Trial Outcomes & Findings for An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP) (NCT NCT02279095)

Last Updated: 2025-02-19

Results Overview

A responder was defined as a participant with no or minimal new HO at original flare-up site compared with baseline (pre-dose data from PVO-1A-201 study). Minimal new HO was defined as new HO with an HO score \<=3 in both the anterior/posterior (AP) and lateral projections (or if 1 view is noninterpretable or non-evaluable, then remaining evaluable view was used). The HO score ranged 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. Highest HO score from 2 projections was used.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

58 participants

Primary outcome timeframe

Baseline and Week 12

Results posted on

2025-02-19

Participant Flow

This Phase 2, open-label extension of study PVO-1A-201 was conducted in participants with FOP at 8 investigational sites in 5 countries. Participants enrolled in France were followed under a country-specific study PVO-1A-204 (as Part B of the study) as requested by French regulatory authorities. Overall, 58 participants were enrolled in this study.

Study divided into 4 parts: Part A (participants who completed PVO-1A-201 study were enrolled and followed for 3 years), Part B (participants from Part A and 18 new adult participants were followed for 2 years), Part C (participants from Part B were followed for 2 years) and Part D (treatment discontinued participants were followed for 2 years).

Participant milestones

Participant milestones
Measure	All Participants Participants who completed PVO-1A-201 study were followed for up to 36 months in Part A. Eligible participants with a flare-up received palovarotene 10 milligram (mg) capsule orally daily for 2 weeks followed by 5 mg daily for 4 weeks during the flare-up component of Part A. In Part B, eligible participants from Part A and participants from the new Adult Cohort received chronic treatment with palovarotene 5 mg daily for up to 24 months. Participants with flare-ups received palovarotene 20 mg daily for 4 weeks followed by 10 mg daily for 8 weeks. In Part C, eligible participants received chronic treatment of palovarotene 5mg daily for up to 36 months. Participants with flare-ups received palovarotene 20 mg daily for 4 weeks followed by 10 mg daily for 8 weeks. For skeletal immature participants, the exposure-equivalent dose was determined based on weight. In Part D, no study drug was administered. Participants in Part C/D were followed for up to an additional 48 months.
Overall Study STARTED	58
Overall Study Entered Part A	40
Overall Study Completed Part A	13
Overall Study Entered Part B	54
Overall Study Completed Part B	16
Overall Study Entered Part C	48
Overall Study Completed Part C	29
Overall Study Entered Part D	2
Overall Study COMPLETED	39
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Reasons for withdrawal
Measure	All Participants Participants who completed PVO-1A-201 study were followed for up to 36 months in Part A. Eligible participants with a flare-up received palovarotene 10 milligram (mg) capsule orally daily for 2 weeks followed by 5 mg daily for 4 weeks during the flare-up component of Part A. In Part B, eligible participants from Part A and participants from the new Adult Cohort received chronic treatment with palovarotene 5 mg daily for up to 24 months. Participants with flare-ups received palovarotene 20 mg daily for 4 weeks followed by 10 mg daily for 8 weeks. In Part C, eligible participants received chronic treatment of palovarotene 5mg daily for up to 36 months. Participants with flare-ups received palovarotene 20 mg daily for 4 weeks followed by 10 mg daily for 8 weeks. For skeletal immature participants, the exposure-equivalent dose was determined based on weight. In Part D, no study drug was administered. Participants in Part C/D were followed for up to an additional 48 months.
Overall Study Non-Compliance	1
Overall Study Withdrawal by Subject	8
Overall Study Adverse Event	2
Overall Study Other	7
Overall Study Lost to Follow-up	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	All Participants n=58 Participants Participants who completed PVO-1A-201 study were followed for up to 36 months in Part A. Eligible participants with a flare-up received palovarotene 10 mg capsule orally daily for 2 weeks followed by 5 mg daily for 4 weeks during the flare-up component of Part A. In Part B, eligible participants from Part A and participants from the new Adult Cohort received chronic treatment with palovarotene 5 mg daily for up to 24 months. Participants with flare-ups received palovarotene 20 mg daily for 4 weeks followed by 10 mg daily for 8 weeks. In Part C, eligible participants received chronic treatment of palovarotene 5 mg daily for up to 36 months. Participants with flare-ups received palovarotene 20mg daily for 4 weeks followed by 10 mg daily for 8 weeks. For skeletal immature participants, the exposure-equivalent dose was determined based on weight. In Part D, no study drug was administered. Participants in Part C/D were followed for up to an additional 48 months.
Age, Continuous	21.0 years STANDARD_DEVIATION 9.27 • n=58 Participants
Sex: Female, Male Female	32 Participants n=58 Participants
Sex: Female, Male Male	26 Participants n=58 Participants

