Study to Assess the Efficacy and Safety of Garetosmab in Japanese Adult Patients With Fibrodysplasia Ossificans Progressiva (FOP)

Study Overview
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Brief Summary
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The primary safety objective of the study is to assess the safety and tolerability of garetosmab in Japanese male and female adult patients with FOP. The primary efficacy objective of the study is to assess the effect of garetosmab on Heterotopic ossification (HO) in Japanese adult patients with FOP, as determined by the number of new heterotopic bone lesions identified by computed tomography (CT).

Official Title
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Evaluation of Efficacy and Safety of Garetosmab in Japanese Adult Patients With Fibrodysplasia Ossificans Progressiva

Conditions
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Fibrodyplasia Ossificans Progressiva (FOP), Heterotopic Ossification (HO)

Intervention / Treatment
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* Drug: garetosmab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Clinical diagnosis of FOP (based on findings of congenital malformation of the great toes, episodic soft tissue swelling, and/or progressive HO) Confirmation of FOP diagnosis with documentation of any Type I activin A receptor (ACVR1) mutation FOP disease activity, as defined in the protocol, within 1 year of screening visit Willing and able to undergo PET and CT imaging procedures and other procedures as defined in this study Able to understand and complete study-related questionnaires and diaries (assistance from caregivers is allowed) Key Exclusion Criteria: Patient 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 mL/min/1.73 m2 calculated by the Modification of Diet in Renal Disease equation (1 retest is allowed) Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) >9% at screening (1 retest allowed) History of severe respiratory compromise, as defined in protocol Concurrent participation in another interventional clinical study or a non-interventional study with radiographic measures or invasive procedures Pregnant or breastfeeding women NOTE: Other protocol defined inclusion/exclusion criteria apply.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: garetosmab<br> | Drug: garetosmab<br>* Repeated doses administered intravenously (IV) every four weeks (Q4W)<br>* Other names: REGN2477;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of treatment-emergent adverse event (TEAEs) |  | Through week 28 | 
| Number of new HO lesions as assessed by CT |  | At week 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total volume of new HO lesions as assessed by CT |  | At week 28 | 
| Number of new HO lesions as assessed by positron emission tomography (PET) |  | At week 28 | 
| Total lesion activity in new HO lesions as assessed by PET |  | At week 28 | 
| Percent of patients with new HO lesions as assessed by CT |  | At week 28 | 
| Percent of patients with new HO lesions as assessed by PET |  | At week 28 | 
| Percent of patients with investigator-assessed flare-ups |  | Baseline to week 28 | 
| Percent of patients with investigator-assessed flare-ups |  | Baseline to week 56 | 
| Percent of patients with flare-ups assessed by patient e-diary |  | Baseline to week 28 | 
| Percent of patients with flare-ups assessed by patient e-diary |  | Baseline to week 56 | 
| Number of new HO lesions as assessed by CT |  | At week 56 | 
| Total volume of new HO lesions as assessed by CT |  | At week 56 | 
| Percent of patients with new HO lesions as assessed by CT |  | At week 56 | 
| Number of new HO lesions as assessed by PET |  | At week 56 | 
| Total lesion activity in new HO lesions as assessed by PET |  | At week 56 | 
| Percent of patients with new HO lesions as assessed by PET |  | At week 56 | 
| Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET |  | Baseline and week 28 | 
| Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET |  | Baseline and week 56 | 
| Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET |  | Baseline and week 28 | 
| Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET |  | Baseline and week 56 | 
| Change in total lesion activity by PET |  | Baseline and week 28 | 
| Change in total lesion activity by PET |  | Baseline and week 56 | 
| Percent change in total lesion activity by PET |  | Baseline and week 28 | 
| Percent change in total lesion activity by PET |  | Baseline and week 56 | 
| Change in the total volume of HO lesions as assessed by CT |  | Baseline and week 28 | 
| Change in the total volume of HO lesions as assessed by CT |  | Baseline and week 56 | 
| Percent change in the total volume of HO lesions as assessed by CT |  | Baseline and week 28 | 
| Percent change in the total volume of HO lesions as assessed by CT |  | Baseline and week 56 | 
| Change in number of HO lesions as assessed by PET | HO lesions defined as target and new lesions relative to baseline. | Baseline and week 28 | 
| Change in number of HO lesions as assessed by PET | Defined above | Baseline and week 56 | 
| Change in the number of HO lesions detectable by CT | Defined above | Baseline and week 28 | 
| Change in the number of HO lesions detectable by CT | Defined above | Baseline and week 56 | 
| Time-weighted average (standardized area under curve [AUC]) change in daily pain due to FOP, as measured using the daily numeric rating scale (NRS) | The NRS is a categorical rating scale used by patients to rate their pain associated with FOP. Patients will be asked to rate their pain on a scale that ranges from 0 (no pain) to 10 (worst possible pain). | Baseline through week 28 | 
| Time-weighted average (standardized AUC) change in daily pain due to FOP, as measured using the daily NRS |  | Baseline through week 56 | 
| Total dosage of glucocorticoids use |  | Through week 56 | 
| Incidence and severity of TEAEs |  | Through week 56 | 
| Concentration of total activin A in serum over time |  | Through week 56 | 
| Pharmacokinetic (Pk) Profile - concentrations of garetosmab in serum over time |  | Through week 56 | 
| Immunogenicity as measured by Anti-drug antibodies (ADA) to garetosmab over time |  | Through week 28 | 
| Percent change from baseline in biomarkers of bone formation levels in serum |  | Through week 28 |