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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Fibrodyplasia Ossificans Progressiva (FOP); Heterotopic Ossification (HO)
• Intervention / Treatment: Drug: garetosmab

• Study Type: Interventional
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: garetosmab	Drug: garetosmab; Repeated doses administered intravenously (IV) every four weeks (Q4W); Other Names: REGN2477

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Anticipated): October 13, 2021
• Primary Completion (Anticipated): March 1, 2022
• Study Completion (Anticipated): October 8, 2022

Study Registration Dates

• First Submitted: September 30, 2020
• First Submitted That Met QC Criteria: September 30, 2020
• First Posted (Actual): October 8, 2020

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Musculoskeletal Diseases; Muscular Diseases; Myositis; Myositis Ossificans; Ossification, Heterotopic
• Other Study ID Numbers: R2477-FOP-1940

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes