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An Efficacy and Safety Study of Palovarotene to Treat Preosseous Flare-ups in FOP Subjects

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02190747
Recruitment Status : Completed
First Posted : July 15, 2014
Results First Posted : June 24, 2020
Last Update Posted : July 30, 2020
Sponsor:
Information provided by (Responsible Party):
Ipsen ( Clementia Pharmaceuticals Inc. )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Condition Fibrodysplasia Ossificans Progressiva
Interventions Drug: Palovarotene
Drug: Placebo
Enrollment 40
Recruitment Details Eight subjects were randomized 3:1 to either palovarotene or placebo in Cohort 1; 8 additional subjects were randomized 3:1 in an interim period between Cohorts 1 and 2. In Cohort 2, 24 additional fibrodysplasia ossificans progressiva (FOP) subjects were randomized 3:3:2 across 2 weight-based regimens of palovarotene or placebo.
Pre-assignment Details The study included clinically diagnosed FOP subjects at least 6 years of age (Cohort 2) or 15 years of age and older (Cohort 1) with symptomatic onset of a flare-up within 7 days of treatment start and accessible for treatment and follow-up.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description Subjects received palovarotene 10 milligram (mg) orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm. Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm. Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Period Title: Overall Study
Started 21 9 10
Completed 21 9 10
Not Completed 0 0 0
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo Total
Hide Arm/Group Description Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm. Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm. Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm. Total of all reporting groups
Overall Number of Baseline Participants 21 9 10 40
Hide Baseline Analysis Population Description
The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 21 participants 9 participants 10 participants 40 participants
22.8  (10.3) 17.9  (8.6) 21.2  (13.7) 21.3  (10.8)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 9 participants 10 participants 40 participants
Children (2-11 years) 3 4 2 9
Adolescents (12-17 years) 5 0 4 9
Adults (18-64 years) 13 5 4 22
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 9 participants 10 participants 40 participants
Female 9 6 7 22
Male 12 3 3 18
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 9 participants 10 participants 40 participants
Hispanic or Latino 2 1 1 4
Not Hispanic or Latino 13 8 6 27
Unknown or Not Reported 6 0 3 9
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 21 participants 9 participants 10 participants 40 participants
White 12 7 6 25
Black or African American 1 1 0 2
Asian 0 0 1 1
Multiple 2 1 0 3
Not available 6 0 3 9
1.Primary Outcome
Title Percentage of Responders at Week 6
Hide Description A responder was defined as a subject with no or minimal new heterotopic ossification (HO) at flare-up site versus baseline as assessed by plain radiographs at Week 6. Minimal new HO is defined as new HO with an HO score <=3 in both anterior/posterior (AP) and lateral projections (or if one view is non-interpretable or non-evaluable, then remaining evaluable view is used). The HO score ranges from 0 to 6 where, 0 = no HO and 6 = single contiguous HO with longest dimension >2 diameters of reference normotopic bone in any projection. The highest HO score from the 2 projections was used. Results from Primary Read reviews are presented. The Primary Read process included a double-read radiology review paradigm with consensus adjudication. Radiography and CT scans were examined independently by scan type, flare-up region, and imaging time point in order to determine whether radiography would be sufficient to measure new HO formation. Only subjects with interpretable outcomes were evaluated.
Time Frame Baseline (Day 1) and Week 6 (Day 42)
Hide Outcome Measure Data
Hide Analysis Population Description
The Per Protocol (PP) population included all subjects who were eligible for full analysis set (FAS) population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or computed tomography (CT) at Week 6 sufficient to allow determination of HO at flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 9 9
Measure Type: Number
Unit of Measure: percentage of subjects
100 88.9 88.9
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palovarotene 10/5 mg, Palovarotene 5/2.5 mg, Placebo
Comments Cochran-Armitage test of trend (one-sided). The Cochran-Armitage test of trend assessed the overall trend of response across the dose groups (from the lowest dose [or placebo], to the highest dose).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1664
Comments [Not Specified]
Method Cochran-Armitage test of trend
Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Subjects With New HO at Weeks 6 and 12
Hide Description Low dose CT scan was used as a secondary imaging assessment of HO and was performed at the same time points as plain radiographs. The percentage of subjects with new HO (regardless of the amount of new HO) at the flare-up site as assessed by CT scan and/or plain radiographs at Weeks 6 and 12 were analysed. The results are from Global Read reviews. The holistic Global Read process allowed concurrent review of all modalities across all time points, and provided access to selected clinical data at the time of review.
Time Frame Weeks 6 and 12 (Day 84)
Hide Outcome Measure Data
Hide Analysis Population Description
The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 9 10
Measure Type: Number
Unit of Measure: percentage of subjects
Week 6 15.0 22.2 30.0
Week 12 15.0 44.4 40.0
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palovarotene 10/5 mg, Palovarotene 5/2.5 mg, Placebo
Comments Week 6: Cochran-Armitage test of trend (one-sided). The Cochran-Armitage test of trend assessed the overall trend of response across the dose groups (from the lowest dose [or placebo], to the highest dose).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2335
Comments [Not Specified]
Method Cochran-Armitage test of trend
Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Palovarotene 10/5 mg, Palovarotene 5/2.5 mg, Placebo
Comments Week 12: Cochran-Armitage test of trend (one-sided). The Cochran-Armitage test of trend assessed the overall trend of response across the dose groups (from the lowest dose [or placebo], to the highest dose).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0837
Comments [Not Specified]
Method Cochran-Armitage test of trend
Comments [Not Specified]
3.Secondary Outcome
Title Change From Baseline in Amount (Area) of New HO Formed at the Flare-up Site at Weeks 6 and 12
Hide Description Interpretation of plain radiographs document the amount (area) of HO on both the AP and lateral radiograph views. The area for each view was a sum of all the new HO at the flare-up location (and thus if there are multiple HO lesions, the area of each lesion was determined and then the total across all lesions were summed to obtain a total new HO). This total new HO sum was used in the analysis of the area of new HO. Results from Primary Read reviews are presented.