PRIMARY outcome

Timeframe: Baseline and Week 12

Population: Part A: Efficacy population included all participants in the treated population who had an evaluable Week 6 or Week 12 image \[computed tomography (CT) scan or plain radiograph\]. Part B: Flare-up population included all participants in the treated population who took at least 1 dose of palovarotene during flare-up based treatment in Part B. Only participants with flare-ups at baseline and Week 12 are reported.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=28 Flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=51 Flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Percentage of Flare-ups With No New Heterotopic Ossification (HO) at Week 12	64.3 percentage of flare-ups	72.5 percentage of flare-ups	—	—	—	—	—	—

PRIMARY outcome

Timeframe: From Baseline (Day 1) up to end of 2 year follow-up period, approximately a maximum of 96 months

Population: The Full Analysis Set (FAS) included all enrolled participants having a baseline HO volume measurement and at least 1 post-baseline HO volume measurement in the PVO-1A-202 study.

The annualized change in new HO volume was assessed by low-dose whole body computed tomography (WBCT) scan, excluding head. Results are presented for overall intent to treat (ITT) period.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=4 Participants Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=24 Participants Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups n=9 Participants Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined n=13 Participants Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups n=8 Participants Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups n=6 Participants At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups n=7 Participants No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined n=15 Participants This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts B and C: Annualized Change in New HO Volume	-3464.0 cubic millimeter (mm^3)/year Standard Deviation 5081.50	29522.8 cubic millimeter (mm^3)/year Standard Deviation 89408.15	25041.1 cubic millimeter (mm^3)/year Standard Deviation 58529.79	16270.3 cubic millimeter (mm^3)/year Standard Deviation 49777.40	-10343.4 cubic millimeter (mm^3)/year Standard Deviation 18007.89	52291.4 cubic millimeter (mm^3)/year Standard Deviation 86019.62	30530.9 cubic millimeter (mm^3)/year Standard Deviation 51800.47	8731.3 cubic millimeter (mm^3)/year Standard Deviation 41924.30

SECONDARY outcome

Timeframe: Part A: Baseline (pre-dose data from Study PVO-1A-201 for follow-up component and flare-up screening/Day 1 for flare-up component) and Month 12; Part B: Baseline (flare-up screening/baseline) and Weeks 6 and 12

Population: No participants were analyzed for this endpoint.

The HO score ranged 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. Highest HO score from 2 projections was used.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Month 12

Population: Part A: The Efficacy population included all participants in the treated population who had an evaluable Week 6 or Week 12 image (CT scan or plain radiograph). Part B: The Flare-up population included all participants in the treated population who took at least 1 dose of palovarotene during flare-up based treatment in Part B. Only participants with flare-ups at Week 12 are reported.

Plain radiographs were utilized in Part A of the study. The interpretation of radiographs was to have documented the absence or presence of new HO at the flare-up site compared with the baseline assessment, and the volume of new HO if present. Low-dose CT scans were utilized in Part B of the study. Low-dose, flare-up site-specific CT scan was used as the primary imaging assessment of HO for flare-ups and low-dose, WBCT scans were used as the primary imaging assessment for total body HO in those participants receiving chronic treatment.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=26 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=48 Number of flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Volume of New Heterotopic Bone Formed at Month 12	2310 mm^3 Standard Deviation 4739	4818 mm^3 Standard Deviation 17349	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Part A and B: At Week 12

Population: Part A: The Efficacy population. Part B: The Flare-up population. The data collected for flare-ups used each flare-up as the unit of analysis rather than each participant. Additionally, a study participant may have not had any flare-ups whereas another participant may have had multiple flare-ups (note, the number of flare-ups can be larger than the number of participants OR it can be smaller OR it can match, by chance).

