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Clinical Trial Results:
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

Summary
EudraCT number	2010-023047-15
Trial protocol	DE GB IT ES PL
Global end of trial date	03 Nov 2016

Results information
Results version number	v1(current)
This version publication date	19 Nov 2017
First version publication date	19 Nov 2017
Other versions

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

CC-4047-SSC-001

ISRCTN number

US NCT number

NCT01559129

WHO universal trial number (UTN)

Sponsor organisation name

Celgene Corporation

Sponsor organisation address

86 Morris Avenue, Summit, NJ, United States, 07901

Public contact

ClinicalTrialDisclosure, Celgene Corporation, +1 8882601599, ClinicalTrialDisclosure@celgene.com

Scientific contact

Shimon Korish, MD, Celgene Corporation, +1 908-897-6350, Skorish@Celgene.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Analysis stage

Final

Date of interim/final analysis

17 Sep 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

03 Nov 2016

Was the trial ended prematurely?

Yes

Main objective of the trial

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.

Protection of trial subjects

This study was conducted in accordance with the guidelines of current Good Clinical Practice including the archiving of essential documents.

Background therapy

Evidence for comparator

Actual start date of recruitment

08 Aug 2012

Long term follow-up planned

Yes

Long term follow-up rationale

Safety

Long term follow-up duration

4 Years

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Australia: 2

Country: Number of subjects enrolled

France: 1

Country: Number of subjects enrolled

Germany: 1

Country: Number of subjects enrolled

Poland: 1

Country: Number of subjects enrolled

Russian Federation: 6

Country: Number of subjects enrolled

Spain: 1

Country: Number of subjects enrolled

United Kingdom: 2

Country: Number of subjects enrolled

United States: 9

Worldwide total number of subjects

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Screening details

Participants were randomized in a 1:1 ratio to receive either pomalidomide 1 mg daily or matching placebo. Randomization was stratified based on type of systemic sclerosis (limited [lSSc] versus diffuse [dSSc]).

Period 1 title

Treatment Phase

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received placebo orally once a day for 52 weeks during the treatment phase.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Placebo capsules taken orally once a day

Pomalidomide

Arm description

Participants received 1 mg pomalidomide orally once a day for 52 weeks during the treatment phase.

Arm type

Experimental

Investigational medicinal product name

Pomalidomide

Investigational medicinal product code

CC-4047

Other name

POMALYST®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Pomalidomide capsules taken orally once a day

Number of subjects in period 1	Placebo	Pomalidomide
Started	12	11
Received Treatment	12	10
Completed	7	4
Not completed	5	7
Protocol exclusion criteria	1	-
Study terminated by sponsor	3	2
Adverse event	-	2
Did not receive study drug	-	1
Progressive disease	1	1
Lack of efficacy	-	1

Period 2 title

Open-label Extension Period

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Placebo/Pomalidomide

Arm description

Participants who received placebo orally once a day for 52 weeks during the treatment phase transitioned to receive 1 mg pomalidomide orally once a day for up to 2 years during the open-label extension period.

Arm type

Experimental

Investigational medicinal product name

Pomalidomide

Investigational medicinal product code

CC-4047

Other name

POMALYST®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Pomalidomide capsules taken orally once a day

Pomalidomide/Pomalidomide

Arm description

Participants who received 1 mg pomalidomide orally once a day for 52 weeks during the treatment phase continued to receive the same treatment for up to 2 years during the open-label extension phase.

Arm type

Experimental

Investigational medicinal product name

Pomalidomide

Investigational medicinal product code

CC-4047

Other name

POMALYST®

Pharmaceutical forms

Capsule

Routes of administration

Oral use

Dosage and administration details

Pomalidomide capsules taken orally once a day

Number of subjects in period 2 ^[1]	Placebo/Pomalidomide	Pomalidomide/Pomalidomide
Started	6	2
Completed	0	0
Not completed	6	2
Adverse event	1	-
Study terminated by sponsor	5	2

Notes
[1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: Three participants who completed the treatment phase elected not to enter the open-label extension phase.

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants received placebo orally once a day for 52 weeks during the treatment phase.

Reporting group title

Pomalidomide

Reporting group description

Participants received 1 mg pomalidomide orally once a day for 52 weeks during the treatment phase.

Reporting group values	Placebo	Pomalidomide	Total
Number of subjects	12	11	23
Age categorical
Units: Subjects
Adults (18-64 years)	10	10	20
From 65-84 years	2	1	3
85 years and over	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	44.8 ± 13.77	48.9 ± 9.84	-
Gender categorical
Units: Subjects
Female	10	10	20
Male	2	1	3
Race
Units: Subjects
Asian	0	2	2
Black or African American	0	1	1
Native Hawaiian or Other Pacific Islanders	1	0	1
White	10	8	18
Other	1	0	1
Body Mass Index (BMI)
Units: kg/m^2
arithmetic mean (standard deviation)	30.64 ± 5.392	27.61 ± 9.4	-

End points

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Reporting group title

Placebo

Reporting group description

Participants received placebo orally once a day for 52 weeks during the treatment phase.

Reporting group title

Pomalidomide

Reporting group description

Participants received 1 mg pomalidomide orally once a day for 52 weeks during the treatment phase.

Reporting group title

Placebo/Pomalidomide

Reporting group description

Reporting group title

Pomalidomide/Pomalidomide

Reporting group description

Participants who received 1 mg pomalidomide orally once a day for 52 weeks during the treatment phase continued to receive the same treatment for up to 2 years during the open-label extension phase.

Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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End point title

Number of Participants With Treatment-emergent Adverse Events (TEAEs) ^[1]

End point description

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

End point type

Primary

End point timeframe

From the start of study drug to 28 days after last dose; Treatment Phase median duration of treatment was 358 for Placebo and 320 days for Pomalidomide; Extension phase median duration of treatment was 161 days for Placebo and 194 days for pomalidomide.

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed due to the low number of subjects enrolled.

End point values	Placebo	Placebo/Pomalidomide	Pomalidomide	Pomalidomide/Pomalidomide
Number of subjects analysed	12	6	10	2
Units: participants
Any TEAE	12	5	9	2
Drug-related TEAE	8	3	6	1
Severe TEAE	1	0	4	0
Serious TEAE	1	0	4	1
Serious Drug-related TEAE	0	0	1	0
TEAE Leading to Drug Interruption	2	0	1	0
TEAE Leading to Drug Withdrawal	0	0	4	0
TEAE Leading to Death	0	0	0	0

No statistical analyses for this end point

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

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End point title

Change From Baseline in Percent Predicted Forced Vital Capacity (FVC) at Week 52 ^[2]

End point description

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. The Full Analysis Set (FAS) consisted of all randomized participants who received at least one dose of study drug. Participants with a Baseline value and a Week 52 were included in the analysis.

End point type

Primary

End point timeframe

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

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed due to the low number of subjects enrolled.

End point values	Placebo	Pomalidomide
Number of subjects analysed	11	8
Units: percent predicted
arithmetic mean (standard deviation)	-2.8 ± 4.02	-5.2 ± 5.29

No statistical analyses for this end point

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

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End point title

Change From Baseline in the Modified Rodnan Skin Score (mRSS) at Week 52/Early Termination ^[3]

End point description

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.

End point type

Primary

End point timeframe

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

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed due to the low number of subjects enrolled.

End point values	Placebo	Pomalidomide
Number of subjects analysed	11 ^[4]	10 ^[5]
Units: units on a scale
arithmetic mean (standard deviation)	-3.7 ± 6.99	-2.7 ± 5.66

Notes
[4] - FAS participants with a Baseline value and a post-baseline value at Week 52 or Early Termination
[5] - FAS participants with a Baseline value and a post-baseline value at Week 52 or Early Termination

No statistical analyses for this end point

Primary: 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

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End point title

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 ^[6]

End point description

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.

End point type

Primary

End point timeframe

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

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: No statistical analyses were performed due to the low number of subjects enrolled.

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[7]	10 ^[8]
Units: units on a scale
arithmetic mean (standard deviation)	0.0 ± 0.18	0.1 ± 0.29

Notes
[7] - FAS participants with a Baseline value and a post-baseline value at Week 52 or Early Termination
[8] - FAS participants with a Baseline value and a post-baseline value at Week 52 or Early Termination

No statistical analyses for this end point

Secondary: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time

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End point title

Change From Baseline in Percent Predicted Forced Vital Capacity Over Time

End point description

End point type

Secondary

End point timeframe

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

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[9]	10 ^[10]
Units: percent predicted
arithmetic mean (standard deviation)
Week 12 (n = 10, 8)	-2.4 ± 3.07	-1.8 ± 3.39
Week 24 (n = 10, 8)	-1.3 ± 3.33	2.3 ± 12.58
Week 36 (n = 9, 6)	-2.6 ± 2.48	-4.4 ± 3.97
Week 64 (n = 6, 2)	-7.0 ± 4.29	-6.4 ± 4.49
Week 76 (n = 2, 1)	-8.7 ± 10.34	-5.2 ± 99999
Week 156 (n = 4, 2)	-6.7 ± 6.19	-5.9 ± 2.31

Notes
[9] - FAS participants with a Baseline value and post-baseline value at the time point.
[10] - FAS participants with a Baseline value and post-baseline value at the time point.

No statistical analyses for this end point

Secondary: Change From Baseline in Modified Rodnan Skin Score Over Time

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End point title

Change From Baseline in Modified Rodnan Skin Score Over Time

End point description

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. "99999" indicates values that could not be calculated.

End point type

Secondary

End point timeframe

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

End point values	Placebo	Pomalidomide
Number of subjects analysed	11 ^[11]	10 ^[12]
Units: unit's on a scale
arithmetic mean (standard deviation)
Week 12 (n = 10, 8)	-1.8 ± 3.94	-0.3 ± 1.83
Week 24 (n = 10, 8)	-3.6 ± 5.68	-2.0 ± 3.38
Week 64 (n = 6, 2)	-4.3 ± 8.36	-4.0 ± 2.83
Week 76 (n = 2, 1)	-8.5 ± 7.78	-7.0 ± 99999
Week 156/Early Termination (n = 6, 2)	-3.7 ± 8.52	-4.5 ± 3.54

Notes
[11] - FAS participants with a Baseline value and a post-baseline value at each time point.
[12] - FAS participants with a Baseline value and a post-baseline value at each time point.

