A Study to Assess Safety, Tolerability and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP)

NCT05394116 | Active Not Recruiting Phase 3 DMC FDA Drug

• 3 other identifiers: R2477-FOP-21752022-000880-402023-508350-26-00
• Study Type: interventional
• Target: 63
• Locations: 18 countries
• Sites: 22

Brief Summary

This study is researching an experimental drug called garetosmab. The study is focused on adult patients with fibrodysplasia ossificans progressiva (FOP). The aim of the study is to see how safe and effective the study drug is in patients with FOP. The study is looking at several other research questions, including:

• What side effects may happen from receiving 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 drug less effective or could lead to side effects)

Conditions

Fibrodysplasia Ossificans Progressiva

Keywords

Heterotopic Ossification (HO) Lesions; Type I activin A receptor (ACVR1); Optima; LUMINA-1; Flare-Ups

Outcome Measures

Primary Outcomes (2)

• Number of new HO lesions

  At Week 56

• Incidence and severity of treatment-emergent adverse events of special interest (AESIs)

  Baseline to Week 56

Secondary Outcomes (16)

• Number of clinician-assessed flare-ups

  Through Weeks 28, 56 and 84

• Occurrence of new HO lesions

  At Weeks 28, 56 and 84

• Total volume of new HO lesions

  At Weeks 28, 56 and 84

• Occurrence of patient-reported flare-ups

  Through Weeks 28 and 56

• Number of new HO lesions

  At week 28 and 84

Study Arms (3)

High dose Garetosmab

EXPERIMENTAL

Garetosmab is administered by intravenous (IV) administration every 4 weeks (Q4W)

Drug: Garetosmab

Low dose Garetosmab

EXPERIMENTAL

Garetosmab is administered by IV administration Q4W

Drug: Garetosmab

Placebo

EXPERIMENTAL

Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV Q4W.

Drug: Placebo

Interventions

Garetosmab DRUG

Garetosmab is supplied as a liquid drug product and will be administered IV.

Also known as: REGN2477

High dose Garetosmab; Low dose Garetosmab

Placebo DRUG

Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV.

Placebo

Eligibility Criteria

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

You may qualify if:

• Clinical diagnosis of Fibrodysplasia Ossificans Progressiva (FOP) \[(based on findings of congenital malformation of the great toes, episodic soft tissue swelling, and/or progressive Heterotopic Ossification (HO)\]
• Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation
• FOP disease activity within 1 year of screening visit. FOP disease activity is defined as pain, swelling, stiffness, or other signs and symptoms associated with FOP flare-ups; or worsening of joint function, or radiographic progression of HO lesions (increase in size or number of HO lesions) with/without being associated with flare-up episodes
• Willing and able to undergo CT imaging procedures and other procedures as defined in the protocol

You may not qualify if:

• Cumulative Analog Joint Involvement Scale (CAJIS) score at screening \>19
• Participant has significant concomitant illness or history of significant illness such as but not limited to cardiac, renal, rheumatologic, neurologic, psychiatric, endocrine, metabolic, or lymphatic disease, that in the opinion of the study investigator might confound the results of the study or pose additional risk to the patient by their participation in the study
• Previous history or diagnosis of cancer
• Severely impaired renal function defined as estimated glomerular filtration rate \<30 milliliter per minute (mL/min) (/1.73 m\^2 calculated by the Modification of Diet in Renal Disease equation
• Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) \>9% at screening
• History of poorly controlled hypertension, as defined by:
• Systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg at the screening visit
• Systolic blood pressure of 160 mm Hg to 179 mm Hg or diastolic blood pressure of 100 mm Hg to 10\^9 mm Hg at the screening visit, AND a history of end-organ damage (including history of left-ventricular hypertrophy, heart failure, angina, myocardial infarction, stroke, transient ischemic attack, peripheral arterial disease, end-stage renal disease, and moderate-to-advanced retinopathy
• Known history of cerebral vascular malformation
• Cardiovascular conditions such as New York Heart Association class III or IV heart failure, cardiomyopathy, intermittent claudication, myocardial infarction, or acute coronary syndrome within 6 months prior to screening; symptomatic ventricular cardiac arrhythmia
• History of severe respiratory compromise requiring oxygen, respiratory support (eg, bilevel positive airway pressure \[biPAP\] or continuous positive airway pressure \[CPAP\]), or a history of aspiration pneumonia requiring hospitalization
• Prior use in the past year and concomitant use of bisphosphonates
• Concurrent participation in another interventional clinical study or a non-interventional study with radiographic measures or invasive procedures (eg, collection of blood or tissue samples)
• Treatment with another investigational drug, denosumab, imatinib or isotretinoin in the last 30 days or within 5 half-lives of the investigational drug, whichever is longer
• Pregnant or breastfeeding women

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (22)

University of California Los Angeles (UCLA) Medical Center

Los Angeles, California, 90095, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

Location

Hospital Israelita Albert Einstein

São Paulo, 05652-900, Brazil

Location

Universidad de Concepcion

Concepción, Bio Bio, 4030000, Chile

Location

Tongji Hospital of Tongji University

Shanghai, 200065, China

Location

Clinica Universidad de La Sabana

Chía, Cundinamarca, 140013, Colombia

Location

HUS Children and Adolescents Park Hospital Clinical Trial Unit

Helsinki, Stenbäckinkatu 11, 00029, Finland

Location

Hôpital Lapeyronie

Montpellier, 34090, France

Location

Hopital Lariboisiere

Paris, 75010, France

Location

Queen Mary Hospital

Hong Kong, 22553838, Hong Kong

Location

IRCCS Istituto Giannina Gaslini

Genoa, 16147, Italy

Location

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

Oita University Hospital

Yufu, Oita Prefecture, 879-5593, Japan

Location

Kyushu University Hospital

Fukuoka, 812-8582, Japan

Location

Hospital Kuala Lampur

Kuala Lumpur, 50586, Malaysia

Location

Amsterdam University Medical Center

Amsterdam, North Holland, 1081 HV, Netherlands

Location

Szpital Centrum Medyczne Medyk

Rzeszów, Podkarpackie Voivodeship, 35-326, Poland

Location

University of Cape Town

Rondebosch, Cape Town, 7700, South Africa

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Royal National Orthropaedic Hospital NHS Trust

Middlesex, Greater London, HA7 4LP, United Kingdom

Location

MeSH Terms

Conditions

Myositis Ossificans; Ossification, Heterotopic

Condition Hierarchy (Ancestors)

Myositis; Muscular Diseases; Musculoskeletal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Clinical Trial Management

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 4, 2022
• First Posted: May 27, 2022
• Study Start: November 21, 2022
• Primary Completion: July 17, 2025
• Study Completion (Estimated): February 27, 2029
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• 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
• 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

Locations

ES (1); CN (1); BR (1); KR (1); JP (3); CL (1); AU (1); US (2); GB (1); CO (1); ZA (1); HK (1); FR (2); FI (1); IT (1); MY (1); PL (1); NL (1)