Blood and urine samples for cartilage, bone, angiogenesis, and inflammation biomarkers were evaluated during Part A and Part B of the study. Bone and cartilage biomarkers included: osteocalcin, bone-specific alkaline phosphatase (ALP), procollagen type 1-N-terminal pro-peptide (PINP), cartilage-derived (CD) retinoic acid protein, procollagen type 1-C-terminal pro-peptide (PICP), and C-terminal telopeptide. Angiogenesis included urinary basic fibroblast growth factor. Inflammation included erythrocyte sedimentation rate, C-reactive protein, Interleukin(IL)-6, IL-1 beta, tumor necrosis factor (TNF)-alpha, creatine phosphokinase, and lactate dehydrogenase. Based on emerging data from studies PVO-1A-001, PVO-1A-201, and Parts A and B of PVO-1A-202, biomarkers were removed from the evaluation during Part C.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=26 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=46 Number of flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: Osteocalcin	10 number of flare-ups	6 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: Bone-specific ALP	2 number of flare-ups	2 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: P1NP	10 number of flare-ups	2 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: CD retinoic acid protein	4 number of flare-ups	6 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: P1CP	3 number of flare-ups	2 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: C-terminal telopeptide	0 number of flare-ups	1 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: Urinary basic FGF	6 number of flare-ups	5 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: ESR	4 number of flare-ups	0 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: C-reactive protein	6 number of flare-ups	5 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: IL-6	0 number of flare-ups	3 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: IL-1 beta	5 number of flare-ups	5 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: TNF-alpha	3 number of flare-ups	1 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: Creatine kinase	1 number of flare-ups	3 number of flare-ups	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 Parts A and B: Lactate dehydrogenase	4 number of flare-ups	1 number of flare-ups	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Part A: Efficacy population included all participants in the treated population who had an evaluable Week 6 or Week 12 image (CT scan or plain radiograph). Part B: Flare-up population included all participants in the treated population who took at least 1 dose of palovarotene during flare-up based treatment in Part B. Only participants with flare-ups at baseline and Week 12 are reported.

Active ROM was assessed by goniometer in Parts A and B of the study. Measurements were performed by trained and qualified study personnel (eg, physiotherapist) in order to standardize the performance of procedures and minimize variability. Flare-ups at the primary joint was expressed as percent of normal arc of motion. Based on the change in the schedule for flare-up based assessments. Baseline was defined as pre-dose data from Study PVO-1A-201 for follow-up component and flare-up screening/Day 1 for flare-up component for Part A and flare-up screening/baseline for Part B.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=27 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=49 Number of flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Change From Baseline in Active Range of Motion (ROM) at Flare-up Site at Week 12	-6.16 percent of normal total arc of motion Standard Deviation 14.362	-0.49 percent of normal total arc of motion Standard Deviation 18.096	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Week 12

Population: Flare-up population. The data collected for flare-ups used each flare-up as unit of analysis rather than each participant. Additionally, a study participant may have not had any flare-ups whereas another participant may have had multiple flare-ups (note, the number of flare-ups can be larger than the number of participants OR it can be smaller OR it can match, by chance). Only participants with flare-ups at baseline and at each time point are reported.

The ROM was assessed by the Investigator using Cumulative Analogue Joint Involvement Scale (CAJIS) for participants in Part B. It includes 12 joints (shoulder, elbow, wrist, hip, knee, and ankle on both the right and left sides), and 3 body regions (jaw, cervical spine \[neck\], and thoracic/lumbar spine). Each joint/region was assessed as: 0=uninvolved; 1=partially involved; and 2=completely ankylosed. The total score range is 0 (no involvement) to 30 (maximally involved). Baseline was flare-up screening.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=51 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part B: Change From Baseline in ROM at Week 12	0.3 units on a scale Standard Deviation 1.80	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Months 6, 12, 18, 24, 30, 36, 42, and 48

Population: The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in the PVO-1A-202 study. Only participants analyzed at baseline and specific time point are reported.

