fibrodysplasia ossificans progressiva (FOP)
Conditions
Interventions
Study intervention for Part A will include 3 double-blind arms comprising
weight-based 120 or 60 mg IPN60130 once daily or placebo. The total duration of
Part A will be up to 13 months, consisting o
Sponsors
Ipsen Pharmaceuticals
Eligibility
Age
2 Years to 64 Years
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in the study only if all of the following criteria apply: Age - Main Study 1. Participants must be at least 5 years of age, to be confirmed (entry for younger paediatric participants =15 years of age has been established) at the time of signing the informed participant/parent consent and, for participants who are minors, age-appropriate assent. Age - [18F]NaF PET-CT Imaging Substudy 2. Participants must be at least 15 years of age at the time of signing the informed participant/parent consent for the main study and, for participants who are minors, age-appropriate assent. Type of Participant and Disease Characteristics 3. Participants must be clinically diagnosed with FOP, with the R206H ACVR1 mutation or other FOP variants associated with progressive HO. 4. Participants must have at least one flare-up in the preceding year of the screening visit. 5. Participants who have participated in a prior clinical study using another investigational product for the treatment of FOP may be enrolled after a washout of at least 5 half-lives of the other investigational product. Participants with prior treatment such as, but not limited to, imatinib, isotretinoin, or palovarotene may be enrolled 30 days after discontinuation or after washout of at least 5 half-lives, whichever is longer. 6. Participants must be able to perform pulmonary function tests as defined in the protocol adequately and reliably. 7. Participants must be able to have an adequate echocardiography assessment at screening for evaluation of left ventricular structure and function as defined by the protocol. 8. Participants must be accessible for treatment and follow-up and be able to undergo all study procedures. Participants 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. Participants must be able to undergo low-dose WBCT (excluding head) without sedation. Weight 9. Body weight >=10 kg. Sex 10.Male and/or female participants: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. a. Male participants: Male participants of childbearing potential must agree to remain abstinent from heterosexual sex during treatment and for 90 days after treatment or, if sexually active, to use two effective methods of birth control, one of which must be highly effective during and for 90 days after treatment. The agreement to remain abstinent or use two effective methods (one of which must be highly effective) of birth control will be clearly defined in the informed consent; the participant or legally authorized representatives (e.g. parents, caregivers, or legal guardians) must sign this specific section. b. Female participants: Females of childbearing potential (defined in Appendix 10.5.1) must have a negative blood or urine pregnancy test (with sensitivity of at least 50 mIU/mL) prior to administration of study drug. 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, one of which must be highly effective during and for 1 month after treatment. Additionally, sexually active FOCBP participants in a heterosexual relationship m
Exclusion criteria
Exclusion criteria: Medical Conditions 1. Participants with complete heart block and left bundle branch block on screening electrocardiogram. 2. Participants with screening echocardiograph showing septal or left ventricular free wall thickness >12 mm for adult participants or a z-score >3 compared with population norms for children and adolescent participants or LVEF 2× the upper limit of normal (ULN) or with a history of chronic pancreatitis. 11. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5×ULN. 12. Participants with hematologic abnormalities: • Hgb
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary End Point • The annualized change from baseline in HO volume as assessed by low-dose WBCT (excluding the head) in treated participants receiving IPN60130 through M12 compared with placebo • Adverse events / serious adverse events (AEs/SAE), cardiac outcomes (electrocardiogram (ECG), echocardiograms, cardiac biomarkers), vital signs, physical examinations, body weight and height, eye exams, laboratory parameters, serum or urine pregnancy tests for females of childbearing potential (FOCBP), concomitant medications | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary End Point • Change from baseline in HO volume of new HO lesions as detected by WBCT in participants receiving IPN60130 compared with placebo recipient at M12. • Change from baseline in number of HO lesions by WBCT in participants receiving IPN60130 compared with placebo recipients at M12. • Rate of flare-up (as confirmed by Investigator evaluation) and number of flare-up days in participants receiving INP60130 compared with placebo at M12 • The number of body regions with new HO in participants treated with IPN60130 compared with placebo recipients at M12 • Change from baseline in pain intensity over time assessed using the NRS in participants >=13 years of age and the Wong Baker FPS in participants | — |
Countries
Netherlands
Outcome results
None listed