A Phase 2 study to assess the efficacy and safety of 2 dosage regimens of oral fidrisertib (IPN60130) for the treatment of fibrodysplasia ossificans progressiva in male and female paediatric and adult participants

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] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2020-002858-24-NL
• Lead Sponsor: Clementia Pharmaceuticals Inc, an Ipsen Company

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-09-08
• Last Update Posted: 8 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 98

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 will only be once safety in adult and older 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 relationsh

Exclusion Criteria

Participants are excluded from the study if any of the following criteria apply:

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 <50%.
3. Participants with severe mitral or tricuspid regurgitation on echocardiograph at screening.
4. Participants with significant underlying lung disease requiring supplementary oxygen or forced vital capacity <35% of predicted at screening.
5. Participants with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease as judged by the investigator.
6. Participants with severe hepatic impairment.

Prior/Concomitant Therapy
7. Concomitant medications that are strong inhibitors (including grapefruit juice) or inducers (including St John’s Wort) of cytochrome P450 (CYP) 3A4 activity and strong inhibitors or inducers of CYP2C19 activity or kinase inhibitors such as imatinib.
8. Prior use in the past year and concomitant use of bisphosphonates for participants in the PET-CT substudy.

Prior/Concurrent Clinical Study Experience
9. Concurrent participation in another interventional clinical study, or a noninterventional study with radiographic measures or invasive procedures (e.g. collection of blood or tissue samples).

Other Exclusions
1. Amylase or lipase >2× the upper limit of normal (ULN) or with a history of chronic pancreatitis.
2. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5×ULN.
3. Participants with hematologic abnormalities:
• Hgb<10g/dL
• Platelets<75,000/mm3
• WBC<2000/mm3
• Participants with coagulation test (prothrombin time [PT]/ international normalised ratio [INR], and activated partial thromboplastin time [aPTT]) measurements outside of the normal range at screening.
4. Female participants who are breastfeeding.
5. 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
Individuals with disqualifying laboratory abnormalities may be rescreened once within the screening window. Rescreening may be repeated more than once if the results are atypical for the participant based on prior results from preceding year.

Study & Design

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