The ROM was assessed by the Investigator using CAJIS for participants in Part C. It includes 12 joints (shoulder, elbow, wrist, hip, knee, and ankle on both the right and left sides), and 3 body regions (jaw, cervical spine \[neck\], and thoracic/lumbar spine). Each joint/region was assessed as: 0=uninvolved; 1=partially involved; and 2=completely ankylosed. The total score range is 0 (no involvement) to 30 (maximally involved). Baseline was chronic Day 1.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=34 Participants Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 6	0.2 units on a scale Standard Deviation 1.58	—	—	—	—	—	—	—
Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 12	0.6 units on a scale Standard Deviation 1.76	—	—	—	—	—	—	—
Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 18	0.9 units on a scale Standard Deviation 1.73	—	—	—	—	—	—	—
Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 24	1.3 units on a scale Standard Deviation 2.74	—	—	—	—	—	—	—
Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 30	1.5 units on a scale Standard Deviation 2.79	—	—	—	—	—	—	—
Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 36	1.6 units on a scale Standard Deviation 3.38	—	—	—	—	—	—	—
Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 42	1.6 units on a scale Standard Deviation 3.03	—	—	—	—	—	—	—
Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 48	3.0 units on a scale Standard Deviation 2.55	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 12

Population: The Flare-up population. The data collected for flare-ups used each flare-up as the unit of analysis rather than each participant. Additionally, a study participant may have not had any flare-ups whereas another participant may have had multiple flare-ups (note, the number of flare-ups can be larger than the number of participants OR it can be smaller OR it can match, by chance). Only participants with flare-ups at baseline and Week 12 are reported.

Participants/Investigators assessed how the flare-up was affecting movement (better, same, slightly worse, moderately worse, or severely worse movement) compared with baseline. Based on the change in the schedule for flare-up based assessments. PA = Participant assessment and IA = Investigator assessment.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=51 Flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: New HO - Same movement	3 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: New HO - Better movement	5 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: New HO - Same movement	3 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: New HO - Slightly worse movement	2 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: New HO - Moderately worse movement	2 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: New HO - Severely worse movement	2 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: No new HO - Better movement	11 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: No new HO - Same movement	20 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: No new HO - Slightly worse movement	5 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: No new HO - Moderately worse movement	1 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 PA: No new HO - Severely worse movement	0 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: New HO - Better movement	5 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: New HO - Slightly worse movement	2 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: New HO - Moderately worse movement	3 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: New HO - Severely worse movement	1 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: No new HO - Better movement	1 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: No new HO - Same movement	29 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: No new HO - Slightly worse movement	6 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: No new HO - Moderately worse movement	1 number of flare-ups	—	—	—	—	—	—	—
Part B: Participant and Investigator Global Assessment of Movement at Week 12 IA: No new HO - Severely worse movement	0 number of flare-ups	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Weeks 2, 4, 6, 9, and 12

Population: The Efficacy population. The data collected for flare-ups used each flare-up as unit of analysis rather than each participant. Additionally, a study participant may have not had any flare-ups whereas another participant may have had multiple flare-ups (note, number of flare-ups can be larger than the number of participants OR it can be smaller OR it can match, by chance). Only participants with flare-ups at baseline and at each time point are reported.

The NRSs for pain and swelling were used in Part A of the study to evaluate the effect of palovarotene on pain and swelling at the flare-up site. Flare-up pain was rated on a scale ranging from 0 (no pain or swelling) to 10 (worst pain or swelling ever experienced). For children less than 8 years old, pain was rated using the FPS-R, which ranging from 0 to 10 in 2-point increments where 0 = no pain and 10 = very much pain. Flare-up swelling was rated on a scale from 0 to 10 where 0 = no swelling and 10 = worst swelling ever experienced. Higher scores indicate worst quality of life for all scales. Baseline was predose data from PVO-1A-201 study/flare-up screening/Day 1.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=28 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 2: Pain	-1.4 units on a scale Standard Deviation 2.22	—	—	—	—	—	—	—
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 4: Pain	-2.1 units on a scale Standard Deviation 2.27	—	—	—	—	—	—	—
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 6: Pain	-2.6 units on a scale Standard Deviation 2.71	—	—	—	—	—	—	—
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 9: Pain	-2.9 units on a scale Standard Deviation 2.97	—	—	—	—	—	—	—
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 12: Pain	-2.6 units on a scale Standard Deviation 2.85	—	—	—	—	—	—	—
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 2: Swelling	-1.7 units on a scale Standard Deviation 1.83	—	—	—	—	—	—	—
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 4: Swelling	-2.3 units on a scale Standard Deviation 2.31	—	—	—	—	—	—	—
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 6: Swelling	-2.4 units on a scale Standard Deviation 2.38	—	—	—	—	—	—	—
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 9: Swelling	-2.7 units on a scale Standard Deviation 2.47	—	—	—	—	—	—	—
Part A: Change From Baseline in Numeric Rating Scale (NRS) Pain and Swelling or Faces Pain Scale-Revised (FPS-R) at Weeks 2, 4, 6, 9, and 12 Week 12: Swelling	-2.9 units on a scale Standard Deviation 2.46	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Part A: Baseline and Weeks 2, 4, 6, 9, and 12; and Part B: Baseline and Weeks 4, 8, and 12

