A clinical trial to evaluate the Efficacy and Safety of Oral Palovarotene as a treatment for Fibrodysplasia Ossificans Progressiva (FOP)

Phase 1

• Conditions: Fibrodysplasia Ossificans Progressiva (FOP); MedDRA version: 20.0Level: PTClassification code 10068715Term: Fibrodysplasia ossificans progressivaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]

• Registration Number: EUCTR2017-002541-29-SE
• Lead Sponsor: Clementia Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-09-20
• Study Completion: 2022-09-07
• Last Update Posted: 4 September 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 107

Inclusion Criteria

Subjects must meet all of the following criteria to be eligible for enrollment:
1. Written, signed, and dated informed subject/parent consent; and for subjects who are minors, age-appropriate assent (performed according to local
regulations).
2. Male or female at least 4 years of age.
3. Previous participation in the NHS; or clinically diagnosed with FOP, with the R206H ACVR1 mutation or other FOP variants reported to be associated with progressive HO (who have not previously participated in any Clementia sponsored study); or participants in Study PVO 1A 202 or Study PVO-1A-204 who cannot currently receive the chronic/flare-up regimen due to country of residence or those traveling long distances to participate in the Phase 2 trial.
4. No flare-up symptoms within the past 4 weeks, including at the time of enrollment.
5. 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 subjects 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 FOCBP subjects 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 subject or legally authorized representatives (eg, parents, caregivers, or legal guardians) must specifically sign this section.
6. Must be accessible for treatment and follow-up, and be able to undergo all study procedures. Subjects living at distant locations from the investigational site must be able and willing to travel to a site for the initial and all on-site follow-up visits. Subjects must be able to undergo low-dose, WBCT (excluding head) without sedation.
Are the trial subjects under 18? yes
Number of subjects for this age range: 80
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 27
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects meeting any of the following criteria are not eligible for enrollment:
1. Weight <10 kg.
2. If currently using 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.
3. Exposure to synthetic oral retinoids other than palovarotene within 4 weeks prior to screening.
4. Concurrent treatment with tetracycline or any tetracycline derivatives due to the potential increased risk of pseudotumor cerebri.
5. History of allergy or hypersensitivity to retinoids, gelatin or lactose (note that lactose intolerance is not exclusionary).
6. Concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity; or kinase inhibitors such as
imatinib (see Section 5.2.1).
7. Amylase or lipase >2x above the upper limit of normal (ULN) or with a history of chronic pancreatitis.
8. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x ULN.
9. Fasting triglycerides >400 mg/dL with or without therapy.
10. Female subjects who are breastfeeding.
11. Subjects with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic,
psychiatric, or other significant disease.
12. Subjects 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).
13. Simultaneous participation in another interventional clinical research study (other than palovarotene studies) within 4 weeks prior to Screening; or within five half-lives of the investigational agent,
whichever is longer.
14. Any reason that, in the opinion of the Investigator, would lead to the inability of the subject and/or family to comply with the protocol.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified