Following the planned FALKON Part A primary analysis, the study did not meet its primary endpoint of reducing heterotopic ossification (HO) volume compared with placebo and met predefined futility criteria.

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 ).

Note on Primary Completion Date and Results Disclosure:

The Primary Completion Date (PCD) reflects the date when data collection is completed for all primary outcomes, as defined in the Final Rule (42 CFR Part 11). In this study, safety outcomes are designated as primary and collected through the end of study.

Therefore the PCD has been updated to align with this definition. The interim analyses will proceed per the protocol and SAP. Results will be disclosed in line with applicable regulatory timelines.

Key Inclusion Criteria:

• 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.

  1. Washout period for palovarotene is 30 days
  2. 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)

Key Exclusion Criteria:

• 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

Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, annotated case report form, statistical analysis plan, and dataset specifications.

Patient level data will be anonymized and study documents will be redacted to protect the privacy of study participants.

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.

Further details on Ipsen's sharing criteria and process for sharing are available here (https://www.ipsen.com/science/clinical-trials/clinical-data-transparency/).