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

Phase 3 Randomized, Placebo-Controlled Study to Assess Safety, Tolerability, and Efficacy of Garetosmab in Patients With Fibrodysplasia Ossificans Progressiva

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)

Study Overview

• Status: Active, not recruiting
• Conditions: Fibrodysplasia Ossificans Progressiva
• Intervention / Treatment: Drug: Garetosmab; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 3

Expanded Access

Temporarily not available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • St Leonards, New South Wales, Australia, 2065
      • Royal North Shore Hospital
• Brazil
  • São Paulo, Brazil, 05652-900
    • Hospital Israelita Albert Einstein
• Chile
  • Bio Bio
    • Concepción, Bio Bio, Chile, 4030000
      • Universidad de Concepcion
• China
  • Shanghai, China, 200065
    • Tongji Hospital of Tongji University
• Colombia
  • Cundinamarca
    • Chía, Cundinamarca, Colombia, 140013
      • Clínica Universidad de La Sabana
• Finland
  • Stenbäckinkatu 11
    • Helsinki, Stenbäckinkatu 11, Finland, 00029
      • HUS Children and Adolescents Park Hospital Clinical Trial Unit
• France
  • Montpellier, France, 34090
    • Hopital Lapeyronie
  • Paris, France, 75010
    • Hôpital Lariboisière
• Hong Kong
  • Hong Kong, Hong Kong, 22553838
    • Queen Mary Hospital
• Italy
  • Genoa, Italy, 16147
    • IRCCS Istituto Giannina Gaslini
• Japan
  • Fukuoka, Japan, 812-8582
    • Kyushu University Hospital
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 466-8560
      • Nagoya University Hospital
  • Oita Prefecture
    • Yufu, Oita Prefecture, Japan, 879-5593
      • Oita University Hospital
• Malaysia
  • Kuala Lumpur, Malaysia, 50586
    • Hospital Kuala Lampur
• Netherlands
  • North Holland
    • Amsterdam, North Holland, Netherlands, 1081 HV
      • Amsterdam University Medical Center
• Poland
  • Podkarpackie Voivodeship
    • Rzeszów, Podkarpackie Voivodeship, Poland, 35-326
      • Szpital Centrum Medyczne Medyk
• South Africa
  • Cape Town
    • Rondebosch, Cape Town, South Africa, 7700
      • University of Cape Town
• South Korea
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
• Spain
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
• United Kingdom
  • Greater London
    • Middlesex, Greater London, United Kingdom, HA7 4LP
      • Royal National Orthropaedic Hospital NHS Trust
• United States
  • California
    • Los Angeles, California, United States, 90095
      • University of California Los Angeles (UCLA) Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. 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)]
2. Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation
3. 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
4. Willing and able to undergo CT imaging procedures and other procedures as defined in the protocol

Key Exclusion Criteria:

1. Cumulative Analog Joint Involvement Scale (CAJIS) score at screening >19
2. 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
3. Previous history or diagnosis of cancer
4. 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
5. Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) >9% at screening

6. History of poorly controlled hypertension, as defined by:

   1. Systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg at the screening visit
   2. 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
7. Known history of cerebral vascular malformation
8. 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
9. 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
10. Prior use in the past year and concomitant use of bisphosphonates
11. 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)
12. 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
13. Pregnant or breastfeeding women
14. Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception, as defined in the protocol
15. Male patients with WOCBP partners who are not willing to use condoms with WOCBP partners to prevent potential fetal exposure, as defined in the protocol