Population: Part A: Efficacy population. Part B: Flare-up population. Data collected for flare-ups used each flare-up as unit of analysis rather than each participant. A study participant may have not had any flare-ups whereas another participant may have had multiple flare-ups (number of flare-ups can be larger than number of participants OR it can be smaller OR it can match, by chance). Only participants with flare-ups at baseline and at each time point are reported.

The effect of palovarotene on physical function was determined using Fibrodysplasia Ossificans Progressiva-Physical Function Questionnaire (FOP-PFQ). The questionnaire consisted of 28 items ranging from 1 (not able to do) to 5 (with no trouble; without help or assistive device). Total score range from 28 to 140. Lower scores denoted more difficulty, with items categorized into upper extremity and mobility sections.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=28 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=52 Number of flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Change From Baseline in Physical Function at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: Week 9	0.76 units on a scale Standard Deviation 6.054	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical Function at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: Week 12	0.69 units on a scale Standard Deviation 6.604	0.17 units on a scale Standard Deviation 6.893	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical Function at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: Week 2	-0.97 units on a scale Standard Deviation 4.939	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical Function at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: Week 4	0.38 units on a scale Standard Deviation 4.746	-1.23 units on a scale Standard Deviation 4.453	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical Function at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: Week 6	0.21 units on a scale Standard Deviation 6.501	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical Function at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: Week 8	—	0.88 units on a scale Standard Deviation 9.357	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Months 6, 12, 18, 24, 30, 36, 42, and 48

The effect of palovarotene on physical function was determined using FOP-PFQ. The questionnaire consisted of 28 items ranging from 1 (not able to do) to 5 (with no trouble; without help or assistive device). Total score range from 28 to 140. Lower scores denoted more difficulty, with items categorized into upper extremity and mobility sections.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=36 Participants Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 6	1.8 units on a scale Standard Deviation 6.36	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 12	1.8 units on a scale Standard Deviation 9.81	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 18	4.0 units on a scale Standard Deviation 9.49	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 24	7.5 units on a scale Standard Deviation 14.00	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 30	8.2 units on a scale Standard Deviation 13.45	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 36	9.8 units on a scale Standard Deviation 14.11	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 42	7.0 units on a scale Standard Deviation 13.14	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48 Month 48	8.3 units on a scale Standard Deviation 7.76	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Part A: Baseline and Weeks 2, 4, 6, 9, and 12; and Part B: Baseline and Weeks 4, 8, and 12