No statistical analyses for this end point

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

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End point title

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

End point description

End point type

Secondary

End point timeframe

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

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[13]	10 ^[14]
Units: units on a scale
arithmetic mean (standard deviation)
Week 12 (n = 10, 8)	0.2 ± 0.36	-0.1 ± 0.30
Week 24 (n = 10, 8)	0.1 ± 0.23	-0.1 ± 0.20
Week 64 (n = 6, 2)	0.0 ± 0.20	0.4 ± 0.01
Week 76 (n = 2, 1)	-0.1 ± 0.01	0.5 ± 99999
Week 156/Early Termination (n = 6, 2)	0.0 ± 0.14	0.0 ± 0.14

Notes
[13] - FAS participants with a Baseline value and post-baseline value at each time point.
[14] - FAS participants with a Baseline value and post-baseline value at each time point.

No statistical analyses for this end point

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

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End point title

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

End point description

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. "99999" indicates values that could not be calculated.

End point type

Secondary

End point timeframe

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).

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[15]	10 ^[16]
Units: units on a scale
arithmetic mean (standard deviation)
Week 12 (n = 10, 8)	0.1 ± 0.36	-0.1 ± 0.51
Week 24 (n = 10, 8)	-0.1 ± 0.27	0.0 ± 0.47
Week 52/Early Termination (n = 12, 10)	-0.1 ± 0.54	0.1 ± 0.38
Week 64 (n = 6, 2)	-0.2 ± 0.14	0.2 ± 0.46
Week 76 (n = 2, 1)	-0.5 ± 0.18	-0.2 ± 99999
Week 156/Early Termination (n = 6, 2)	0.0 ± 0.44	0.1 ± 0.28

Notes
[15] - FAS participants with a Baseline value and post-baseline value at each time point.
[16] - FAS participants with a Baseline value and post-baseline value at each time point.

No statistical analyses for this end point

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

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End point title

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

End point description

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. "99999" indicates values that could not be calculated.

End point type

Secondary

End point timeframe

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).

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[17]	10 ^[18]
Units: units on a scale
arithmetic mean (standard deviation)
Week 12 (n = 10, 8)	0.4 ± 0.56	0.2 ± 1.21
Week 24 (n = 10, 8)	0.0 ± 0.53	0.3 ± 0.80
Week 52/Early Termination (n = 12, 10)	0.0 ± 0.55	0.2 ± 1.07
Week 64 (n = 6, 2)	-0.2 ± 0.70	1.0 ± 1.41
Week 76 (n = 2, 1)	0.0 ± 0.00	3.0 ± 99999
Week 156/Early Termination (n = 6, 2)	-0.3 ± 0.30	0.9 ± 1.24

Notes
[17] - FAS participants with a Baseline value and post-baseline value at each time point.
[18] - FAS participants with a Baseline value and post-baseline value at each time point.

No statistical analyses for this end point

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time

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End point title

Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time

End point description

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. "99999" indicates values that could not be calculated.

End point type

Secondary

End point timeframe

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).

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[19]	10 ^[20]
Units: units on a scale
arithmetic mean (standard deviation)
Week 12 (n = 10, 8)	0.0 ± 0.00	0.0 ± 0.00
Week 24 (n = 10, 8)	0.2 ± 0.42	0.0 ± 0.00
Week 52/Early Termination (n = 12, 9)	0.0 ± 0.00	0.1 ± 0.33
Week 64 (n = 6, 2)	0.2 ± 0.41	0.0 ± 0.00
Week 76 (n = 2, 1)	0.0 ± 0.00	0.0 ± 99999
Week 156/Early Termination (n = 6, 2)	0.2 ± 0.41	0.0 ± 0.00

Notes
[19] - FAS participants with a Baseline value and post-baseline value at each time point.
[20] - FAS participants with a Baseline value and post-baseline value at each time point.

No statistical analyses for this end point

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time

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End point title

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

End point description

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. "99999" indicates values that could not be calculated.

End point type

Secondary

End point timeframe

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).

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[21]	10 ^[22]
Units: units on a scale
arithmetic mean (standard deviation)
Week 12 (n = 10, 8)	0.4 ± 0.57	-0.2 ± 0.65
Week 24 (n = 10, 8)	0.1 ± 0.21	-0.3 ± 0.46
Week 52/Early Termination (n = 12, 10)	0.3 ± 0.34	0.0 ± 0.75
Week 64 (n = 6, 2)	0.1 ± 0.38	0.5 ± 0.71
Week 76 (n = 2, 1)	0.0 ± 0.00	-0.5 ± 99999
Week 156/Early Termination (n = 6, 2)	0.3 ± 0.42	-0.8 ± 0.35

Notes
[21] - FAS participants with a Baseline value and post-baseline value at each time point.
[22] - FAS participants with a Baseline value and post-baseline value at each time point.

No statistical analyses for this end point

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time

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End point title

Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time

End point description

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. "99999" indicates values that could not be calculated.

End point type

Secondary

End point timeframe

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).

End point values	Placebo	Pomalidomide
Number of subjects analysed	11 ^[23]	10 ^[24]
Units: unites on a scale
arithmetic mean (standard deviation)
Week 12 (n = 9, 8)	0.3 ± 0.49	0.0 ± 0.28
Week 24 (n = 9, 8)	0.1 ± 0.30	-0.1 ± 0.20
Week 52/Early Termination (n = 11, 10)	0.0 ± 0.25	0.2 ± 0.45
Week 64 (n = 5, 2)	0.0 ± 0.18	0.3 ± 0.35
Week 76 (n = 1, 1)	0.2 ± 99999	0.0 ± 99999
Week 156/Early Termination (n = 5, 2)	0.0 ± 0.25	-0.2 ± 0.23

Notes
[23] - FAS participants with a Baseline value and post-baseline value at each time point.
[24] - FAS participants with a Baseline value and post-baseline value at each time point.

No statistical analyses for this end point

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time

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End point title

Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time

End point description

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. "99999" indicates values that could not be calculated.

End point type

Secondary

End point timeframe

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).

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[25]	10 ^[26]
Units: units on a scale
arithmetic mean (standard deviation)
Week 12 (n = 10, 8)	0.2 ± 0.40	-0.4 ± 0.80
Week 24 (n = 10, 8)	0.1 ± 0.16	-0.3 ± 0.56
Week 52/Early Termination (n = 12, 10)	0.1 ± 0.25	-0.1 ± 0.42
Week 64 (n = 6, 2)	0.0 ± 0.36	0.2 ± 0.00
Week 76 (n = 2, 1)	0.0 ± 0.00	0.3 ± 99999
Week 156/Early Termination (n = 6, 2)	-0.1 ± 0.15	0.0 ± 0.00

Notes
[25] - FAS participants with a Baseline value and post-baseline value at each time point.
[26] - FAS participants with a Baseline value and post-baseline value at each time point.

No statistical analyses for this end point

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Constipation Subscale Score Over Time

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End point title

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

End point description

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. "99999" indicates values that could not be calculated.

End point type

Secondary

End point timeframe

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).

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[27]	10 ^[28]
Units: units on a scale
arithmetic mean (standard deviation)
Week 12 (n = 10, 8)	-0.1 ± 0.36	0.2 ± 0.98
Week 24 (n = 10, 8)	-0.2 ± 0.31	0.3 ± 0.81
Week 52/Early Termination (n = 12, 10)	0.0 ± 0.25	0.3 ± 0.51
Week 64 (n = 6, 2)	0.0 ± 0.60	0.1 ± 0.18
Week 76 (n = 2, 1)	0.0 ± 0.00	0.0 ± 99999
Week 156/Early Termination (n = 6, 2)	-0.2 ± 0.20	0.1 ± 0.18

Notes
[27] - FAS participants with a Baseline value and post-baseline value at each time point.
[28] - FAS participants with a Baseline value and post-baseline value at each time point.

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 12

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End point title

Change From Baseline in Dyspnea Functional Impairment at Week 12

End point description

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.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	Pomalidomide
Number of subjects analysed	10 ^[29]	7 ^[30]
Units: participants
Major deterioration	0	0
Moderate deterioration	1	1
Minor deterioration	0	1
No change	7	3
Minor improvement	2	1
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	1

Notes
[29] - FAS participants with available data
[30] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 24

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End point title

Change From Baseline in Dyspnea Functional Impairment at Week 24

End point description

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Pomalidomide
Number of subjects analysed	10 ^[31]	7 ^[32]
Units: participants
Major deterioration	1	0
Moderate deterioration	0	2
Minor deterioration	1	1
No change	4	2
Minor improvement	3	1
Moderate improvement	1	0
Major improvement	0	0
Further impairment for other reasons	0	1

Notes
[31] - FAS participants with available data
[32] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination

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End point title

Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination

End point description

End point type

Secondary

End point timeframe

Week 52 or at the Treatment Phase Early Termination visit

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[33]	10 ^[34]
Units: participants
Major deterioration	0	0
Moderate deterioration	0	4
Minor deterioration	1	1
No change	8	4
Minor improvement	3	1
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[33] - FAS participants with available data
[34] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 64

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End point title

Change From Baseline in Dyspnea Functional Impairment at Week 64

End point description

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	Pomalidomide
Number of subjects analysed	6 ^[35]	2 ^[36]
Units: participants
Major deterioration	0	1
Moderate deterioration	0	1
Minor deterioration	1	0
No change	4	0
Minor improvement	1	0
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[35] - FAS participants with available data
[36] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 76

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End point title

Change From Baseline in Dyspnea Functional Impairment at Week 76

End point description

End point type

Secondary

End point timeframe

Week 76

End point values	Placebo	Pomalidomide
Number of subjects analysed	2 ^[37]	1 ^[38]
Units: participants
Major deterioration	0	0
Moderate deterioration	0	1
Minor deterioration	1	0
No change	0	0
Minor improvement	1	0
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[37] - FAS participants with available data
[38] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination

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End point title

Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination

End point description

End point type

Secondary

End point timeframe

Week 156 or the Extension Phase Early Termination visit

End point values	Placebo	Pomalidomide
Number of subjects analysed	6 ^[39]	2 ^[40]
Units: participants
Major deterioration	0	0
Moderate deterioration	0	1
Minor deterioration	2	1
No change	2	0
Minor improvement	1	0
Moderate improvement	1	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[39] - FAS participants with available data
[40] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 12

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End point title

Change From Baseline in Dyspnea Magnitude of Task at Week 12

End point description

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.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	Pomalidomide
Number of subjects analysed	10 ^[41]	7 ^[42]
Units: participants
Major deterioration	0	0
Moderate deterioration	0	0
Minor deterioration	2	1
No change	5	5
Minor improvement	3	1
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[41] - FAS participants with available data
[42] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 24

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End point title

Change From Baseline in Dyspnea Magnitude of Task at Week 24

End point description

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.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Pomalidomide
Number of subjects analysed	10 ^[43]	7 ^[44]
Units: participants
Major deterioration	0	0
Moderate deterioration	1	1
Minor deterioration	2	1
No change	5	2
Minor improvement	2	3
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[43] - FAS participants with available data
[44] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination

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End point title

Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination

End point description

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.

End point type

Secondary

End point timeframe

Week 52 or at the Treatment Phase Early Termination visit

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[45]	10 ^[46]
Units: participants
Major deterioration	0	0
Moderate deterioration	0	3
Minor deterioration	1	1
No change	8	6
Minor improvement	2	0
Moderate improvement	0	0
Major improvement	1	0
Further impairment for other reasons	0	0

Notes
[45] - FAS participants with available data
[46] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 64

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End point title

Change From Baseline in Dyspnea Magnitude of Task at Week 64

End point description

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.

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	Pomalidomide
Number of subjects analysed	6 ^[47]	2 ^[48]
Units: participants
Major deterioration	0	1
Moderate deterioration	0	0
Minor deterioration	2	0
No change	3	0
Minor improvement	1	1
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[47] - FAS participants with available data
[48] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 76

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End point title

Change From Baseline in Dyspnea Magnitude of Task at Week 76

End point description

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.

End point type

Secondary

End point timeframe

Week 76

End point values	Placebo	Pomalidomide
Number of subjects analysed	2 ^[49]	1 ^[50]
Units: participants
Major deterioration	0	0
Moderate deterioration	0	0
Minor deterioration	1	0
No change	1	0
Minor improvement	0	1
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[49] - FAS participants with available data
[50] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination

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End point title

Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination

End point description

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.

End point type

Secondary

End point timeframe

Week 156 or the Extension Phase Early Termination visit

End point values	Placebo	Pomalidomide
Number of subjects analysed	6 ^[51]	2 ^[52]
Units: participants
Major deterioration	0	0
Moderate deterioration	1	0
Minor deterioration	1	1
No change	2	0
Minor improvement	2	1
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[51] - FAS participants with available data
[52] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 12

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End point title

Change From Baseline in Dyspnea Magnitude of Effort at Week 12

End point description

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.

End point type

Secondary

End point timeframe

Week 12

End point values	Placebo	Pomalidomide
Number of subjects analysed	10 ^[53]	7 ^[54]
Units: participants
Major deterioration	0	0
Moderate deterioration	1	0
Minor deterioration	2	2
No change	4	4
Minor improvement	2	1
Moderate improvement	1	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[53] - FAS participants with available data
[54] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 24

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End point title

Change From Baseline in Dyspnea Magnitude of Effort at Week 24

End point description

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.

End point type

Secondary

End point timeframe

Week 24

End point values	Placebo	Pomalidomide
Number of subjects analysed	10 ^[55]	7 ^[56]
Units: participants
Major deterioration	1	1
Moderate deterioration	0	1
Minor deterioration	1	0
No change	4	3
Minor improvement	3	2
Moderate improvement	1	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[55] - FAS participants with available data
[56] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination

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End point title

Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination

End point description

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.

End point type

Secondary

End point timeframe

Week 52 or at the Treatment Phase Early Termination visit

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[57]	10 ^[58]
Units: participants
Major deterioration	0	0
Moderate deterioration	0	3
Minor deterioration	1	1
No change	7	6
Minor improvement	3	0
Moderate improvement	1	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[57] - FAS participants with available data
[58] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 64

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End point title

Change From Baseline in Dyspnea Magnitude of Effort at Week 64

End point description

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.

End point type

Secondary

End point timeframe

Week 64

End point values	Placebo	Pomalidomide
Number of subjects analysed	6 ^[59]	2 ^[60]
Units: participants
Major deterioration	0	1
Moderate deterioration	0	0
Minor deterioration	3	0
No change	2	1
Minor improvement	1	0
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[59] - FAS participants with available data
[60] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 76

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End point title

Change From Baseline in Dyspnea Magnitude of Effort at Week 76

End point description

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.

End point type

Secondary

End point timeframe

Week 76

End point values	Placebo	Pomalidomide
Number of subjects analysed	2 ^[61]	1 ^[62]
Units: participants
Major deterioration	0	0
Moderate deterioration	0	0
Minor deterioration	1	0
No change	0	1
Minor improvement	1	0
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[61] - FAS participants with available data
[62] - FAS participants with available data

No statistical analyses for this end point

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination

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End point title

Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination

End point description

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.

End point type

Secondary

End point timeframe

Week 156 or at the Extension Phase Early Termination visit

End point values	Placebo	Pomalidomide
Number of subjects analysed	6 ^[63]	2 ^[64]
Units: participants
Major deterioration	0	0
Moderate deterioration	1	0
Minor deterioration	2	1
No change	2	1
Minor improvement	1	0
Moderate improvement	0	0
Major improvement	0	0
Further impairment for other reasons	0	0

Notes
[63] - FAS participants with available data
[64] - FAS participants with available data

No statistical analyses for this end point

Secondary: Oxygen Saturation Over Time

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End point title

Oxygen Saturation Over Time

End point description

Oxygen saturation was measured by pulse oximetry. "99999" indicates values that could not be calculated.

End point type

Secondary

End point timeframe

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).