Time Frame Baseline, Weeks 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 9 10
Mean (Standard Deviation)
Unit of Measure: square millimeters (mm)
Week 6 Number Analyzed 20 participants 9 participants 9 participants
0.00  (0.000) 38.85  (116.542) 75.89  (176.744)
Week 12 Number Analyzed 20 participants 9 participants 9 participants
19.00  (84.955) 71.22  (213.650) 621.71  (1287.519)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palovarotene 10/5 mg, Placebo
Comments Week 6: Analysis of area of new HO
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6984
Comments [Not Specified]
Method Pairwise test
Comments [Not Specified]
Method of Estimation Estimation Parameter Least square (LS) mean
Estimated Value -86.35
Parameter Dispersion
Type: Standard Error of the Mean
Value: 220.570
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Palovarotene 5/2.5 mg, Placebo
Comments Week 6: Analysis of area of new HO
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8811
Comments [Not Specified]
Method Pairwise test
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -38.07
Parameter Dispersion
Type: Standard Error of the Mean
Value: 252.192
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Palovarotene 10/5 mg, Placebo
Comments Week 12: Analysis of area of new HO
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0017
Comments [Not Specified]
Method Pairwise test
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -764.38
Parameter Dispersion
Type: Standard Error of the Mean
Value: 220.570
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Palovarotene 5/2.5 mg, Placebo
Comments Week 12: Analysis of area of new HO
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0094
Comments [Not Specified]
Method Pairwise test
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -703.43
Parameter Dispersion
Type: Standard Error of the Mean
Value: 252.192
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Responders at Week 12
Hide Description A responder was defined as a subject with no or minimal new HO at the flare-up site versus baseline as assessed by plain radiographs at Week 12. Minimal new HO is defined as new HO with an HO score <=3 in both the AP and lateral projections (or if one view is non-interpretable or non-evaluable, then the remaining evaluable view is used). The HO score ranges from 0 to 6 where, 0 = no HO and 6 = single contiguous HO with longest dimension >2 diameters of the reference normotopic bone in any projection. The highest HO score from the 2 projections was used. Results from the Primary Read reviews are presented. The Primary Read process included a double-read radiology review paradigm with consensus adjudication. Radiography and CT scans were examined independently by scan type, flare-up region, and imaging time point in order to determine whether radiography would be sufficient to measure new HO formation.
Time Frame Baseline and Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
The PP population included all subjects who were eligible for FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site. Only subjects with interpretable outcomes were evaluated.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 9 9
Measure Type: Number
Unit of Measure: percentage of subjects
95.0 88.9 77.8
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Palovarotene 10/5 mg, Palovarotene 5/2.5 mg, Placebo
Comments Cochran-Armitage test of trend (one-sided). The Cochran-Armitage test of trend assessed the overall trend of response across the dose groups (from the lowest dose [or placebo], to the highest dose).
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1503
Comments [Not Specified]
Method Cochran-Armitage test of trend
Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Bone Specific Alkaline Phosphatase at Weeks 2, 4, 6 and 12
Hide Description Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. Bone specific alkaline phosphatase was analysed as a bone and cartilage biomarker.
Time Frame Baseline, Weeks 2, 4, 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Mean (Standard Deviation)
Unit of Measure: microgram per liter (mcg/L)
Week 2 Number Analyzed 15 participants 4 participants 6 participants
-1.33  (13.267) -3.18  (4.619) 12.02  (35.263)
Week 4 Number Analyzed 15 participants 7 participants 6 participants
-1.41  (8.328) 3.80  (12.072) 7.53  (10.208)
Week 6 Number Analyzed 17 participants 7 participants 7 participants
-2.53  (8.157) 0.74  (3.316) 6.23  (6.851)
Week 12 Number Analyzed 16 participants 7 participants 7 participants
2.49  (5.506) 0.89  (6.738) 10.00  (10.091)
6.Secondary Outcome
Title Change From Baseline in C-Reactive Protein at Weeks 2, 4, 6 and 12
Hide Description Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. C-reactive protein was analysed as a inflammation biomarker.
Time Frame Baseline, Weeks 2, 4, 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Mean (Standard Deviation)
Unit of Measure: mg/L
Week 2 Number Analyzed 13 participants 6 participants 5 participants
8.62  (28.085) 0.09  (2.370) -1.59  (1.909)
Week 4 Number Analyzed 15 participants 7 participants 5 participants
1.48  (4.924) 23.26  (38.311) 2.34  (3.704)
Week 6 Number Analyzed 15 participants 7 participants 6 participants
0.14  (3.419) 2.70  (7.984) 1.20  (1.319)
Week 12 Number Analyzed 15 participants 7 participants 6 participants
2.82  (11.762) 1.27  (1.789) -0.30  (2.951)
7.Secondary Outcome
Title Change From Baseline in C-Terminal Telopeptide at Weeks 2, 4, 6 and 12
Hide Description Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. C-terminal telopeptide was analysed as a bone and cartilage biomarker.
