A study assessing the efficacy and safety of 2 dosage regimens of oral fidrisertib (IPN60130) for FOP

JRCT ID: jRCT2041220080

Registered date:26/10/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: fibrodysplasia ossificans progressiva
• Date of first enrollment: 10/11/2023
• Target sample size: 4
• Countries of recruitment: Argentina,Japan,Australia,Japan,Brazil,Japan,Columbia,Japan,Canada,Japan,China,Japan,France,Japan,Germany,Japan,Italy,Japan,Korea republic of,Japan,Mexico,Japan,Netherlands,Japan,Spain,Japan,Sweden,Japan,United Kingdom,Japan,United States,Japan,Belgium,Japan,Portugal,Japan
• Study type: Interventional

Intervention(s)

- fidrisertib high dosage arm
- fidrisertib low dosage arm
- Placebo arm
Oral capsule, swallowed whole or sprinkled onto food, once daily

Outcome(s)

Primary Outcome

'1.Annualized change in HO volume as assessed by low-dose WBCT (excluding the head) in treated participants receiving IPN60130 compared with placebo.
[Time Frame: From baseline to 12 months]
2.Incidence of Adverse Events / Serious Adverse Events (AEs/SAE)
[Time Frame: From baseline until the end of study (25 months)]

Key inclusion & exclusion criteria

• Age minimum: >= 5age old
• Age maximum: Not applicable
• Gender: Both

Include 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, ageappropriate 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 disease progression in the preceding year of the screening visit by having at least one of the following:
a. A self-reported flare-up with at least one major symptom of a flare-up, including swelling, pain (a new onset pain in a new site), decreased movement, stiffness, warmth, or redness
b. A new palpable HO
c. A new joint ankylosis
d. An increase in CAJIS score (if previous CAJIS assessment is available)
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, garetosmab, or palovarotene may be enrolled 30 days after discontinuation or after washout of at least 5 half-lives, whichever is longer.
a. Washout period for palovarotene is 30 days
b. Washout period for garetosmab is 4 months.
6. Participants must be able to perform pulmonary function tests 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 2 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 2 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 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 must already be using two effective methods of birth control (one of which must be highly effective) 1 month before treatment is to start.
Specific risks of study drug use during pregnancy as well as the agreement to remain abstinent or use two effective methods of birth control (one of which must be highly effective) 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.
Informed Consent
11. Participants must be capable of giving written, signed, and dated informed participant/parent consent; and for participants who are minors, age-appropriate assent and/or legal guardian consent (performed according to local regulations).

Exclude 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 Johns Wort) of cytochrome P450 (CYP) 3A4 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
10. Amylase or lipase >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<10g/dL
- Platelets<75,000/mm^3
- WBC<2000/mm^3
13. Female participants who are breastfeeding.
14. 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.

Related Information

• Primary Sponsor: Negar Karimian
• Secondary ID(s): 2020-002858-24