An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP)

• Register: ClinicalTrials.gov
• Last refreshed on: 24 October 2022
• Main ID: NCT02279095
• Date of registration: 26/10/2014
• Prospective Registration: Yes
• Primary sponsor: Clementia Pharmaceuticals Inc.
• Public title: An Open-Label Extension Study of Palovarotene Treatment in Fibrodysplasia Ossificans Progressiva (FOP)
• Scientific title: A Phase 2, Open-Label Extension, Efficacy and Safety Study of a Retinoic Acid Receptor Gamma (RAR?) Specific Agonist (Palovarotene) in the Treatment of Preosseous Flare-ups in Subjects With Fibrodysplasia Ossificans Progressiva (FOP)
• Date of first enrolment: October 27, 2014
• Target sample size: 54
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02279095
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Argentina, Australia, France, United Kingdom, United States

Contacts

• Name: Ipsen Medical Director
• Affiliation: Ipsen

Key inclusion & exclusion 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).



Age minimum: 6 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Fibrodysplasia Ossificans Progressiva

Intervention(s)

Drug: Palovarotene dose level 4

Drug: Palovarotene dose level 2

Drug: Palovarotene dose level 1

Drug: Palovarotene dose level 3

Primary Outcome(s)

Part A and Part B - Proportion of flare-up with no new HO ("responders") [Time Frame: Week 12]

Part C - Annualized change in new HO volume [Time Frame: Every 12 months for up to 72 months]

Secondary Outcome(s)

Duration of active, symptomatic flare-up (start date and end date) [Time Frame: Up to 12 weeks]

Part A - Change from baseline in cartilage, bone, angiogenesis, and inflammation biomarkers [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 2, 4, 6, and 12 (Flare-up Component)]

Part A and Part B - Change from baseline in physical and mental health [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 2, 4, 6, 8, 9, and 12 (Flare-up Component)]

Part A and Part B - Change from baseline in ROM [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 6 and 12 (Flare-up Component)]

Part A - Proportion of participants across the seven HO scores (0-6) [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 6 and 12 (Flare-up Component)]

Part A and Part B - Participant and Investigator global assessment of movement [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 6 and 12 (Flare-up Component)]

Part B (Chronic treatment) - Number of flare-ups per participant-month overall, and by edema severity [Time Frame: Up to 24 months]

Part B - Change from baseline in amount of bone formation (volume) [Time Frame: Flare-up Week 12]

Part C - Change from baseline in physical and mental function for participants =15 years old and mental function for participants <15 years old [Time Frame: Every 6 months up to 72 months]

Part C - Percent of participants with new HO [Time Frame: Every 12 months up to 72 months]

Part B (Chronic treatment) - Change from baseline in whole body burden of HO [Time Frame: Study Months 12 and 24]

Part A and Part B - Change from baseline in the use of assistive devices and adaptations for daily living by FOP participants [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 6 and 12 (Flare-up Component)]

Part C - Change from baseline in ROM [Time Frame: Every 6 months up to 72 months]

Part A - Change from baseline in amount (area) of new heterotopic bone formed [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 6 and 12 (Flare-up Component)]

Part A - Change from baseline in pain and swelling (for participants under 8 years of age) [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 2, 4, 6, 9, and 12 (Flare-up Component)]

Part A and Part B - Change from baseline in active range of motion (ROM) [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 6 and 12 (Flare-up Component)]

Part A and Part B - Change from baseline in physical function [Time Frame: Study Months 6 and 12 (Follow-up Component); Flare-up Weeks 2, 4, 6, 8, 9, and 12 (Flare-up Component)]

Part A and Part B - Presence of soft tissue swelling and/or cartilage [Time Frame: Flare-up Weeks 6 and 12 (Flare-up Component)]

Part B - Change from baseline in cartilage, bone, angiogenesis, and inflammation biomarkers [Time Frame: Flare-up Weeks 4, 8, and 12]

Part C - Change from baseline in physical function [Time Frame: Every 6 months up to 72 months]

Secondary ID(s)

PVO-1A-202

2014-002496-28

Source(s) of Monetary Support

Please refer to primary and secondary sponsors