A Study to Investigate the Safety, Pharmacokinetics (PK), and Efficacy of Garetosmab in Children and Adolescents With Fibrodysplasia Ossificans Progressiva (FOP) (OPTIMA-2)

Phase 3 Evaluation of the Safety, Pharmacokinetics, and Efficacy of Garetosmab (Anti-Activin A Monoclonal Antibody) in Children and Adolescents With Fibrodysplasia Ossificans Progressiva

This study is researching an experimental drug called garetosmab, referred to as "study drug". The study is focused on children and adolescent participants with FOP.

The aim of the study is to see how safe, tolerable, and effective the study drug is.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drug
• How much study drug is in the blood at different times
• Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects)

Study Overview

• Status: Not yet recruiting
• Conditions: Fibrodysplasia Ossificans Progressiva (FOP)
• Intervention / Treatment: Drug: garetosmab

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. For USA participants, age criteria are 4 to < 18 years old, at the time of the administration of the first dose of study intervention. Non-USA participants age criteria are 2 to < 18 years old
2. Must have a confirmation of FOP diagnosis, as described in the protocol

3. At the time of enrollment, participants must weight:

   1. Cohort 1 > 30 kg
   2. Cohort 2 > 30 kg
   3. Cohort 3 ≤ 30 kg

Key Exclusion Criteria:

1. Cumulative Analog Joint Involvement Scale (CAJIS) score > 19 at the time of screening
2. Participant has significant concomitant illness or history of significant illness, as described in the protocol
3. Previous history or diagnosis of cancer
4. Ongoing significant viral or bacterial illness, within 2 weeks of the first study drug administration
5. History of severe respiratory compromise requiring oxygen, respiratory support
6. Known history of cerebral vascular malformation
7. Participants with a history of severe, non-traumatic bleeding requiring transfusion or hospitalization for hemodynamic compromise
8. Participants with a known pre-existing medical history of a bleeding diathesis, as described in the protocol

NOTE: Other Protocol-defined Inclusion/Exclusion Criteria Apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: Adolescents	Drug: garetosmab; Administered per the protocol; Other Names: REGN2477
Experimental: Cohort 2: Children	Drug: garetosmab; Administered per the protocol; Other Names: REGN2477
Experimental: Cohort 3: Children and Adolescents	Drug: garetosmab; Administered per the protocol; Other Names: REGN2477

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Occurrence of Treatment-Emergent Adverse Event (TEAEs)	Baseline to week 28
Occurrence of TEAEs	Baseline to week 56
Severity of TEAEs	Baseline to week 28
Severity of TEAEs	Baseline to week 56
Concentrations of functional garetosmab in serum	Through week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total volume of new Heterotopic Ossification (HO) lesion		At week 28 and week 56
Number of new HO lesions		At week 28 and week 56
Occurrence of new HO lesions		At week 28 and week 56
Number of clinician-assessed flare-ups		Through week 28 and week 56
Occurrence of clinician-assessed flare-ups		Through week 28 and week 56
Number of patient/caregiver-reported flare-ups		Through Week 28 and week 56
Occurrence of patient/caregiver-reported flare-ups		Through week 28 and week 56
Change from baseline in Tanner puberty scale	Tanner puberty scale or stages: Staging of sexual development is graded on a 5-point ordinal scale ranging from 1 (prepubertal) to 5 (adultlike) for female breast development, male external genitals, and pubic hair	At week 28 and week 56
Characteristics of menstrual cycles for female participants who reached menarche		Over 28 weeks and 56 weeks
Height-for-age Z-Scores according to the World Health Organization (WHO) Growth Reference Data for Children	Participants 5-19 years of age Z-score represents standardized measure of how far an individual deviated from study cohort average at baseline. A higher Z-score reflects better performance.	Through week 56
Concentrations of total activin A in serum		Through week 56
Occurence of Anti-Drug Antibody (ADA) to garetosmab		Through week 56
Magnitude of ADA to garetosmab		Through week 56
Change from baseline in hearing function as assessed by audiometry		At week 28 and week 56
Change from baseline in Pediatric Quality of Life inventory (PedsQL) scores	Age-appropriate PedsQL Generic Core Scales will be used to measure HRQoL in children and adolescents. Response options include 5-point Likert scale (or 3-point Likert scale for the young children self-report) for each item asking about experience within the past week. Global scores are transformed to a 0 to 100 scale with higher scores indicating better quality of life.	At week 28 and week 56
Acceptability and tolerability assessment via exit interview	Each interview will be conducted by trained external interviewers following a semi-structured interview guide of questions for the participants about their overall experience in the trial.	Up to week 30

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): July 30, 2026
• Primary Completion (Estimated): December 10, 2028
• Study Completion (Estimated): December 21, 2029

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: April 22, 2026
• First Posted (Actual): April 30, 2026

Study Record Updates

• Last Update Posted (Actual): April 30, 2026
• Last Update Submitted That Met QC Criteria: April 22, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Type I Activin A Receptor (ACVR1) FOP-causing mutation
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Myositis; Myositis Ossificans
• Other Study ID Numbers: R2477-FOP-2413; 2024-518415-19-01 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No