End point values	Placebo	Pomalidomide
Number of subjects analysed	12 ^[65]	9 ^[66]
Units: percent saturation
arithmetic mean (standard deviation)
Baseline (n = 12, 9)	97.5 ± 2.07	96.8 ± 1.92
Week 12 (n = 10, 8)	97.1 ± 2.18	97.4 ± 1.51
Week 24 (n = 10, 8)	97.6 ± 1.65	96.5 ± 4.31
Week 52/Early Termination (n = 12, 9)	96.8 ± 2.18	96.8 ± 1.86
Week 64 (n = 6, 2)	96.3 ± 2.94	94.0 ± 2.83
Week 76 (n = 2, 1)	98.5 ± 0.71	97.0 ± 99999
Week 156/Early Termination (n = 6, 2)	95.8 ± 5.12	97.5 ± 0.71

Notes
[65] - FAS participants with a value at each time point.
[66] - FAS participants with a value at each time point.

No statistical analyses for this end point

Secondary: Pharmacokinetic Parameters of Pomalidomide in Plasma

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End point title

Pharmacokinetic Parameters of Pomalidomide in Plasma

End point description

Pharmacokinetic analyses were not conducted as there were too few participants with available data.

End point type

Secondary

End point timeframe

Day 1 and week 4 pre-dose and up to 24 hours post-dose.

End point values	Placebo	Pomalidomide
Number of subjects analysed	0 ^[67]	0 ^[68]
Units: ng/mL
arithmetic mean (standard deviation)	±	±

Notes
[67] - Pharmacokinetic analyses were not conducted as there were too few participants with available data
[68] - Pharmacokinetic analyses were not conducted as there were too few participants with available data

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

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.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

15.1

Reporting group title

Treatment Phase: Placebo

Reporting group description

Participants received placebo orally once a day for 52 weeks during the treatment phase.

Reporting group title

Treatment Phase: Pomalidomide

Reporting group description

Participants received 1 mg pomalidomide orally once a day for 52 weeks during the treatment phase.

Reporting group title

Extension Phase: Placebo/Pomalidomide

Reporting group description

In the open-label extension phase participants received 1 mg pomalidomide orally once a day for up to 2 years.

Reporting group title

Extension Phase: Pomalidomide/Pomalidomide

Reporting group description

Participants received 1 mg pomalidomide orally once a day for up to 2 years during the open-label extension phase.