Time Frame Baseline, Weeks 2, 4, 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Mean (Standard Deviation)
Unit of Measure: mcg/L
Week 2 Number Analyzed 15 participants 5 participants 5 participants
-0.020  (0.290) 0.118  (0.359) 0.071  (0.342)
Week 4 Number Analyzed 16 participants 8 participants 6 participants
0.015  (0.337) 0.095  (0.380) 0.188  (0.219)
Week 6 Number Analyzed 19 participants 8 participants 8 participants
0.105  (0.304) 0.078  (0.293) 0.125  (0.351)
Week 12 Number Analyzed 18 participants 8 participants 7 participants
0.116  (0.241) 0.054  (0.285) 0.126  (0.197)
8.Secondary Outcome
Title Change From Baseline in Procollagen Type 1 N-Terminal Propeptide at Weeks 2, 4, 6 and 12
Hide Description Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. Procollagen type 1 N-terminal propeptide was analysed as a bone and cartilage biomarker.
Time Frame Baseline, Weeks 2, 4, 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Mean (Standard Deviation)
Unit of Measure: mcg/L
Week 2 Number Analyzed 14 participants 4 participants 5 participants
53.022  (72.091) 78.930  (113.443) 42.058  (77.358)
Week 4 Number Analyzed 15 participants 8 participants 6 participants
123.986  (207.513) 117.476  (169.238) 194.193  (318.920)
Week 6 Number Analyzed 18 participants 8 participants 6 participants
141.304  (206.163) 147.409  (246.219) 252.328  (389.359)
Week 12 Number Analyzed 17 participants 8 participants 6 participants
120.489  (211.565) 25.766  (233.860) 141.367  (213.926)
9.Secondary Outcome
Title Change From Baseline in Procollagen Type 1 C-Terminal Propeptide Biomarker at Weeks 2, 4, 6 and 12
Hide Description Blood and urine samples for analysis of cartilage, bone, angiogenesis, and inflammation biomarkers were collected. Procollagen type 1 C-terminal propeptide was analysed as a bone and cartilage biomarker.
Time Frame Baseline, Weeks 2, 4, 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Mean (Standard Deviation)
Unit of Measure: mcg/L
Week 2 Number Analyzed 15 participants 5 participants 6 participants
22.12  (61.976) 23.26  (11.585) 82.93  (109.010)
Week 4 Number Analyzed 15 participants 8 participants 7 participants
72.16  (98.697) 76.10  (110.041) 140.26  (155.036)
Week 6 Number Analyzed 18 participants 8 participants 8 participants
73.36  (130.437) 87.19  (96.451) 125.31  (110.389)
Week 12 Number Analyzed 17 participants 8 participants 7 participants
51.21  (82.901) 47.30  (112.113) 96.49  (92.215)
10.Secondary Outcome
Title Change From Baseline in Amount of Bone Formation (Volume) at Weeks 6 and 12
Hide Description Low dose CT scan were used as a secondary imaging assessment of HO, and was performed at the same time points as plain radiographs. Interpretation of the CT scan documented the amount (volume) and grade of HO. The independent reviewer scored HO lesions according to the following scale for HO on CT. Grade 1 = fluid attenuation without evidence of calcification at CT, Grade 2 = calcification of soft tissues without evidence of bone formation, Grade 3 = immature bone formation, and Grade 4 = mature bone with cortical differentiation. Volume of new HO was determined according to the following steps: (1) calculate volume of new HO compared to baseline for each reviewer/HO ID, (2) sum the volume of new HO across HO IDs for each reviewer, and (3) average the volume of new HO across reviewers. Results from Primary Read reviews are presented.
Time Frame Baseline, Weeks 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 9 10
Mean (Standard Deviation)
Unit of Measure: cubic mm
Week 6 Number Analyzed 19 participants 9 participants 10 participants
2820.53  (11078.233) 326.58  (979.733) 11459.42  (29759.691)
Week 12 Number Analyzed 17 participants 9 participants 10 participants
3857.95  (11860.978) 1184.99  (3188.020) 16181.64  (41643.976)
11.Secondary Outcome
Title Percentage of Subjects With Soft Tissue Swelling and Cartilage Formation Assessed by Magnetic Resonance Imaging (MRI) or Ultrasound (US) at Weeks 6 and 12
Hide Description The MRI was utilized to evaluate the presence of soft tissue swelling/edema (and volume of the swelling/edema) and presence of cartilage formation (yes or no). For subjects who could not have an MRI, US was used to assess edema severity for the sub-set of subjects enrolled after this opinion was introduced in a protocol amendment. Imaging film from MRI was assessed by two independent readers. When there was sufficient agreement between the independent readers on volume, both of the independent readings were used for analysis with the volume measurements averaged. When there was insufficient agreement between the independent readers, an adjudication reading was provided and used for analysis. The US was used for soft tissue swelling/edema but not cartilage formation. Percentage calculated as % = 100 x n/N' where N' is the number of subjects with interpretable outcomes. Results from Primary Read reviews are presented.
