fibrodysplasia ossificans progressiva (FOP) MedDRA version: 20.0 Level: PT Classification code 10068715 Term: Fibrodysplasia ossificans progressiva System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: IPN60130 10 mg capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Not yet available
Current Sponsor code: IPN60130
Other descriptive name: (R)-tetrahydrofuran-3-yl 4-(6-(5-
Sponsors
Clementia Pharmaceuticals Inc, an Ipsen Company
Eligibility
Sex/Gender
All
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 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 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 must already be using tw
Exclusion criteria
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 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Evaluate the efficacy of IPN60130 monotherapy compared with placebo recipients in inhibiting new heterotopic ossification (HO) volume in adult and paediatric participants with FOP as assessed by low-dose whole body computed tomography (WBCT) (excluding the head) • Evaluate the safety of IPN60130 in adult and paediatric participants with FOP ;Secondary Objective: • Change in HO volume of new HO lesions over time by WBCT at M12. • Number of new HO lesions by WBCT at M12. • Rate and number of flare-up days at M12. • The number of body regions with new HO at M12. • To evaluate the effect of IPN60130 on pain intensity over time at M12. • Proportion of participants with new HO by WBCT • Change in HO volume over time as detected by WBCT. Pharmacokinetic (PK) • From the PK interim analysis, to evaluate the plasma pharmacokinetics of low and high doses of IPN60130. • From the overall study, to evaluate the plasma PK of low and high doses of IPN60130. Exposure-Response •To evaluate the exposure-response relationship, if feasible. ;Primary end point(s): • 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, laboratory parameters, serum or urine pregnancy tests for females of childbearing potential (FOCBP), concomitant medications ;Timepoint(s) of evaluation of this end point: • WBCT: Pt A: D1, M6, M12; Pt B: M18, M24, ET • AEs/SAEs & Concomitant medications: Screening; at every participant contact • ECG & echocardiograms: Pt A: Screening, M1, M3, M6, M12; Pt B: M13, M15, M18, M24, ET • Cardiac biomarkers (inc. Troponin I (HS) & NT-proBNP): Pt A: Screening, D1, M1, M3, M6, M12; Pt B: M13, M15, M18, M24, ET • Vital Signs: Pt A: Screening, D1, M1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • 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. • Flare-up rate 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 <13 years of age for participants receiving IPN60130 compared with placebo recipients at M12 • The proportion of participants with any new HO in participants receiving IPN60130 compared with placebo recipients through M24. • Change from baseline in HO volume as detected by WBCT in participants receiving IPN60130 compared with placebo recipients and with participants receiving the standard of care in the NHS through M24. Pharmacokinetic • Pharmacokinetic parameters by population PK modelling using all sparse samples collected through Month 1 • Pharmacokinetic parameters by population PK modelling using all sparse samples collected during the study Exposure-Response • Exposure-response analysis by modelling using relevant efficacy and safety parameters ;Timepoint(s) of evaluation of this end point: As per E.5.1.1 and additionally; NRS and FPS: Pt A: D1, M1 - M12 ; Pt B: M13 - M24 PK: Pt A: D1, M1, M3, M6, M12; Pt B: M18, M24 | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, China, Colombia, France, Germany, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Portugal, Russian Federation, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactEric SOLIMAN
Clementia Pharmaceuticals Inc, an Ipsen Company
Outcome results
None listed