The Examination of Safety and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP)

• Status: Not yet recruiting
• Trial end date: 2026-03-08
• Target enrollment: 0
• Participant gender: All

Summary

The study population consists of patients with Fibrodysplasia ossificans progressiva (FOP).

Key primary objectives are:

1. To assess the effect of high dose garetosmab versus placebo on the formation of new heterotopic ossification (HO) lesions from baseline to week 56, as determined by low-dose computed tomography (CT)

2. To assess the safety and tolerability of garetosmab versus placebo from baseline to week 56

Key Secondary Objectives:

1. To assess the effect of high dose garetosmab versus placebo on the number per participant of clinician-assessed flare-up episodes to week 56

2. To assess the effect of low dose garetosmab versus placebo on the formation of new HO lesions from baseline to week 56 as determined by CT

3. To assess the effect of low dose garetosmab versus placebo on the number per patient of clinician-assessed flare-up episodes to week 56

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Regeneron Pharmaceuticals

Criteria

Key Inclusion Criteria:

1. Male or female 18 years or older at screening

2. 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)]

3. Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation

4. 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

5. 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, 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

15. Male patients with WOCBP partners* who are not willing to use condoms with WOCBP partners to prevent potential fetal exposure

Note: Other protocol defined Inclusion/Exclusion Criteria apply