Time Frame Weeks 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Measure Type: Number
Unit of Measure: percentage of subjects
Soft tissue swelling: Week 6 Number Analyzed 16 participants 8 participants 9 participants
50.0 50.0 66.7
Soft tissue swelling: Week 12 Number Analyzed 15 participants 9 participants 9 participants
60.0 66.7 66.7
Cartilage formation: Week 6 Number Analyzed 13 participants 3 participants 4 participants
15.4 0.0 0.0
Cartilage formation: Week 12 Number Analyzed 12 participants 3 participants 5 participants
8.3 0.0 0.0
12.Secondary Outcome
Title Change From Baseline in Percent of Normal Arc of Motion at the Primary Joint (Flare-up Site) at Weeks 6 and 12
Hide Description Active range of motion, expressed as the percent of normal arc of motion, measurements at the primary joint associated with the flare-up and adjoining joints was assessed by goniometer.
Time Frame Baseline, Weeks 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Mean (Standard Deviation)
Unit of Measure: percent of normal arc of motion
Week 6 Number Analyzed 20 participants 8 participants 10 participants
-0.40  (9.574) -1.36  (21.336) -0.99  (18.951)
Week 12 Number Analyzed 20 participants 8 participants 10 participants
0.58  (15.079) -4.23  (26.791) -2.31  (18.963)
13.Secondary Outcome
Title Subject and Investigator Global Assessment of Movement at Weeks 6 and 12
Hide Description Flare-up movement outcomes were independently assessed by both the subject (or parent of a subject under 8 years of age) and the Investigator at Weeks 6 and 12 by completing the global assessment of movement. The subject/parent completed the global assessment first. Prior to reviewing the subject's assessment, the Investigator completed his/her own assessment of the flare-up outcome. Subjects were assessed how the flare-up affected their movement on a scale ranging 1 to 5 where, 1 = severely worse movement and 5 = better movement compared with study Day 1 (day of first dose of study drug). Investigators were assessed how the flare-up affected the subject's movement on a scale ranging 1 to 5 where, 1 = severely worse movement and 5 = better movement compared with baseline (day of screening physical examination).
Time Frame Weeks 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site. Only subjects with non-missing values were presented.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Measure Type: Count of Participants
Unit of Measure: Participants
Subject Global Assessment: Week 6 Number Analyzed 9 participants 8 participants 6 participants
Score 1 0 1 0
Score 2 1 0 0
Score 3 0 0 1
Score 4 2 3 2
Score 5 6 4 3
Subject Global Assessment: Week 12 Number Analyzed 13 participants 9 participants 7 participants
Score 1 0 1 0
Score 2 0 1 1
Score 3 1 0 1
Score 4 6 2 4
Score 5 6 5 1
Investigator Global Assessment: Week 6 Number Analyzed 9 participants 8 participants 6 participants
Score 1 1 1 0
Score 2 0 0 1
Score 3 0 0 1
Score 4 3 2 3
Score 5 5 5 1
Investigator Global Assessment: Week 12 Number Analyzed 13 participants 9 participants 7 participants
Score 1 1 1 1
Score 2 0 1 0
Score 3 0 1 0
Score 4 8 2 4
Score 5 4 4 2
14.Secondary Outcome
Title Change From Baseline in Flare-Up Pain and Swelling at Weeks 2, 4, 6, 9 and 12
Hide Description The pain and swelling associated with flare-ups was evaluated using 2 separate numeric rating scales, one for pain and one for swelling. The pain scale ranges from 0 to 10 where, 0 = no pain and 10 = worst pain ever experienced. The swelling scale ranges from 0 to 10 where, 0 = no swelling and 10 = worst swelling ever experienced. The Faces Pain Scale - Revised (FPS-R) was used for children less than 8 years old. The FPS-R ranges from 0 to 10 where, 0 = no pain and 10 = very much pain in two-point increments.
Time Frame Baseline, Weeks 2, 4, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 9 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Flare-up pain: Week 2 Number Analyzed 20 participants 9 participants 10 participants
-2.5  (2.50) 0.0  (2.40) -2.0  (1.76)
Flare-up pain: Week 4 Number Analyzed 20 participants 9 participants 10 participants
-3.2  (2.46) -1.3  (1.58) -1.9  (3.14)
Flare-up pain: Week 6 Number Analyzed 20 participants 9 participants 10 participants
-3.5  (2.78) -1.3  (1.58) -2.4  (2.91)
Flare-up pain: Week 9 Number Analyzed 19 participants 8 participants 10 participants
-3.8  (2.62) -1.1  (1.64) -2.1  (1.85)
Flare-up pain: Week 12 Number Analyzed 20 participants 9 participants 10 participants
-3.6  (2.72) -1.9  (2.42) -2.2  (2.53)
Flare-up swelling: Week 2 Number Analyzed 20 participants 7 participants 10 participants
-1.4  (2.76) -1.3  (2.93) -2.3  (2.79)
Flare-up swelling: Week 4 Number Analyzed 19 participants 8 participants 10 participants
-1.7  (3.30) -1.9  (1.81) -2.0  (3.30)
Flare-up swelling: Week 6 Number Analyzed 20 participants 8 participants 10 participants
-2.2  (3.32) -2.0  (2.45) -2.6  (3.50)
Flare-up swelling: Week 9 Number Analyzed 19 participants 7 participants 10 participants
-2.7  (3.32) -2.3  (2.43) -1.9  (4.41)
Flare-up swelling: Week 12 Number Analyzed 20 participants 8 participants 10 participants
-2.1  (3.73) -2.5  (2.20) -2.3  (3.16)
15.Secondary Outcome
Title Percentage of Subjects Who Used Any Assistive Devices and Adaptations for Daily Living at Weeks 6 and 12
Hide Description Subjects were given a list of FOP assistive devices and adaptations and asked to select those they use for daily living. The FOP assistive devices and adaptations included mobility aids, care attendants, eating tools, personal care tools/aids, bathroom aids and devices, bedroom aids and devices, home adaptations, work environment adaptations, technology adaptations, sports and recreation adaptations, school, and medical therapies for daily living.