The patient reported outcomes measurement information system (PROMIS) global health scale was administered to evaluate the effect of palovarotene on physical and mental health in participants ≥15 years of age and mental health in participants \<15 years of age, age-appropriate forms of the PROMIS global health scales were administered. A T-score of 50 is normal and increments of 10 are +/- standard deviation away from the norm. A T-score \<50 indicates worse health, while a T-score \>50 indicates better health. Higher values (positive changes) indicate better health. AFPH = Adult Form, Physical Health; AFMH = Adult Form, Mental Health; PFH = Paediatric Form, Health.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=28 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=52 Number of flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFPH - Week 2	3.26 units on a scale Standard Deviation 4.819	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFPH - Week 4	2.14 units on a scale Standard Deviation 3.976	0.2 units on a scale Standard Deviation 3.17	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFPH - Week 6	1.78 units on a scale Standard Deviation 3.735	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFPH - Week 8	—	0.3 units on a scale Standard Deviation 3.33	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFPH - Week 9	2.87 units on a scale Standard Deviation 5.352	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFPH - Week 12	3.22 units on a scale Standard Deviation 4.855	0.6 units on a scale Standard Deviation 3.79	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFMH - Week 2	1.00 units on a scale Standard Deviation 4.667	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFMH - Week 4	0.39 units on a scale Standard Deviation 3.264	1.0 units on a scale Standard Deviation 8.05	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFMH - Week 6	1.03 units on a scale Standard Deviation 3.122	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFMH - Week 8	—	-0.3 units on a scale Standard Deviation 7.47	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFMH - Week 9	-0.16 units on a scale Standard Deviation 4.422	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: AFMH - Week 12	0.99 units on a scale Standard Deviation 2.915	0.2 units on a scale Standard Deviation 7.63	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: PFH - Week 2	-0.05 units on a scale Standard Deviation 2.475	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: PFH - Week 4	1.70 units on a scale Standard Deviation 4.950	0.7 units on a scale Standard Deviation 4.77	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: PFH - Week 6	5.25 units on a scale Standard Deviation 4.596	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: PFH - Week 8	—	-2.5 units on a scale Standard Deviation 6.32	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: PFH - Week 9	0.85 units on a scale Standard Deviation 1.202	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Physical and Mental Health at Weeks 2, 4, 6, 9, and 12 of Part A; and Weeks 4, 8, and 12 of Part B Parts A and B: PFH - Week 12	0.85 units on a scale Standard Deviation 3.748	0.4 units on a scale Standard Deviation 5.65	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Months 6, 12, 18, 24, 30, 36, 42, and 48

The PROMIS global health scale was administered to evaluate the effect of palovarotene on physical and mental health in participants ≥15 years of age and mental health in participants \<15 years of age, age-appropriate forms of the PROMIS global health scales were administered. A T-score of 50 is normal and increments of 10 are +/- standard deviation away from the norm. A T-score \<50 indicates worse health, while a T-score \>50 indicates better health. Higher values (positive changes) indicate better health. AFPH = Adult Form, Physical Health; AFMH = Adult Form, Mental Health; PFH = Paediatric Form, Health.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=30 Participants Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFPH - Month 6	-0.2 units on a scale Standard Deviation 5.59	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFPH - Month 12	0.6 units on a scale Standard Deviation 6.04	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFPH - Month 18	-0.1 units on a scale Standard Deviation 5.30	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFPH - Month 24	-1.1 units on a scale Standard Deviation 7.10	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFPH - Month 30	0.1 units on a scale Standard Deviation 4.46	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFPH - Month 36	-1.1 units on a scale Standard Deviation 5.97	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFPH - Month 42	-1.8 units on a scale Standard Deviation 6.55	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFPH - Month 48	-1.6 units on a scale Standard Deviation 3.02	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFMH - Month 6	-2.2 units on a scale Standard Deviation 6.49	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFMH - Month 12	-0.0 units on a scale Standard Deviation 3.96	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFMH - Month 18	-0.8 units on a scale Standard Deviation 5.04	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFMH - Month 24	-2.5 units on a scale Standard Deviation 5.96	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFMH - Month 30	-3.0 units on a scale Standard Deviation 5.30	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFMH - Month 36	-1.5 units on a scale Standard Deviation 4.95	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFMH - Month 42	-2.9 units on a scale Standard Deviation 6.24	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 AFMH - Month 48	-5.2 units on a scale Standard Deviation 7.83	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 PFH - Month 6	3.8 units on a scale Standard Deviation 2.91	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 PFH - Month 12	1.7 units on a scale Standard Deviation 1.65	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 PFH - Month 18	4.7 units on a scale Standard Deviation 1.93	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 PFH - Month 24	3.4 units on a scale Standard Deviation 4.63	—	—	—	—	—	—	—
Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 PFH - Month 30	4.6 units on a scale Standard Deviation 2.52	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Part A: Weeks 6 and 12; and Part B: Week 12

Population: Part A: The Efficacy population. Part B: The Flare-up population. Only participants with flare-ups at baseline and at each time point are reported.

