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

Fibrodysplasia Ossificans Progressiva Clinical Trial

— OPTIMA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05394116
• Other study ID #: R2477-FOP-2175
• Secondary ID: 2022-000880-40
• Status: Recruiting
• Phase: Phase 3
• Start date: November 21, 2022
• Est. completion date: June 12, 2026

Study information

• Verified date: January 2024
• Source: Regeneron Pharmaceuticals
• Contact: Clinical Trials Administrator
• Phone: 844-734-6643
• Email: clinicaltrials[@]regeneron.com
• Is FDA regulated: No
• Study type: Interventional

Clinical 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. 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 your 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)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 66
• Est. completion date: June 12, 2026
• Est. primary completion date: April 10, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 109 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

Related Conditions & MeSH terms

• Fibrodysplasia Ossificans Progressiva

Intervention

Drug:
• Garetosmab
Garetosmab is supplied as a liquid drug product and will be administered IV.
• Placebo
Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV.

Locations

Country	Name	City	State
Australia	Royal North Shore Hospital	St Leonards	New South Wales
Brazil	Hospital Israelita Albert Einstein	Sao Paulo
Chile	Universidad de Concepcion	Concepcion	Bio Bio
China	Tongji Hospital of Tongji University	Shanghai
Colombia	Clinica Universidad de La Sabana	Chia	Cundinamarca
Finland	HUS Children and Adolescents Park Hospital Clinical Trial Unit	Helsinki	Stenbäckinkatu 11
France	Hôpital Lapeyronie	Montpellier
France	Hopital Lariboisiere	Paris
Hong Kong	Queen Mary Hospital	Hong Kong
Italy	IRCCS Istituto Giannina Gaslini	Genoa
Japan	Kyushu University Hospital	Fukuoka
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Oita University Hospital	Yufu	Oita
Korea, Republic of	Seoul National University Hospital	Seoul
Malaysia	Hospital Kuala Lampur	Kuala Lumpur
Netherlands	Amsterdam University Medical Center	Amsterdam	North Holland
Poland	Szpital Centrum Medyczne Medyk	Rzeszow	Podkarpackie
South Africa	University of Cape Town	Rondebosch	Cape Town
Spain	Hospital Universitario Ramon y Cajal	Madrid
United Kingdom	Royal National Orthropaedic Hospital NHS Trust	Middlesex	Greater London
United States	University of California Los Angeles (UCLA) Medical Center	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Countries where clinical trial is conducted

United States,  Australia,  Brazil,  Chile,  China,  Colombia,  Finland,  France,  Hong Kong,  Italy,  Japan,  Korea, Republic of,  Malaysia,  Netherlands,  Poland,  South Africa,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of new HO lesions adjudicated as positive based on computed tomography (CT)		At Week 56
Primary	Incidence and severity of treatment-emergent adverse events of special interest (AESIs)		Baseline to Week 56
Secondary	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 Week 28, Week 56 and Week 84
Secondary	Occurrence of clinician-assessed flare-ups	Reported as Yes/No; Week 84 Only for Patients on Extended Treatment	Through Week 28, Week 56 and Week 84
Secondary	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 Week 28 and Week 56
Secondary	Occurrence of patient-reported flare-ups	Reported as Yes/No	Through Weeks 28 and Week 56
Secondary	Occurrence of new HO lesions adjudicated as positive based on CT	Reported as Yes/No; Week 84 Only for Patients on Extended Treatment	At Week 28, Week 56 and Week 84
Secondary	Total volume of new HO lesions adjudicated as positive based on CT	Week 84 Only for Patients on Extended Treatment	At Week 28, Week 56 and Week 84
Secondary	Number of new HO lesions adjudicated as positive based on CT	Week 84 Only for Patients on Extended Treatment	At Week 28 and Week 84
Secondary	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 Week 28 and Week 56
Secondary	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 to Week 28 and Week 56
Secondary	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 Week 28 and Week 56
Secondary	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	Baseline to Week 28 and Week 56
Secondary	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	Baseline to Week 28 and Week 56
Secondary	Concentration of total activin A in serum over time		Through Week 56
Secondary	Concentration of garetosmab in serum over time		Through Week 56
Secondary	Incidence of anti-drug antibodies (ADA) to garetosmab over time		Through Week 56
Secondary	Titer of ADA to garetosmab over time		Through Week 56

External Links

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