Note: Other protocol defined Inclusion/Exclusion Criteria apply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High dose Garetosmab; Garetosmab is administered by intravenous (IV) administration every 4 weeks (Q4W)	Drug: Garetosmab; Garetosmab is supplied as a liquid drug product and will be administered IV.; Other Names: REGN2477
Experimental: Low dose Garetosmab; Garetosmab is administered by IV administration Q4W	Drug: Garetosmab; Garetosmab is supplied as a liquid drug product and will be administered IV.; Other Names: REGN2477
Experimental: Placebo; Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV Q4W.	Drug: Placebo; Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence and severity of treatment-emergent adverse events of special interest (AESIs)	Baseline to Week 56
Number of new HO lesions	At Week 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of patient-reported flare-ups	Flare-up is defined as two or more of the following: pain, swelling, joint stiffness, or decrease in movement. The FOP flare-up dairy is a questionnaire and is self-completed by the participant daily.	Through Weeks 28 and 56
Occurrence of patient-reported flare-ups	Reported as Yes/No	Through Weeks 28 and 56
Concentration of total activin A in serum over time		Through Week 56
Incidence of anti-drug antibodies (ADA) to garetosmab over time		Through Week 56
Titer of ADA to garetosmab over time		Through Week 56
Concentration of garetosmab in serum over time		Through Week 56
Number of clinician-assessed flare-ups	Investigator assess flare-up events according to his/her medical judgment. A FOP flare-up is characterized as episodic, painful inflammatory soft tissue swelling. Week 84 Only for Patients on Extended Treatment	Through Weeks 28, 56 and 84
Occurrence of new HO lesions	Reported as Yes/No Week 84 Only for Patients on Extended Treatment	At Weeks 28, 56 and 84
Total volume of new HO lesions	Week 84 Only for Patients on Extended Treatment	At Weeks 28, 56 and 84
Number of new HO lesions	Week 84 Only for Patients on Extended Treatment	At week 28 and 84
Occurrence of clinician-assessed flare-ups	Reported as Yes/No Week 84 Only for Patients on Extended Treatment	Through Weeks 28, 56 and 84
Change in joint function assessment by physician using cumulative analog joint involvement scale (CAJIS)	CAJIS is a clinician assessment of 15 major joints; each major joint rated normal unaffected (0), affected (1), or completely functionally ankylosed (2). The total score ranges from 0 to 30	Baseline to Weeks 28 and 56
Change in pulmonary function as assessed by spirometry	Forced vital capacity (FVC) and Forced expiratory volume in 1 second (FEV1) and the ratio of FEV1/FVC will be determined by spirometry.	Baseline at Weeks 28 and 56
Change in disease severity as assessed by the Patient Global Impression of Severity (PGIS)	PGIS is a single item, self-administered questionnaire to assess the patient's global impression of severity	Baseline to Weeks 28 and 56
Change in disease severity as assessed by the Patient's Global Impression of Change (PGIC)	PGIC is a single item, self-administered questionnaire to assess the patient's global impression of change	At Weeks 28 and 56
Change in disease severity as assessed by the Clinician's Global Impression of Change (CGIC)	CGIC is a single-item questionnaire to assess the clinician's global impression of change	At Weeks 28 and 56

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Welcome to the OPTIMA Clinical Trial For people with fibrodysplasia ossificans progressiva

Study record dates

Study Major Dates

• Study Start (Actual): November 21, 2022
• Primary Completion (Actual): July 17, 2025
• Study Completion (Estimated): February 27, 2029

Study Registration Dates

• First Submitted: May 4, 2022
• First Submitted That Met QC Criteria: May 23, 2022
• First Posted (Actual): May 27, 2022

Study Record Updates

• Last Update Posted (Estimated): January 16, 2026
• Last Update Submitted That Met QC Criteria: January 15, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Heterotopic Ossification (HO) Lesions; Type I activin A receptor (ACVR1); Optima; LUMINA-1; Flare-Ups
• Additional Relevant MeSH Terms: Musculoskeletal Diseases; Muscular Diseases; Pathologic Processes; Myositis; Pathological Conditions, Signs and Symptoms; Myositis Ossificans; Ossification, Heterotopic
• Other Study ID Numbers: R2477-FOP-2175; 2022-000880-40 (Registry Identifier: EudraCT); 2023-508350-26-00 (Registry Identifier: CTIS (EU))

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