OPTIMA: The Examination of Safety and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP)
Study Details
Study Description
Brief Summary
The study population consists of patients with Fibrodysplasia ossificans progressiva (FOP).
Key primary objectives are:
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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)
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To assess the safety and tolerability of garetosmab versus placebo from baseline to week 56
Key Secondary Objectives:
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To assess the effect of high dose garetosmab versus placebo on the number per participant of clinician-assessed flare-up episodes to week 56
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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
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To assess the effect of low dose garetosmab versus placebo on the number per patient of clinician-assessed flare-up episodes to week 56
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| 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:
|
| 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:
|
| Experimental: Placebo Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV. |
Drug: Placebo
Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV.
|
Outcome Measures
Primary Outcome Measures
- Number of new HO lesions adjudicated as positive based on CT [Through week 56]
- Incidence and severity of treatment-emergent adverse events of special interest (AESIs) [Baseline to Week 56]
Secondary Outcome Measures
- Number of clinician-assessed flare-ups [Through Week 28 and Week 56]
Investigator assess flare-up events according to his/her medical judgment. A FOP flare-up is characterized as episodic, painful inflammatory soft tissue swelling
- Occurrence of clinician-assessed flare-ups [Through Weeks 28 and 56]
Reported as Yes/No
- Number of patient-reported flare-ups [Through Weeks 28 and 56]
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.
- Occurrence of patient-reported flare-ups [Through Weeks 28 and 56]
Reported as Yes/No
- Occurrence of new HO lesions adjudicated as positive based on CT [Weeks 28 and 56]
Reported as Yes/No
- Total volume of new HO lesions adjudicated as positive based on CT [Weeks 28 and 56]
- Number of new HO lesions adjudicated as positive based on CT [Week 28]
- Change in joint function assessment by physician using cumulative analog joint involvement scale (CAJIS) [Baseline to Week 28 and 56]
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
- Change in pulmonary function as assessed by spirometry [Baseline to Week 28 and 56]
Forced vital capacity (FVC) and Forced expiratory volume in 1 second (FEV1) and the ratio of FEV1/FVC will be determined by spirometry.
- Change in disease severity as assessed by the Patient Global Impression of Severity (PGIS) [Baseline to Week 28 and 56]
PGIS is a single item, self-administered questionnaire to assess the patient's global impression of severity
- Change in disease severity as assessed by the Patient's Global Impression of Change (PGIC) [Baseline to Week 28 and 56]
PGIC is a single item, self-administered questionnaire to assess the patient's global impression of change
- Change in disease severity as assessed by the Clinician's Global Impression of Change (CGIC) [Baseline to Week 28 and 56]
CGIC is a single-item questionnaire to assess the clinician's global impression of change
- Concentration of total activin A in serum over time [Baseline to Week 56]
- Concentrations of garetosmab in serum [Baseline to Week 56]
- Immunogenicity of as measured by the presence of anti-drug antibodies (ADA) to garetosmab [Baseline to Week 56]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Male or female 18 years or older at screening
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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)]
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Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation
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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
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Willing and able to undergo CT imaging procedures and other procedures as defined in the protocol
Key Exclusion Criteria:
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Cumulative Analog Joint Involvement Scale (CAJIS) score at screening >19
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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
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Previous history or diagnosis of cancer
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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
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Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) >9% at screening
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History of poorly controlled hypertension as defined, as defined by:
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Systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg at the screening visit
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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
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Known history of cerebral vascular malformation
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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
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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
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Prior use in the past year and concomitant use of bisphosphonates
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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).
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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
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Pregnant or breastfeeding women
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Women of childbearing potential (WOCBP)* who are unwilling to practice highly effective contraception
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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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R2477-FOP-2175
- 2022-000880-40