Time Frame Weeks 6 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Measure Type: Number
Unit of Measure: percentage of subjects
Week 6 Number Analyzed 20 participants 9 participants 10 participants
85.0 100.0 100.0
Week 12 Number Analyzed 21 participants 9 participants 10 participants
90.5 100.0 100.0
16.Secondary Outcome
Title Duration of Active Symptomatic Flare-up
Hide Description The duration of active symptomatic flare-up was defined as the number of days the subject reported the presence of symptoms in the diary ('Is your flare-up ongoing today?') from Day 1 to study completion at Day 84. The mean number of days of active, symptomatic flare-up is presented for subjects with evaluable diary data.
Time Frame From Day 1 to Day 84
Hide Outcome Measure Data
Hide Analysis Population Description
The PP population included all subjects who were eligible for the FAS population, completed Week 6 study visit with no major protocol deviations with at least 80% compliance with study drug, and had an evaluable radiograph or CT at Week 6 sufficient to allow determination of HO at flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 17 9 8
Mean (Standard Deviation)
Unit of Measure: days
22.1  (20.53) 44.1  (38.36) 34.4  (34.15)
17.Secondary Outcome
Title Change From Baseline in Percentage of Worst Total Score for FOP-Specific Physical Function Questionnaire (FOP-PFQ) at Weeks 2, 4, 6, 9 and 12
Hide Description The FOP-PFQ consists of 28 questions rated on scales from 1 to 5, with lower scores denoting more difficulty. The adult form of the FOP-PFQ was administered to subjects 15 years of age and older. There are two Pediatric FOP-PFQ (FOP-PFQ-P) forms: a self-completed form for 8 to 14 year-olds and a parent proxy-completed form for 5 to 14 year-olds. For subjects between 8 to 14 years of age, both the self-completed (for 8 to 14 year-olds) and the proxy-completed (for 5 to 14 year olds) forms of the FOP-PFQ-P were administered. However, only the proxy-completed form was used for analysis. Percentage of worst scores ranges from 0% to 100% with 0% = best possible function and 100% = worst possible function. Change from baseline for each time point is presented.
Time Frame Baseline, Weeks 2, 4, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Mean (Standard Deviation)
Unit of Measure: units on a scale
Week 2 Number Analyzed 21 participants 9 participants 10 participants
0.95  (5.484) 0.31  (3.818) 2.11  (6.659)
Week 4 Number Analyzed 20 participants 9 participants 10 participants
3.42  (7.932) 2.67  (7.200) 2.91  (8.427)
Week 6 Number Analyzed 21 participants 9 participants 9 participants
3.79  (7.787) 2.88  (7.550) 1.75  (5.980)
Week 9 Number Analyzed 19 participants 8 participants 10 participants
1.89  (5.432) -0.52  (7.881) 4.91  (13.185)
Week 12 Number Analyzed 20 participants 9 participants 10 participants
4.22  (7.915) 1.08  (8.724) 3.02  (9.587)
18.Secondary Outcome
Title Change From Baseline in Physical and Mental Health Using Age-Appropriate Forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Weeks 2, 4, 6, 9 and 12
Hide Description The PROMIS Global Health contains 10 questions which are rated on scales from 1 to 5 or 0 to 10. Global physical health scores were calculated as the sum of scores from parameters 3, 6, 7, and 8 and ranges from 4 to 20 where, 4 = worse health and 20 = better health. Global mental health scores were calculated as the sum of scores from parameters 2, 4, 5, and 10 and ranges from 4 to 20 where, 4 = worse health and 20 = better health. For paediatric subjects, the PROMIS was administered as per the adult version. However, there is a single total score for the paediatric PROMIS (as opposed to global physical and global mental health scores as are in the adult version). The total score were converted to a T-score. A T-score of 50 is normal and increments of 10 are +/- 1 standard deviation away from the norm. A T-score <50 indicates worse health, while a T-score >50 indicates better health. The higher values (positive changes) indicate better health.