Serious adverse events	Treatment Phase: Placebo	Treatment Phase: Pomalidomide	Extension Phase: Placebo/Pomalidomide	Extension Phase: Pomalidomide/Pomalidomide
Total subjects affected by serious adverse events
subjects affected / exposed	1 / 12 (8.33%)	4 / 10 (40.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
number of deaths (all causes)	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Chronic respiratory failure
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary embolism
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	1 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Pulmonary hypertension
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Renal and urinary disorders
Renal failure
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Pneumonia
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Sepsis
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Treatment Phase: Placebo	Treatment Phase: Pomalidomide	Extension Phase: Placebo/Pomalidomide	Extension Phase: Pomalidomide/Pomalidomide
Total subjects affected by non serious adverse events
subjects affected / exposed	12 / 12 (100.00%)	9 / 10 (90.00%)	5 / 6 (83.33%)	2 / 2 (100.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Vascular disorders
Hot flush
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	1	0	1	0
Hypertension
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Raynaud's phenomenon
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
General disorders and administration site conditions
Chills
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Device breakage
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Influenza like illness
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Non-cardiac chest pain
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Oedema
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	1	0	0	1
Oedema peripheral
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	2	0	0
Pyrexia
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	1	1	0
Pain
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	1	1	0	1
Immune system disorders
Contrast media allergy
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Seasonal allergy
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Social circumstances
Menopause
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Reproductive system and breast disorders
Amenorrhoea
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	1	0	1	0
Nipple pain
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Ovarian cyst ruptured
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	1	1	1	0
Dysphonia
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Dyspnoea
subjects affected / exposed	2 / 12 (16.67%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	2	0	0	1
Oropharyngeal pain
subjects affected / exposed	2 / 12 (16.67%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	2	0	1	0
Productive cough
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)
occurrences all number	0	0	2	0
Pulmonary hypertension
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	1 / 6 (16.67%)	1 / 2 (50.00%)
occurrences all number	1	0	1	2
Rhinorrhoea
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Sinus congestion
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Psychiatric disorders
Anxiety
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Depressed mood
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Insomnia
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	1	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Aspartate aminotransferase increased
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Blood creatinine increased
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Blood iron decreased
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Blood lactate dehydrogenase increased
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
C-reactive protein increased
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	1	0	0
Heart rate increased
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Hepatic enzyme increased
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
White blood cell count increased
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Injury, poisoning and procedural complications
Contusion
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Fall
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Ligament sprain
subjects affected / exposed	0 / 12 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Procedural pain
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Cardiac disorders
Palpitations
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Nervous system disorders
Ageusia
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Dizziness
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	1	0	0	1
Headache
subjects affected / exposed	3 / 12 (25.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	3	1	0	0
Hypoaesthesia
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	1	0	0
Migraine
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	1	0	0
Splenomegaly
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Ear and labyrinth disorders
Tinnitus
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Eye disorders
Conjunctivitis
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Gastrointestinal disorders
Abdominal pain upper
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Barrett's oesophagus
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Colonic polyp
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Constipation
subjects affected / exposed	1 / 12 (8.33%)	3 / 10 (30.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	3	0	0
Diarrhoea
subjects affected / exposed	3 / 12 (25.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	5	1	0	0
Dry mouth
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	1	0	0
Dyspepsia
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Gastric polyps
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Gastrooesophageal reflux disease
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	1	0	1
Hiatus hernia
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Mucous stools
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Mouth ulceration
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Nausea
subjects affected / exposed	2 / 12 (16.67%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	2	0	0	0
Hepatobiliary disorders
Biliary colic
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Cholecystitis
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Cholelithiasis
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Hepatic steatosis
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Skin and subcutaneous tissue disorders
Alopecia
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Butterfly rash
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Dermatitis acneiform
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Digital ulcer
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Dry skin
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	1	0	1	0
Eczema
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Hyperhidrosis
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Hyperkeratosis
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Macule
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Night sweats
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Papule
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Rash
subjects affected / exposed	1 / 12 (8.33%)	2 / 10 (20.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	2	0	0
Rash maculo-papular
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Rash papular
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Rash pruritic
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Rosacea
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Seborrhoeic dermatitis
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Skin ulcer
subjects affected / exposed	2 / 12 (16.67%)	0 / 10 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)
occurrences all number	3	0	2	0
Toxic skin eruption
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Renal and urinary disorders
Dysuria
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Glycosuria
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Renal failure
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	4 / 12 (33.33%)	4 / 10 (40.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	4	5	0	0
Joint swelling
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Muscle spasms
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Musculoskeletal chest pain
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Myalgia
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	1	0	0
Pain in jaw
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	0	1
Synovitis
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Tendon disorder
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Tendon pain
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Infections and infestations
Bronchitis
subjects affected / exposed	0 / 12 (0.00%)	2 / 10 (20.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Diverticulitis
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Folliculitis
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Gastroenteritis
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Infected skin ulcer
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Influenza
subjects affected / exposed	2 / 12 (16.67%)	0 / 10 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)
occurrences all number	2	0	2	0
Laryngitis viral
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	1	0	0
Localised infection
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Lower respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0
Tooth abscess
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Upper respiratory tract infection
subjects affected / exposed	3 / 12 (25.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	3	2	0	0
Urinary tract infection
subjects affected / exposed	2 / 12 (16.67%)	0 / 10 (0.00%)	2 / 6 (33.33%)	0 / 2 (0.00%)
occurrences all number	2	0	2	0
Viral upper respiratory tract infection
subjects affected / exposed	0 / 12 (0.00%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	0	2	0	0
Metabolism and nutrition disorders
Hyperglycaemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	0	1
Hypomagnesaemia
subjects affected / exposed	1 / 12 (8.33%)	1 / 10 (10.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	1	0	0
Hypophosphataemia
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	0 / 6 (0.00%)	1 / 2 (50.00%)
occurrences all number	0	0	0	1
Iron deficiency
subjects affected / exposed	1 / 12 (8.33%)	0 / 10 (0.00%)	0 / 6 (0.00%)	0 / 2 (0.00%)
occurrences all number	1	0	0	0
Vitamin D deficiency
subjects affected / exposed	0 / 12 (0.00%)	0 / 10 (0.00%)	1 / 6 (16.67%)	0 / 2 (0.00%)
occurrences all number	0	0	1	0

More information

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Were there any global substantial amendments to the protocol? Yes

08 Nov 2011

Significant changes included in this amendment are summarized below: - Increase the daily dose of pomalidomide from 0.5 mg to 1 mg. The amendment also included several other minor clarifications and corrections: - Deletion of calculated creatinine clearance as a serum chemistry assessment performed by the central lab. - Clarification of requirement to take study drug at the investigative site on the days of study visits. - Update of Figure 1 – “Overall Study Design” to reflect new dosage information. - Update of UCLA SCTC GIT 2.0 instrument (Appendix D) and SHAQ (Appendix E) scales.

20 Mar 2012

Significant changes included in this amendment are summarized below: - Clarification of the duration of the Long-term Follow-up Phase. - Deletion of DLco as an efficacy assessment and secondary endpoint. - Specification of required timeframes for discontinuation of short- and long-acting beta agonists and inhaled steroids prior to spirometry testing. - Inclusion of the definition of true abstinence. - Increase of heart rate entry exclusion criteria from < 45 beats per minute to < 50 beats per minute. - Modification of FEV1/FVC ratio definition of obstructive lung disease. - Lower threshold of heart rate-related stopping rule increased from < 40 beats per minute to < 45 beats per minute based on modification to protocol entrance criteria. - Modification of wording related to renal inclusion criteria and stopping rule requirements from serum creatinine to the MDRD eGFR reported in mL/min. Other changes included in this amendment are summarized below: - Modification of protocol wording to provide clarity and consistency throughout the document. - Inclusion of wording indicating experimental treatments are acceptable during the Long-term Follow-up Phase. - Modification of the footnote wording on the Overall Study Design Figure to clarify length of time of Long-term Follow-up Phase and to note that experimental treatments are permissible during this phase of the study. - Inclusion of wording regarding acceptable timeframe for DLco assessment required for study entry. - Clarification of protocol language regarding FVC study entry criteria. - Revision of footnote language in the Table of Events to reflect the deletion of DLco as a required assessment (beyond Screening). - Clarification of the timing of the first Long-term Follow-up Phase visit. - Correction of the total number of study visits.

