Phase 2
N=58
An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP)
Fibrodysplasia Ossificans Progressiva
Bottom Line
View on ClinicalTrials.gov: NCT02279095 ↗Enrolled (actual)
58
Serious AEs
30.3%
Results posted
May 2024
Primary outcome: Primary: Parts A and B: Percentage of Flare-ups With No New Heterotopic Ossification (HO) at Week 12 — 64.3; 72.5 percentage of flare-ups
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Palovarotene dose level 1 (Drug); Palovarotene dose level 2 (Drug); Palovarotene dose level 3 (Drug); Palovarotene dose level 4 (Drug)
- Age
- Pediatric, Adult, Older Adult · 6+ yrs
- Sex
- All
- Sponsor
- Clementia Pharmaceuticals Inc.
- Primary completion
- Sep 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Parts A and B: Percentage of Flare-ups With No New Heterotopic Ossification (HO) at Week 12 |
64.3; 72.5 | — |
| PRIMARY Parts B and C: Annualized Change in New HO Volume |
-3464.0; 29522.8; 25041.1; 16270.3; -10343.4; 52291.4 | — |
| SECONDARY Parts A and B: Percentage of Participants Across the 7 HO Scores at Month 12 of Part A; and Weeks 6 and 12 for Part B |
— | — |
| SECONDARY Parts A and B: Volume of New Heterotopic Bone Formed at Month 12 |
2310; 4818 | — |
| SECONDARY Parts A and B: Number of Flare-ups With Significant Abnormalities in Cartilage, Bone, Angiogenesis, and Inflammation Biomarkers at Week 12 |
10; 6; 2; 2; 10; 2 | — |
| SECONDARY Parts A and B: Change From Baseline in Active Range of Motion (ROM) at Flare-up Site at Week 12 |
-6.16; -0.49 | — |
| SECONDARY Part B: Change From Baseline in ROM at Week 12 |
0.3 | — |
| SECONDARY Part C: Change From Baseline in ROM at Months 6, 12, 18, 24, 30, 36, 42, and 48 |
0.2; 0.6; 0.9; 1.3; 1.5; 1.6 | — |
| SECONDARY Part B: Participant and Investigator Global Assessment of Movement at Week 12 |
5; 3; 2; 2; 2; 11 | — |
| SECONDARY 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 |
-1.4; -2.1; -2.6; -2.9; -2.6; -1.7 | — |
| SECONDARY 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 |
-0.97; 0.38; -1.23; 0.21; 0.88; 0.76 | — |
| SECONDARY Part C: Change From Baseline in Physical Function at Months 6, 12, 18, 24, 30, 36, 42, and 48 |
1.8; 1.8; 4.0; 7.5; 8.2; 9.8 | — |
| SECONDARY 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 |
3.26; 2.14; 0.2; 1.78; 0.3; 2.87 | — |
| SECONDARY Part C: Change From Baseline in Physical and Mental Health at Months 6, 12, 18, 24, 30, 36, 42, and 48 |
-0.2; 0.6; -0.1; -1.1; 0.1; -1.1 | — |
| SECONDARY 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 |
12.9; 14.3; 13.2 | — |
| SECONDARY Part A: Percentage of Responders at Week 12 |
64.3 | — |
| SECONDARY 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 |
38.755; 54.592; 70.916 | — |
| SECONDARY 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 |
7; 0; 9; 36; 0; 1 | — |
| SECONDARY Parts A and B: Duration of Active Symptomatic Flare-up |
27.1; 39.5 | — |
| SECONDARY Part B: Change From Baseline in Whole Body Burden of HO at Months 12 and 24 |
28386; 193150 | — |
| SECONDARY Part B: Mean Percentage of Flare-ups Per Participant-Month Overall |
0.12 | — |
| SECONDARY Part C: Mean Percentage of Flare-ups Per Participant-Month Overall |
0.14 | — |
| SECONDARY Part C: Percentage of Participants With New HO at Months 12, 24, 36, 60, and 72 (Last Visit) |
60.0; 54.5; 61.5; 100.0; 86.2 | — |
Summary
Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by heterotopic ossification (HO), i.e., abnormal bone formation, often associated with painful, recurrent episodes of soft tissue swelling (flare-ups). Lesions begin in early childhood and lead to progressive ankyloses of major joints with resultant loss of movement.
In this study, the ability of different palovarotene dosing regimens to prevent the formation of new HO will be evaluated in adult and pediatric participants with FOP.
Eligibility Criteria
Inclusion Criteria
- Completion of Study PVO-1A-202/Part B.
- Written, signed, and dated informed consent and, for participants who are minors, age-appropriate participant assent (performed according to local regulations).
- Accessible for treatment with palovarotene and follow-up (able and willing to travel to a site for the initial and all follow-up clinic visits).
- Able to undergo low-dose, WBCT scan, excluding head.
- Females of child-bearing potential must have a negative blood or urine pregnancy test (with sensitivity of at least 50 mIU/mL) prior to administration of palovarotene.
- Male and FOCBP participants must agree to remain abstinent from heterosexual sex during treatment and for 1 month after treatment or, if sexually active, to use two effective methods of birth control during and for 1 month after treatment. Additionally, sexually active females of childbearing potential (FOCBP) participants must already be using two effective methods of birth control 1 month before treatment is to start. Specific risk of the use of retinoids during pregnancy, and the agreement to remain abstinent or use two effective methods of birth control will be clearly defined in the informed consent and the participant or legally authorized representatives.
Exclusion Criteria
- 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.
- Amylase or lipase >2x above the upper limit of normal or with a history of pancreatitis.
- Elevated aspartate aminotransferase or alanine aminotransferase >2.5x the upper limit of normal.
- Fasting triglycerides >400 mg/dL with or without therapy.
- Currently using vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, herbal preparations containing vitamin A or beta carotene, or fish oil, and unable or unwilling to discontinue use of these products during palovarotene treatment.
- Participants experiencing suicidal ideation (type 4 or 5) or any suicidal behavior within the past month as defined by the Columbia Suicide Severity Rating Scale (C-SSRS).
Data sourced from ClinicalTrials.gov (NCT02279095). 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.