Time Frame Baseline, Weeks 2, 4, 6, 9 and 12
Hide Outcome Measure Data
Hide Analysis Population Description
The FAS population included all subjects who received at least 1 dose of study drug and had at least 1 evaluable post-baseline radiograph or CT sufficient to allow determination of HO at the flare-up site.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 21 9 10
Mean (Standard Deviation)
Unit of Measure: t-score
Adult-only: Global Physical Health T-Score: Week 2 Number Analyzed 17 participants 5 participants 5 participants
2.76  (5.308) 0.00  (1.768) 5.90  (2.087)
Adult-only: Global Physical Health T-Score: Week 4 Number Analyzed 17 participants 5 participants 5 participants
4.66  (6.590) 2.66  (4.345) 5.56  (2.904)
Adult-only: Global Physical Health T-Score: Week 6 Number Analyzed 17 participants 5 participants 4 participants
4.69  (5.585) 7.08  (6.591) 5.73  (2.750)
Adult-only: Global Physical Health T-Score: Week 9 Number Analyzed 15 participants 4 participants 5 participants
4.96  (5.489) 5.58  (3.381) 4.94  (3.135)
Adult-only:Global Physical Health T-Score: Week 12 Number Analyzed 16 participants 5 participants 5 participants
3.97  (6.764) 4.98  (6.246) 3.78  (3.883)
Adult-only: Global Mental Health T-Score: Week 2 Number Analyzed 17 participants 5 participants 5 participants
3.66  (5.216) 3.20  (2.024) 1.98  (3.124)
Adult-only: Global Mental Health T-Score: Week 4 Number Analyzed 17 participants 5 participants 5 participants
3.32  (5.066) 2.28  (2.700) 7.30  (5.609)
Adult-only: Global Mental Health T-Score: Week 6 Number Analyzed 17 participants 5 participants 5 participants
4.15  (6.878) 2.54  (4.980) 4.34  (5.850)
Adult-only: Global Mental Health T-Score: Week 9 Number Analyzed 15 participants 4 participants 5 participants
4.62  (7.684) 1.68  (3.641) 5.38  (5.438)
Adult-only: Global Mental Health T-Score: Week 12 Number Analyzed 16 participants 5 participants 5 participants
4.33  (7.527) 3.10  (4.127) 1.04  (3.664)
Paediatric-only: Global Health T-Score: Week 2 Number Analyzed 3 participants 4 participants 3 participants
-2.27  (4.278) 1.05  (2.352) -1.80  (4.668)
Paediatric-only: Global Health T-Score: Week 4 Number Analyzed 3 participants 4 participants 3 participants
-0.57  (2.499) 1.43  (6.352) -6.40  (4.314)
Paediatric-only: Global Health T-Score: Week 6 Number Analyzed 3 participants 4 participants 3 participants
-2.23  (3.499) 2.80  (4.955) -3.30  (7.826)
Paediatric-only: Global Health T-Score: Week 9 Number Analyzed 3 participants 4 participants 3 participants
1.17  (2.021) 1.83  (1.434) -3.50  (4.668)
Paediatric-only: Global Health T-Score: Week 12 Number Analyzed 3 participants 4 participants 3 participants
0.17  (7.572) -2.13  (2.964) -6.57  (1.950)
19.Secondary Outcome
Title Maximum Measured Plasma Concentration (Cmax) of Palovarotene
Hide Description The Cmax of palovarotene was determined.
Time Frame Pre-dose and 3, 6, 10, and 24 hours (hrs) post-dose at Week 2, and at Week 4 or 6
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic (PK) population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 8
Mean (Standard Deviation)
Unit of Measure: picograms per milliliter (pg/mL)
Week 2 Number Analyzed 15 participants 5 participants
95620.00  (30296.77) 35620.00  (19882.08)
Week 4/Week 6 Number Analyzed 17 participants 7 participants
45505.88  (17061.05) 18958.57  (9238.62)
20.Secondary Outcome
Title Minimum Measured Plasma Concentration (Cmin) of Palovarotene
Hide Description The Cmin of palovarotene was determined.
Time Frame Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 8
Mean (Standard Deviation)
Unit of Measure: pg/mL
Week 2 Number Analyzed 15 participants 5 participants
3128.53  (2358.88) 1739.40  (963.68)
Week 4/Week 6 Number Analyzed 17 participants 7 participants
3879.00  (7042.29) 614.14  (289.72)
21.Secondary Outcome
Title Time of Maximum Measured Plasma Concentration (Tmax) of Palovarotene
Hide Description The Tmax obtained by inspection of palovarotene was determined.
Time Frame Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 8
Median (Full Range)
Unit of Measure: hr
Week 2 Number Analyzed 15 participants 5 participants
3.00
(2.83 to 6.03)
2.77
(2.08 to 5.88)
Week 4/Week 6 Number Analyzed 17 participants 7 participants
3.00
(2.75 to 6.00)
3.00
(3.00 to 6.00)
22.Secondary Outcome
Title Apparent Terminal Elimination Half-life (t1/2) of Palovarotene
Hide Description The t1/2 was calculated as ln(2)/ λz. The number of data points included in the regression was determined by visual inspection, but a minimum of three data points in the terminal phase, excluding Cmax, was required to estimate λz.
Time Frame Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 8
Median (Full Range)
Unit of Measure: hr
Week 2 Number Analyzed 11 participants 4 participants
4.33
(3.30 to 6.51)
5.18
(3.29 to 5.94)
Week 4/Week 6 Number Analyzed 16 participants 4 participants
4.39
(3.11 to 6.38)
4.40
(4.13 to 5.11)
23.Secondary Outcome
Title Area Under the Plasma Concentration Versus Time Curve Over the 24-hr Dosing Interval (AUC[0-24hr]) of Palovarotene
Hide Description The AUC(0-24hr) was calculated using linear trapezoid rule.
Time Frame Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 8
Mean (Standard Deviation)
Unit of Measure: hr*pg/mL
Week 2 Number Analyzed 13 participants 4 participants
686308.92  (246797.81) 350124.65  (181967.49)
Week 4/Week 6 Number Analyzed 17 participants 7 participants
311082.39  (128622.73) 142748.47  (84838.75)
24.Secondary Outcome
Title Apparent Clearance of Palovarotene (CL/F)
Hide Description The CL/F was defined as dose/AUC0-24hr.
Time Frame Pre-dose and 3, 6, 10, and 24 hrs post-dose at Week 2, and at Week 4 or 6
Hide Outcome Measure Data
Hide Analysis Population Description
The PK population included all subjects who had sufficient blood samples collected for valid estimation of PK parameters.
