
🇪🇸
Madrid, Spain
Rheumazentrum Ruhrgebiet
🇩🇪
Herne, Germany
University of Erlangen-Nuremberg
🇩🇪
Erlangen, Germany
Chapel Allerton Hospital
🇬🇧
Leeds, United Kingdom
Szpital Uniwersytecki nr 2 im. Dr Jana Biziela w Bydgoszczy
🇵🇱
Bydgoszcz, Poland
Akademicki Szpital Kliniczny Klinika Reumatologii i Chorob Wewnetrznych
🇵🇱
Wroclaw, Poland
Complejo Hospitalario de Santiago
🇪🇸
Santiago de Compostela, Spain
Azienda Ospedaliera Universitaria S. Martino di Genova
🇮🇹
Genova, Italy
Centrum Miriada Prywatny Gabinet Specjalistyczny Profesora Dra Stanislawa Sierakowskiego
🇵🇱
Bialystok, Poland
Samodzielny Publiczny Szpital Kliniczny nr 1 im. prof.Tadeusza Sokolowskiego Pomorskiego UM w Szczec
🇵🇱
Szczecin, Poland
Hospital Universitario Dr. Peset
🇪🇸
Valencia, Spain
University Hospital Basel
🇨🇭
Basel, Switzerland
Hospital Universitario 12 de Octubre
🇪🇸
Madrid, Spain
Royal Free Hospital
🇬🇧
London, United Kingdom
Ospedale Luigi Sacco
🇮🇹
Milano, Italy
IRCCS Policlinico S. Matteo di Pavia
🇮🇹
Pavia, Italy
Azienda Ospedaliera Universitaria Pisana
🇮🇹
Pisa, Italy
Policlinico Umberto I
🇮🇹
Roma, Italy
Policlinico Universitario Agostino Gemelli
🇮🇹
Roma, Italy
Boston University of Medicine BUMC
🇺🇸
Boston, Massachusetts, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
University of Texas Health Science Center at Houston
🇺🇸
Houston, Texas, United States
Medical College of Wisconsin
🇺🇸
Milwaukee, Wisconsin, United States
UCLA Division of Rheumatology
🇺🇸
Los Angeles, California, United States
Advances in Medicine
🇺🇸
Rancho Mirage, California, United States
Kerckhoff-Klinik gGmbH
🇩🇪
Bad Nauheim, Germany
University of Illinois at Chicago
🇺🇸
Chicago, Illinois, United States
USF Health Faculty Office Building-FOB
🇺🇸
Tampa, Florida, United States
LaPorte County Institute for Clinical Research, Inc
🇺🇸
Michigan City, Indiana, United States
Arthritis Research and Treatment Center
🇺🇸
Stockbridge, Georgia, United States
University of Toledo College of Medicine
🇺🇸
Toledo, Ohio, United States
University of Pennsylvania
🇺🇸
Philadelphia, Pennsylvania, United States
University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
The Queen Elizabeth Hospital
🇦🇺
Woodville South, Australia
The Prince Charles Hospital
🇦🇺
Chermside, Australia
CHRU de Lille FR
🇫🇷
Lille, France
Groupe Hospitalier Saint Vincent de Paul
🇫🇷
Paris, France
Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
🇮🇹
Milano, Italy
Klinikum der J.W. Gothe-Universitat Frankfurt
🇩🇪
Frankfurt, Germany
Royal Brompton Hospital - Interstitial Lung Disease Unit
🇬🇧
London, United Kingdom