Fibrodysplasia Ossificans ProgressivaPhase 3OPTIMANCT05394116
A Study to Assess Safety, Tolerability and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP)
A Phase 3 study testing Garetosmab in people with Fibrodysplasia Ossificans Progressiva, run by Regeneron Pharmaceuticals at 22 sites in 18 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fibrodysplasia Ossificans Progressiva
- What is being tested?
- Garetosmab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 63 participants
- Where
- 22 sitesin 18 countries
- Study dates
- 21 Nov 2022to 27 Feb 2029
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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:
Show all 18Show fewer
- 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
- Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception, as defined in the protocol
- 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
Trial locations and contacts
22 sites in 18 countries.
22 sites in 18 countries
Japan3 sites
Kyushu University Hospital
Fukuoka, 812-8582
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560
Oita University Hospital
Yufu, Oita Prefecture, 879-5593
United States2 sites
University of California Los Angeles (UCLA) Medical Center
Los Angeles, California, 90095
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
France2 sites
Hôpital Lapeyronie
Montpellier, 34090
Hopital Lariboisiere
Paris, 75010
Australia1 site
Royal North Shore Hospital
St Leonards, New South Wales, 2065
Finland1 site
HUS Children and Adolescents Park Hospital Clinical Trial Unit
Helsinki, Stenbäckinkatu 11, 00029
Netherlands1 site
Amsterdam University Medical Center
Amsterdam, North Holland, 1081 HV
Poland1 site
Szpital Centrum Medyczne Medyk
Rzeszów, Podkarpackie Voivodeship, 35-326
United Kingdom1 site
Royal National Orthropaedic Hospital NHS Trust
Middlesex, Greater London, HA7 4LP
About this study
Official title: 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)
- Conditions
- Fibrodysplasia Ossificans Progressiva
- Being tested
- Garetosmab, Placebo
- Keywords
- Heterotopic Ossification (HO) Lesions, Type I activin A receptor (ACVR1), Optima, LUMINA-1, Flare-Ups
- Medical subject headings
- Myositis Ossificans, Ossification, Heterotopic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GaretosmabDrug
Also called REGN2477
Garetosmab is supplied as a liquid drug product and will be administered IV.
PlaceboDrug
Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV.
| Study group | Role | What they receive |
|---|---|---|
| High dose Garetosmab | Experimental | Garetosmab is administered by intravenous (IV) administration every 4 weeks (Q4W) Receives: Drug: Garetosmab |
| Low dose Garetosmab | Experimental | Garetosmab is administered by IV administration Q4W Receives: 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of new HO lesions
Measured: At Week 56
Incidence and severity of treatment-emergent adverse events of special interest (AESIs)
Measured: Baseline to Week 56
Secondary outcomes (16)
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
Measured: Through Weeks 28, 56 and 84
Occurrence of new HO lesions
Reported as Yes/No
Week 84 Only for Patients on Extended Treatment
Measured: At Weeks 28, 56 and 84
Total volume of new HO lesions
Week 84 Only for Patients on Extended Treatment
Measured: At Weeks 28, 56 and 84
Occurrence of patient-reported flare-ups
Reported as Yes/No
Measured: Through Weeks 28 and 56
Number of new HO lesions
Week 84 Only for Patients on Extended Treatment
Measured: At week 28 and 84
Occurrence of clinician-assessed flare-ups
Reported as Yes/No
Week 84 Only for Patients on Extended Treatment
Measured: Through Weeks 28, 56 and 84
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.
Measured: Through Weeks 28 and 56
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
Measured: 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.
Measured: 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
Measured: 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
Measured: 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
Measured: At Weeks 28 and 56
Concentration of total activin A in serum over time
Measured: Through Week 56
Concentration of garetosmab in serum over time
Measured: Through Week 56
Incidence of anti-drug antibodies (ADA) to garetosmab over time
Measured: Through Week 56
Titer of ADA to garetosmab over time
Measured: Through Week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2022
- Study start21 Nov 2022
- Primary completion17 Jul 2025
- Study completion27 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Fibrodysplasia Ossificans ProgressivaStudies of the same condition, open and under way.
- More trials run by Regeneron PharmaceuticalsThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- Regeneron Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Trial Management, Study director, Regeneron Pharmaceuticals
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05394116
- Sponsor's protocol ID
- R2477-FOP-2175
- Other IDs
- 2022-000880-40, 2023-508350-26-00, 2023
- Acronym
- OPTIMA
- Status last verified
- Apr 2026
- First submitted
- 4 May 2022
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
- Expanded access
- Available
Publications
Papa R, Rhee S, Delai P, Zhang K, Balcazar IB, Rethanavelu K, Fujiwara T, Mishima K, Tabarkiewicz J, Funck-Brentano T, Stander R, Bachiller-Corral J, Dahir KM, Eekhoff EMW, Hero M, Kuong E, Uemura N, Zhou M, Trotter DG, Gu J, Sanchez RJ, O'Donovan DO, Economides AN, Pordy R, Hirshberg B, Yancopoulos GD, Keen R; OPTIMA Study Group. Efficacy and safety of garetosmab, an activin A-blocking antibody, in fibrodysplasia ossificans progressiva (OPTIMA): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2026 Sep 28:S0140-6736(26)01599-0. doi: 10.1016/S0140-6736(26)01599-0. Online ahead of print.
PubMed 42805227