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg
Hide Arm/Group Description:
Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm.
Overall Number of Participants Analyzed 20 8
Mean (Standard Deviation)
Unit of Measure: L/hr
Week 2 Number Analyzed 13 participants 4 participants
15.55  (7.03) 12.84  (4.07)
Week 4/Week 6 Number Analyzed 17 participants 7 participants
17.71  (7.44) 19.51  (10.66)
Time Frame From first dose of study drug (Day 1) up to and including the Week 12 visit, approximately 85 days.
Adverse Event Reporting Description Treatment-emergent adverse events were those with a start date/time after the first dose of study medication. The safety population included all subjects who received at least 1 dose of study drug (placebo or palovarotene).
 
Arm/Group Title Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Hide Arm/Group Description Subjects received palovarotene 10 mg orally for 14 days followed by 5 mg orally for 28 days during flare-ups (10/5 mg regimen). The subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm. Subjects received palovarotene 5 mg orally for 14 days followed by 2.5 mg orally for 28 days during flare-ups (5/2.5 mg regimen). The subjects were followed for an additional 42 days without treatment. Only subjects in Cohort 2 contributed to this arm. Subjects received placebo (matching with palovarotene) for 42 days during flare-ups. Subjects were followed for an additional 42 days without treatment. Subjects in Cohort 1 and Cohort 2 contributed to this arm.
All-Cause Mortality
Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/21 (0.00%)      0/9 (0.00%)      0/10 (0.00%)    
Hide Serious Adverse Events
Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/21 (9.52%)      1/9 (11.11%)      1/10 (10.00%)    
General disorders       
Condition aggravated  1 [1]  2/21 (9.52%)  2 0/9 (0.00%)  0 0/10 (0.00%)  0
Nervous system disorders       
Myoclonus  1  1/21 (4.76%)  4 0/9 (0.00%)  0 0/10 (0.00%)  0
Reproductive system and breast disorders       
Haemorrhagic ovarian cyst  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Respiratory, thoracic and mediastinal disorders       
Asthmatic crisis  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
[1]
Any flare-ups reported during the 12-week duration of the study, which were not the flare-up that qualified the subject for the study, were recorded as adverse events.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Palovarotene 10/5 mg Palovarotene 5/2.5 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   21/21 (100.00%)      9/9 (100.00%)      10/10 (100.00%)    
Blood and lymphatic system disorders       
Leukocytosis  1  0/21 (0.00%)  0 1/9 (11.11%)  1 1/10 (10.00%)  1
Thrombocytopenia  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Iron deficiency anaemia  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Eye disorders       
Dry eye  1  1/21 (4.76%)  1 2/9 (22.22%)  2 0/10 (0.00%)  0
Eye pruritus  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Vision blurred  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Gastrointestinal disorders       
Lip dry  1  7/21 (33.33%)  8 5/9 (55.56%)  5 1/10 (10.00%)  1
Nausea  1  6/21 (28.57%)  7 1/9 (11.11%)  1 2/10 (20.00%)  2
Chapped lips  1  5/21 (23.81%)  6 0/9 (0.00%)  0 2/10 (20.00%)  2
Diarrhoea  1  4/21 (19.05%)  4 0/9 (0.00%)  0 1/10 (10.00%)  1
Dry mouth  1  3/21 (14.29%)  3 1/9 (11.11%)  1 0/10 (0.00%)  0
Abdominal pain  1  1/21 (4.76%)  1 1/9 (11.11%)  1 1/10 (10.00%)  1
Vomiting  1  1/21 (4.76%)  1 1/9 (11.11%)  1 2/10 (20.00%)  2
Constipation  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Flatulence  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Frequent bowel movements  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Abdominal pain upper  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
General disorders       
Condition aggravated  1 [1]  13/21 (61.90%)  27 2/9 (22.22%)  2 3/10 (30.00%)  3
Pyrexia  1  1/21 (4.76%)  2 3/9 (33.33%)  4 1/10 (10.00%)  1
Application site erythema  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Fatigue  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Feeling cold  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Vessel puncture site bruise  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Chest pain  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  2
Infections and infestations       
Upper respiratory tract infection  1  1/21 (4.76%)  1 2/9 (22.22%)  2 0/10 (0.00%)  0
Influenza  1  2/21 (9.52%)  2 0/9 (0.00%)  0 0/10 (0.00%)  0
Pharyngitis  1  1/21 (4.76%)  1 1/9 (11.11%)  1 0/10 (0.00%)  0
Nasopharyngitis  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Oral candidiasis  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Urinary tract infection  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Injury, poisoning and procedural complications       
Contusion  1  1/21 (4.76%)  1 1/9 (11.11%)  1 0/10 (0.00%)  0
Excoriation  1  2/21 (9.52%)  3 0/9 (0.00%)  0 0/10 (0.00%)  0
Post-traumatic pain  1  2/21 (9.52%)  4 0/9 (0.00%)  0 0/10 (0.00%)  0