The FOP assistive devices and adaptations questionnaire was used in Part A and Part B of the study. Assistive devices and adaptations were grouped into the following categories: 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. When a flare-up did not use an assistive device or adaptation or considered the assistive device or adaptation not applicable, 0 was imputed for analysis.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=28 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=52 Number of flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Number of Any Assistive Devices and Adaptations by FOP Participants at Weeks 6 and 12 of Part A; and Week 12 of Part B Part A: Week 6	12.9 devices adaptations Standard Deviation 11.52	—	—	—	—	—	—	—
Parts A and B: Number of Any Assistive Devices and Adaptations by FOP Participants at Weeks 6 and 12 of Part A; and Week 12 of Part B Parts A and B: Week 12	14.3 devices adaptations Standard Deviation 12.39	13.2 devices adaptations Standard Deviation 10.50	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Week 12

Population: The Efficacy population included all participants in the treated population who had an evaluable Week 6 or Week 12 image (CT scan or plain radiograph). Only participants with flare-ups at baseline and Week 12 are reported.

A responder was defined as a participant with no or minimal new HO at original flare-up site compared with baseline (flare-up screening/Day 1). Minimal new HO was defined as new HO with an HO score \<=3 in both the AP and lateral projections (or if 1 view is non-interpretable or non-evaluable, then remaining evaluable view was used). The HO score ranged 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. Highest HO score from 2 projections was used. Results from the Primary Read reviews are presented.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=28 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part A: Percentage of Responders at Week 12	64.3 percentage of participants	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Part A: Baseline and Weeks 6 and 12; and Part B: Baseline and Week 12

Population: Part A: The Efficacy population. Part B: The Flare-up population. The data collected for flare-ups used each flare-up as unit of analysis rather than each participant. Additionally, a study participant may have not had any flare-ups whereas another participant may have had multiple flare-ups (note, number of flare-ups can be larger than the number of participants OR it can be smaller OR it can match, by chance). Only participants with flare-ups at baseline and at each time point are reported.

The bone formation was measured by PINP biomarker. Baseline was defined as flare-up screening/Day 1.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=28 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=52 Number of flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Change From Baseline in Amount of Bone Formation Biomarker at Weeks 6 and 12 of Part A; and Week 12 of Part B Part A: Week 6	38.755 microgram per liter Standard Deviation 50.547	—	—	—	—	—	—	—
Parts A and B: Change From Baseline in Amount of Bone Formation Biomarker at Weeks 6 and 12 of Part A; and Week 12 of Part B Parts A and B: Week 12	54.592 microgram per liter Standard Deviation 140.540	70.916 microgram per liter Standard Deviation 130.608	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Part A: Baseline and Weeks 6 and 12; and Part B: Baseline and Week 12

Magnetic resonance imaging (MRI) was utilized as an imaging modality to evaluate for the presence of soft tissue swelling/edema and cartilage formation for participants who received flare-up based treatment. Ultrasound (US) was utilized to evaluate for the presence of soft tissue swelling in participants unable to undergo MRI. Both MRI and US were interpreted centrally. When US was used, cartilage formation was not assessed.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=28 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=52 Number of flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Number of Flare-ups With Soft Tissue Swelling and/or Cartilage Formation at Weeks 6 and 12 of Part A; and Week 12 of Part B Part A: Edema - Week 6	7 flare-up	—	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Soft Tissue Swelling and/or Cartilage Formation at Weeks 6 and 12 of Part A; and Week 12 of Part B Part A: Cartilage Formation - Week 6	0 flare-up	—	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Soft Tissue Swelling and/or Cartilage Formation at Weeks 6 and 12 of Part A; and Week 12 of Part B Parts A and B: Edema - Week 12	9 flare-up	36 flare-up	—	—	—	—	—	—
Parts A and B: Number of Flare-ups With Soft Tissue Swelling and/or Cartilage Formation at Weeks 6 and 12 of Part A; and Week 12 of Part B Parts A and B: Cartilage Formation - Week 12	0 flare-up	1 flare-up	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Part A: From Baseline up to 36 months; and Part B: From Baseline up to 24 months

The number of days of active symptomatic flare-up was the number of days the participant reported the presence of symptoms in the diary.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=24 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined n=48 Number of flare-ups Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Parts A and B: Duration of Active Symptomatic Flare-up	27.1 day Standard Deviation 29.9	39.5 day Standard Deviation 36.1	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Baseline and Months 12 and 24

Population: The WBCT Population included participants who received chronic dosing and had baseline and Month 12 WBCT scans. Only participants analyzed at baseline and specific time point are reported.

Whole body burden of HO was assessed by low-dose WBCT scan, excluding head. Baseline was Part B Screening.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=37 Participants Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part B: Change From Baseline in Whole Body Burden of HO at Months 12 and 24 Month 12	28386 mm^3 Standard Deviation 89918	—	—	—	—	—	—	—
Part B: Change From Baseline in Whole Body Burden of HO at Months 12 and 24 Month 24	193150 mm^3 Standard Deviation 9999	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to end of 2 year follow-up period, approximately a maximum of 96 months

Population: The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in the PVO-1A-202 study.

Flare-ups were counted using the number of participant/Investigator-reported flare-ups. Percentage was calculated by dividing the total number of flare-ups by the total participant months of follow-up. Results are presented for overall ITT period.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=52 Number of flare-ups Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part B: Mean Percentage of Flare-ups Per Participant-Month Overall	0.12 percentage of flare-up/participant-month Standard Deviation 0.124	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: From Baseline (Day 1) up to end of 2 year follow-up period, approximately a maximum of 96 months

Population: The Safety analysis set included all enrolled participants who received at least 1 dose of palovarotene in the PVO-1A-202 study.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=46 Participants Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part C: Mean Percentage of Flare-ups Per Participant-Month Overall	0.14 percentage of flare-up/participant-month Standard Deviation 0.150	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Months 12, 24, 36, 60, and 72 (last visit)

Population: The FAS included all enrolled participants having a baseline HO volume measurement and at least 1 post-baseline HO volume measurement in the PVO-1A-202 study.

New HO was defined as total WBCT new HO volume \>0. Results for Month 72 are presented for overall ITT period.

Outcome measures

Outcome measures
Measure	Part A: Palovarotene 10/5 mg - Flare-up n=46 Participants Participants received palovarotene 10 mg for 14 days followed by 5 mg for 28 days during flare-ups (10/5-mg regimen). The participants were followed for an additional 42 days without treatment.	Part B: Flare-up Combined Skeletally mature participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups (20/10-mg regimen) and 5 mg daily when not taking flare-up dosing. Treatment may have been extended if the flare-up was ongoing and continued until the flare-up resolved. Dosing was extended in 4-week intervals and was based on clinical signs and symptoms as assessed by the Investigator.	Part B: No Flare-ups Participants received palovarotene 5 mg daily. No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part B: All Treated and No Flare-ups Combined Participants received palovarotene 20 mg for 28 days followed by 10 mg for 56 days during flare-ups and with 5 mg daily when not taking flare-up dosing for skeletally mature participants. This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B).	Part C: Palovarotene - All Treated Flare-ups Participants received palovarotene 5 mg daily and 20 mg for 28 days followed by 10 mg for 56 days during flare-ups. Participants were treated for all flare-ups. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: Untreated/Undertreated Flare-ups At least 1 flare-up was untreated/undertreated. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: No Flare-ups No flare-ups were reported. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).	Part C: All Treated and No Flare-ups Combined This group pools data from all participants irrespective of treatment. The change in new HO total volume was compared to baseline where the baseline value was performed prior to the initiation of non-flare-up based dosing (in Part B or Part C).
Part C: Percentage of Participants With New HO at Months 12, 24, 36, 60, and 72 (Last Visit) Month 12	60.0 percentage of participants	—	—	—	—	—	—	—
Part C: Percentage of Participants With New HO at Months 12, 24, 36, 60, and 72 (Last Visit) Month 24	54.5 percentage of participants	—	—	—	—	—	—	—
Part C: Percentage of Participants With New HO at Months 12, 24, 36, 60, and 72 (Last Visit) Month 36	61.5 percentage of participants	—	—	—	—	—	—	—
Part C: Percentage of Participants With New HO at Months 12, 24, 36, 60, and 72 (Last Visit) Month 60	100.0 percentage of participants	—	—	—	—	—	—	—
Part C: Percentage of Participants With New HO at Months 12, 24, 36, 60, and 72 (Last Visit) Month 72	86.2 percentage of participants	—	—	—	—	—	—	—

Adverse Events

Part A

Serious events: 2 serious events

Other events: 20 other events

Deaths: 0 deaths

Part B

Serious events: 9 serious events

Other events: 52 other events

Deaths: 0 deaths

Part C

Serious events: 25 serious events

Other events: 46 other events

Deaths: 0 deaths

Part D

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Medical Director

Ipsen

Phone: see email

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place