Phase 3
N=61
A Rollover Study to Further Evaluate the Safety and Efficacy of Palovarotene Capsules in Male and Female Participants Aged ≥14 Years With Fibrodysplasia Ossificans Progressiva (FOP) Who Have Completed the Relevant Parent Studies.
Fibrodysplasia Ossificans Progressiva (FOP)
Bottom Line
View on ClinicalTrials.gov: NCT05027802 ↗Enrolled (actual)
61
Serious AEs
15.3%
Results posted
Jun 2025
Primary outcome: Primary: Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events — 54; 9; 53; 1 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Palovarotene (Drug)
- Age
- Pediatric, Adult, Older Adult · 14+ yrs
- Sex
- All
- Sponsor
- Ipsen
- Primary completion
- Nov 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With All Treatment-emergent Adverse Events (TEAEs), Serious and Non-serious Treatment-emergent Adverse Events and Serious and Non-serious Treatment-related Treatment-emergent Adverse Events |
54; 9; 53; 1; 38 | — |
| SECONDARY Change From the Inclusion Visit in Cumulative Analogue Joint Involvement Scale (CAJIS) Total Score at Months 6, 12, 18, 24 and 30 |
0.6; 1.1; 1.5; 1.5; 2.0 | — |
| SECONDARY Change From the Inclusion Visit in the Use of Assistive Devices and Adaptations (Aids) for Daily Living at Months 6, 12, 18, 24 and 30 |
-0.7; 1.1; 1.4; 1.2; 2.8 | — |
| SECONDARY Change From the Inclusion Visit in Percentage of Worst Score Using the Adult Form of the Fibrodysplasia Ossificans Progressiva Physical Function Questionnaire (FOP-PFQ) at Months 6, 12, 18, 24 and 30 |
0.74; 2.39; 4.77; 7.80; 13.79; 0.70 | — |
| SECONDARY Annualized Rate of Healthcare Utilization (HU) in Participants With Fibrodysplasia Ossificans Progressiva |
21.7 | — |
| SECONDARY Change From the Inclusion Visit in Percent Predicted Forced Vital Capacity (FVC) at Months 6, 12, 18, 24 and 30 |
1.2; -0.7; -3.9; -1.6; -2.8 | — |
| SECONDARY Change From the Inclusion Visit in Percent Predicted Forced Expiratory Volume in One Second (FEV1) at Months 6, 12, 18, 24 and 30 |
1.8; -3.1; -5.3; -3.8; -10.0 | — |
| SECONDARY Change From the Inclusion Visit in Predicted FEV1/FVC Ratio at Months 6, 12, 18, 24 and 30 |
0.0163; -0.0323; -0.0137; -0.0365; -0.1268 | — |
| SECONDARY Change From the Inclusion Visit in Percent Predicted Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) at Months 6, 12, 18, 24 and 30 |
-1.5; -5.3; -4.4; -4.8; -20.0 | — |
| SECONDARY Change From the Inclusion Visit in Physical and Mental Function Using Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at Months 6, 12, 18, 24 and 30 |
-0.6; -1.7; -2.9; -1.9; -3.9; -1.0 | — |
| SECONDARY Number of Participants With Flare-ups and Flare-up Outcomes |
27; 26; 15; 4; 7; 4 | — |
| SECONDARY Number of Participants With Flare-ups by Body Location |
8; 3; 5; 5; 3; 4 | — |
| SECONDARY Duration of Flare-up at Months 6, 12, 18 and 24 |
130.7; 121.7; 72.4; 72.3 | — |
| SECONDARY Percentage of Participants With Extra Bone Growth at Months 6, 12, 18 and 24 |
8.5; 3.4; 8.5; 8.5; 1.7; 3.4 | — |
Summary
The main objective of this study is to further evaluate the safety and efficacy of palovarotene in adult and paediatric participants with FOP.
The aim of the study is also to ensure treatment continuity to participants who have completed one of the parent studies (Study PVO-1A-301, Study PVO-1A-202 and Study PVO-1A-204) and who, in the investigator's judgement, may benefit from palovarotene therapy.
Eligibility Criteria
Inclusion Criteria
- Participant has completed the EOS or End of Treatment Visit of Study PVO-1A-301 or PVO-1A-202 (PVO-1A-202 Parts C and D correspond to Study PVO-1A-204 in France) and did not previously withdraw consent from any of the parent studies to be eligible for Study CLIN-60120-452.
- Participant must be ≥14 years of age (aligned with the age of treated participants in the ongoing parent studies PVO-1A-301 and PVO-1A-202/PVO-1A-204) and qualify as 100% skeletally mature (if 2× above the upper limit of normal (ULN) or with a history of chronic pancreatitis.
- Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5× ULN.
- Fasting triglycerides >400 mg/dL with or without therapy.
- Suicidal ideation (type 4 or 5) or any suicidal behaviour at the Inclusion Visit as defined by the Columbia-Suicide Severity Rating Scale (C-SSRS).
- Current use of vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, or herbal preparations, fish oil, and unable or unwilling to discontinue use of these products during palovarotene treatment.
- Exposure to synthetic oral retinoids other than palovarotene within 4 weeks of the Inclusion Visit.
- Concurrent treatment with tetracycline or any tetracycline derivatives due to the potential increased risk of pseudotumor cerebri.
- Use of concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity; or kinase inhibitors such as imatinib.
- Palovarotene is reimbursed in the country where the study is being conducted.
- Any reason that, in the opinion of the investigator, would lead to the inability of the participant and/or family to comply with the protocol.
Data sourced from ClinicalTrials.gov (NCT05027802). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.