Fall  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Investigations       
Haemoglobin decreased  1  1/21 (4.76%)  1 1/9 (11.11%)  1 0/10 (0.00%)  0
Lipase increased  1  2/21 (9.52%)  5 0/9 (0.00%)  0 1/10 (10.00%)  5
Blood alkaline phosphatase increased  1  1/21 (4.76%)  1 0/9 (0.00%)  0 1/10 (10.00%)  1
Blood bilirubin increased  1  1/21 (4.76%)  1 0/9 (0.00%)  0 1/10 (10.00%)  2
Blood thyroid stimulating hormone decreased  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Gamma-glutamyltransferase increased  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Amylase increased  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  3
Blood potassium increased  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Thyroxine free increased  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Thyroxine increased  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Metabolism and nutrition disorders       
Hypercholesterolaemia  1  1/21 (4.76%)  1 1/9 (11.11%)  1 0/10 (0.00%)  0
Increased appetite  1  1/21 (4.76%)  1 1/9 (11.11%)  1 0/10 (0.00%)  0
Hyperglycaemia  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Musculoskeletal and connective tissue disorders       
Arthralgia  1  10/21 (47.62%)  13 1/9 (11.11%)  4 6/10 (60.00%)  14
Pain in extremity  1  2/21 (9.52%)  2 3/9 (33.33%)  4 2/10 (20.00%)  3
Joint swelling  1  2/21 (9.52%)  2 1/9 (11.11%)  2 0/10 (0.00%)  0
Joint stiffness  1  2/21 (9.52%)  2 0/9 (0.00%)  0 0/10 (0.00%)  0
Musculoskeletal stiffness  1  2/21 (9.52%)  2 0/9 (0.00%)  0 0/10 (0.00%)  0
Neck pain  1  1/21 (4.76%)  1 1/9 (11.11%)  1 0/10 (0.00%)  0
Back pain  1  1/21 (4.76%)  1 0/9 (0.00%)  0 2/10 (20.00%)  2
Groin pain  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Bone pain  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Myalgia  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Muscle spasms  1  1/21 (4.76%)  3 0/9 (0.00%)  0 1/10 (10.00%)  1
Nervous system disorders       
Headache  1  8/21 (38.10%)  9 1/9 (11.11%)  1 3/10 (30.00%)  5
Dizziness  1  1/21 (4.76%)  2 1/9 (11.11%)  2 0/10 (0.00%)  0
Hypoaesthesia  1  0/21 (0.00%)  0 2/9 (22.22%)  3 2/10 (20.00%)  5
Migraine  1  1/21 (4.76%)  1 1/9 (11.11%)  1 0/10 (0.00%)  0
Psychiatric disorders       
Insomnia  1  2/21 (9.52%)  2 0/9 (0.00%)  0 0/10 (0.00%)  0
Irritability  1  2/21 (9.52%)  2 0/9 (0.00%)  0 0/10 (0.00%)  0
Renal and urinary disorders       
Pollakiuria  1  2/21 (9.52%)  3 2/9 (22.22%)  2 0/10 (0.00%)  0
Haematuria  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Polyuria  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Glycosuria  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Respiratory, thoracic and mediastinal disorders       
Cough  1  1/21 (4.76%)  1 1/9 (11.11%)  1 0/10 (0.00%)  0
Nasal congestion  1  1/21 (4.76%)  1 1/9 (11.11%)  1 0/10 (0.00%)  0
Epistaxis  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Rhinorrhoea  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Skin and subcutaneous tissue disorders       
Dry skin  1  17/21 (80.95%)  38 5/9 (55.56%)  5 3/10 (30.00%)  3
Erythema  1  3/21 (14.29%)  6 2/9 (22.22%)  2 0/10 (0.00%)  0
Pruritus generalised  1  4/21 (19.05%)  5 1/9 (11.11%)  1 0/10 (0.00%)  0
Dermatitis acneiform  1  4/21 (19.05%)  5 0/9 (0.00%)  0 0/10 (0.00%)  0
Pruritus  1  4/21 (19.05%)  5 0/9 (0.00%)  0 0/10 (0.00%)  0
Eczema  1  2/21 (9.52%)  3 1/9 (11.11%)  2 0/10 (0.00%)  0
Rash maculo-papular  1  2/21 (9.52%)  2 0/9 (0.00%)  0 0/10 (0.00%)  0
Skin exfoliation  1  2/21 (9.52%)  2 0/9 (0.00%)  0 0/10 (0.00%)  0
Dandruff  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Dermatitis contact  1  0/21 (0.00%)  0 1/9 (11.11%)  2 0/10 (0.00%)  0
Ecchymosis  1  0/21 (0.00%)  0 1/9 (11.11%)  1 0/10 (0.00%)  0
Rash  1  0/21 (0.00%)  0 1/9 (11.11%)  2 0/10 (0.00%)  0
Macule  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Pain of skin  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Skin hypopigmentation  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
Vascular disorders       
Pallor  1  0/21 (0.00%)  0 0/9 (0.00%)  0 1/10 (10.00%)  1
1
Term from vocabulary, MedDRA (17.0)
Indicates events were collected by systematic assessment
[1]
Any flare-ups reported during the 12-week duration of the study, which were not the flare-up that qualified the subject for the study, were recorded as adverse events.
Radiography was less sensitive than CT for detecting new HO. Thus, Global Read data are presented where available using more sensitive CT scans at Week 12 in the PP population.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Director
Organization: Ipsen
Phone: see email
EMail: clinical.trials@ipsen.com
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Responsible Party: Ipsen ( Clementia Pharmaceuticals Inc. )
ClinicalTrials.gov Identifier: NCT02190747    
Other Study ID Numbers: PVO-1A-201
2014-001453-17 ( EudraCT Number )
First Submitted: July 13, 2014
First Posted: July 15, 2014
Results First Submitted: June 3, 2020
Results First Posted: June 24, 2020
Last Update Posted: July 30, 2020