14 Dec 2012

Significant changes included: - Addition of SSc-related cough status as an exploratory endpoint, and a cough visual analogue scale as a new assessment. - Modification of the inclusion criteria to permit up to 50% of enrolled subjects to have lSSc (limited cutaneous form systemic sclerosis). - Deletion of specific references to dSSc. - Modification of onset of the first non-Raynaud’s manifestation of SSc from 5 years to within 7 years of Screening. - Expansion of pulmonary-related inclusion criteria. - Deletion of history of hypercoagulable state exclusion criteria. - Clarification of terminology regarding HRCT findings consistent with SSc-ILD. - Lower threshold of DLco decreased to 35%. - Clarification of hepatitis test results inclusion/exclusion. - Modification of the list of acceptable concomitant medications to include: - Endothelin-1 inhibitors and prostaglandin analogues for digital ulcers if taken for at least 28 days prior to Screening. - Use of anti-thrombotic/anti coagulant medications if a subject is hospitalized and use is in the best interest of the subject. - Continued use/addition of certain concomitant medications which may promote QT/QTc prolongation, if there is a positive risk/benefit ratio and ECGs are closely monitored. - Cough medications. - Deletion of the requirement that subjects must be on oral statins for hyperlipidemia for ≥ 84 days prior to Screening. - Modification of the list of excluded prior treatments to include: - Use of bosentan, ambrisentan, iloprost, trepostinil, epoprostenol, sildenafil, tadalafil for PAH within 28 days. - Deletion of misorprostol as an unacceptable concomitant medication. - Addition of medications generally accepted to have a risk of causing torsades de pointes - Change of required concomitant medication washout periods for: - Cytotoxic/immunosuppressive agents from 84 days to within 28 days of Screening. - Clarification of the definitions of l

27 Mar 2014

Significant changes included: - Specification of target enrollment completion date. - Addition of Open-Label Extension Phase with inclusion of relevant information (eg, study duration, objectives, endpoints, rationale, etc.). - Clarification of timing of the Long-term Follow-up Phase. Other less significant revisions included: - Clarification of the timing of entry into the Observation Phase. - Modification of timeframe for evaluation of exploratory QoL endpoints. - Clarification of concomitant medication use during the course of the study. - Clarification of timeframe for IDMC involvement and monitoring responsibilities following dissolution of the IDMC. - Inclusion of assessment of quantitative serum beta-HCG if warranted. - Treatment Phase safety endpoints updated to include SAEs. - Clarification of unblinding procedures. - Update of the last visit on the Treatment Phase Table of Events to include assessments for Investigational Product Dispensing and Urine Pregnancy Testing. - Clarification of pregnancy testing requirements for non-menstruating FCBP. - Correction of UCLA SCTC GIT 2.0 instrument scoring information. - Clarification of timing of ECGs in both phases. - Clarification of Exclusion 9 to indicate acceptability of subjects having Sjogren’s syndrome secondary to systemic sclerosis. - Clarification of Exclusions 17 & 19 to indicate that specified abnormalities must be present on 2 of 3 Screening/Baseline ECGs - Update of Exclusion 33 to include macitentan as a treatment for PAH. - Addition of information regarding assignment of subject numbers for rescreened subjects. - Clarification of the use of anti-thrombotic medications vs subject discontinuation requirements. - Clarification of wording related to FVC analyses - Modification of “end-of-trial” definition and timing of analyses - Clarification regarding interim analyses. - Clarification of time frame for reporting SAEs

23 Sep 2015

The significant change included in this amendment is: - Termination of the Long-term Follow-up Phase intended to monitor for the occurrence of primary malignancies. Another, less significant revision is: - Updated information for Medical Monitor.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: 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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Primary: Number of Participants With Treatment-emergent Adverse Events (TEAEs)

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

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

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

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

Primary: 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

Primary: 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

Secondary: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time

Secondary: Change From Baseline in Percent Predicted Forced Vital Capacity Over Time

Secondary: Change From Baseline in Modified Rodnan Skin Score Over Time

Secondary: Change From Baseline in Modified Rodnan Skin Score Over Time

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

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

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

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

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

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

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Fecal Soilage Subscale Score Over Time

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Diarrhea Subscale Score Over Time

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Social Functioning Subscale Score Over Time

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Emotional Well Being Subscale Score Over Time

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Constipation Subscale Score Over Time

Secondary: Change From Baseline in UCLA SCTC GIT 2.0 Constipation Subscale Score Over Time

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 12

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 12

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 24

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 24

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 52/Early Termination

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 64

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 64

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 76

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 76

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination

Secondary: Change From Baseline in Dyspnea Functional Impairment at Week 156/Early Termination

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 12

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 12

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 24

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 24

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 52/Early Termination

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 64

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 64

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 76

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 76

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination

Secondary: Change From Baseline in Dyspnea Magnitude of Task at Week 156/Early Termination

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 12

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 12

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 24

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 24

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 52/Early Termination

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 64

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 64

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 76

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 76

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination

Secondary: Change From Baseline in Dyspnea Magnitude of Effort at Week 156/Early Termination

Secondary: Oxygen Saturation Over Time

Secondary: Oxygen Saturation Over Time

Secondary: Pharmacokinetic Parameters of Pomalidomide in Plasma

Secondary: Pharmacokinetic Parameters of Pomalidomide in Plasma

Adverse events

Adverse events

Clinical Trial Results:
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