A Study to Assess the Effectiveness and Safety of 2 Dosage Regimens of Oral Fidrisertib (IPN60130) for the Treatment of Fibrodysplasia Ossificans Progressiva (FOP).

NCT05039515 | Terminated Phase 2 DMC FDA Drug

• 3 other identifiers: D-CA-60130-4522020-002858-242024-511469-13-00
• Study Type: interventional
• Target: 113
• Locations: 14 countries
• Sites: 25

Brief Summary

Fibrodysplasia Ossificans Progressiva (FOP) is a rare, severely disabling disease characterized by the presence of bone in soft tissue where bone normally does not exist, known as Heterotopic Ossification (HO). It is often associated with painful, recurrent episodes of soft tissue swelling (flare-ups) that lead to abnormal stiffening and immobility (ankyloses) of major joints with cumulative and irreversible loss of movement and disability. This study will evaluate the efficacy of 2 dosing regimens of IPN60130 in inhibiting new HO volume compared with placebo (a dummy treatment) in adult and paediatric participants with FOP. It will be assessed by a scan (provides internal images of the body) called low dose Whole Body Computed Tomography (WBCT), excluding head. Adults and participants 5 years of age or older are also eligible for a sub study to evaluate HO lesions assessed by another type of scan, Fluorine-18-labelled natrium fluoride Positron Emission Tomography-Computed Tomography (\[18F\]NaF PET-CT ).

Conditions

Fibrodysplasia Ossificans Progressiva

Outcome Measures

Primary Outcomes (6)

• Annualized change in HO volume as assessed by low-dose WBCT (excluding the head) in treated participants receiving IPN60130 compared with placebo.

  From baseline to 12 months

• Incidence of Adverse Events / Serious Adverse Events (AEs/SAE)

  From baseline until the end of study (63 months)

• Change from baseline in clinically significant abnormal values in laboratory parameters (haematology, biochemistry, and urinalysis)

  Percentage of participants with clinically significant change in laboratory parameters (biochemistry, hematology and urinalysis) will be reported. The clinical significance will be graded by the investigator.

  From baseline until the end of study (63 months)

• Change from baseline in physical examination findings

  Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be graded by the investigator.

  From baseline until the end of study (63 months)

• Change from baseline in clinically significant vital signs

  Percentage of participants with clinically significant changes in Vital Signs will be reported. The clinical significance will be graded by the investigator.

  From baseline until the end of study (63 months)

• Change from baseline in clinically significant Electrocardiogram (ECG) readings

  Percentage of participants with clinically significant changes in ECG readings will be reported. The clinical significance will be graded by the investigator.

  From baseline until the end of study (63 months)

Secondary Outcomes (14)

• Change in HO volume of new HO lesions as detected by WBCT in participants receiving IPN60130 compared with placebo recipients

  From baseline up to 12 months

• Change in number of HO lesions by WBCT in participants receiving IPN60130 compared with placebo recipients

  From baseline up to 12 months

• Flare-up rate and number of flare-up days in participants receiving IPN60130 compared with placebo recipients

  From baseline up to 12 months

• The number of body regions with new HO in participants receiving IPN60130 compared with placebo recipients

  From baseline up to 12 months

• Change in pain intensity

  From baseline up to 12 months

Study Arms (3)

IPN60130 high dosage

EXPERIMENTAL

Oral capsule, swallowed whole or sprinkled onto food, once daily

Drug: IPN60130

IPN60130 low dosage

EXPERIMENTAL

Oral capsule, swallowed whole or sprinkled onto food, once daily

Drug: IPN60130

Placebo

PLACEBO COMPARATOR

Oral capsule, swallowed whole or sprinkled onto food, once daily

Drug: Placebo

Interventions

Placebo DRUG

Placebo will be supplied as powder filled hard capsules

Placebo

IPN60130 DRUG

Immediate-release capsule containing high dose of the drug substance.

Also known as: Fidrisertib

IPN60130 high dosage

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• Participants must be clinically diagnosed with FOP, with the R206H ACVR1 mutation or other FOP variants associated with progressive HO.
• Participants must have disease progression in the preceding year of the screening visit.
• 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.
• Washout period for palovarotene is 30 days
• Washout period for garetosmab is 4 months
• Participants must be able to perform pulmonary function tests adequately and reliably.
• 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.
• 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.
• Body weight ≥10 kg.
• Abstinent or using two highly effective forms of birth control. Females must also have a negative blood or urine pregnancy test prior to administration of study drug.
• 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)

You may not qualify if:

• Participants with complete heart block and left bundle branch block on screening electrocardiogram.
• Participants with screening echocardiography 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 left ventricular ejection fraction (LVEF) \<50%.
• Participants with severe mitral or tricuspid regurgitation on echocardiography at screening.
• Participants with significant underlying lung disease requiring supplementary oxygen or forced vital capacity \<35% of predicted at screening.
• Participants with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or another significant disease as judged by the investigator.
• Participants with severe hepatic impairment.
• Concomitant medications that are strong inhibitors (including grapefruit juice) or inducers (including St John's Wort) of cytochrome P450 (CYP) 3A4 activity; or kinase inhibitors such as imatinib.
• Prior use in the past year and concomitant use of bisphosphonates for participants in the PET-CT sub study.
• 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).
• Amylase or lipase \>2× the upper limit of normal (ULN) or with a history of chronic pancreatitis.
• Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5×ULN.
• Participants with hematologic abnormalities:
• Hgb\<10g/dL
• Platelets\<75,000/mm3
• WBC\<2000/mm3

Sponsors & Collaborators

• Clementia Pharmaceuticals Inc.: lead
• Ipsen: collaborator

Study Sites (25)

University of California San Francisco (UCSF)

San Francisco, California, 94143, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

The Perelman School of Medicine - The University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Hospital Italiano de Buenos Aires

Buenos Aires, Argentina

Location

Royal North Shore Hospital - New South Wales

Sydney, Australia

Location

University Hospitals Leuven

Leuven, Belgium

Location

University of Alberta, Alberta Health Services (AHS)

Edmonton, Canada

Location

University Health Network (UHN), Toronto General Hospital (TGH)

Toronto, Canada

Location

Children's Hospital Capital Institute of Pediatrics (CIP)

Beijing, China

Location

Peking Union Medical College Hospital

Beijing, China

Location

Shangai Children Medical Center

Shanghai, China

Location

Tongi University - Tongi Hospital

Shanghai, China

Location

Groupe Hospitalier Necker Enfants Malades

Paris, 75015, France

Location

Hopital Lariboisiere

Paris, France

Location

Irccs Gaslini Institute

Genoa, 16147, Italy

Location

Nagoya University Hospital

Nagoya, Japan

Location

Aichi Children's Health and Medical Center

Ōbu, Japan

Location

The University of Tokyo Hospital

Tokyo, Japan

Location

Instituto Nacional De Rehabilitacion

Mexico City, Mexico

Location

Hospital Center Lisbon North, E.P.E- Hospital Santa Maria

Lisbon, Portugal

Location

Seoul National University Hospital

Seoul, South Korea

Location

Hospital Universitario Ramon y Cajal

Pozuelo de Alarcón, 28224, Spain

Location

Hospital Universitario Y Politecnico La Femerge

Valencia, 46026, Spain

Location

Norrlands Universitetssjukhus

Umeå, Sweden

Location

MeSH Terms

Conditions

Myositis Ossificans

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases

Study Officials

• Ipsen Medical Director

  Ipsen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 2, 2021
• First Posted: September 9, 2021
• Study Start: December 1, 2021
• Primary Completion: March 27, 2026
• Study Completion: March 27, 2026
• Last Updated: April 24, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Time Frame: Where applicable, data from eligible studies are available 6 months after the studied medicine and indication have been approved in the US and/or EU.
• Access Criteria: Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).

Locations

SE (1); AU (1); US (4); ME (1); PT (1); CN (4); BE (1); IT (1); AR (1); CA (2); JP (3); FR (2); KR (1); ES (2)