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

• ClinicalTrials.gov Identifier: NCT04577820
• Recruitment Status: Withdrawn
• First Posted: October 8, 2020
• Last Update Posted: November 1, 2021
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Fibrodyplasia Ossificans Progressiva (FOP); Heterotopic Ossification (HO)	Drug: garetosmab	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Efficacy and Safety of Garetosmab in Japanese Adult Patients With Fibrodysplasia Ossificans Progressiva
• Estimated Study Start Date: October 13, 2021
• Estimated Primary Completion Date: March 1, 2022
• Estimated Study Completion Date: October 8, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: garetosmab	Drug: garetosmab; Repeated doses administered intravenously (IV) every four weeks (Q4W); Other Name: REGN2477

Outcome Measures

Primary Outcome Measures :

1. Incidence and severity of treatment-emergent adverse event (TEAEs) [ Time Frame: Through week 28 ]
2. Number of new HO lesions as assessed by CT [ Time Frame: At week 28 ]

Secondary Outcome Measures :

1. Total volume of new HO lesions as assessed by CT [ Time Frame: At week 28 ]
2. Number of new HO lesions as assessed by positron emission tomography (PET) [ Time Frame: At week 28 ]
3. Total lesion activity in new HO lesions as assessed by PET [ Time Frame: At week 28 ]
4. Percent of patients with new HO lesions as assessed by CT [ Time Frame: At week 28 ]
5. Percent of patients with new HO lesions as assessed by PET [ Time Frame: At week 28 ]
6. Percent of patients with investigator-assessed flare-ups [ Time Frame: Baseline to week 28 ]
7. Percent of patients with investigator-assessed flare-ups [ Time Frame: Baseline to week 56 ]
8. Percent of patients with flare-ups assessed by patient e-diary [ Time Frame: Baseline to week 28 ]
9. Percent of patients with flare-ups assessed by patient e-diary [ Time Frame: Baseline to week 56 ]
10. Number of new HO lesions as assessed by CT [ Time Frame: At week 56 ]
11. Total volume of new HO lesions as assessed by CT [ Time Frame: At week 56 ]
12. Percent of patients with new HO lesions as assessed by CT [ Time Frame: At week 56 ]
13. Number of new HO lesions as assessed by PET [ Time Frame: At week 56 ]
14. Total lesion activity in new HO lesions as assessed by PET [ Time Frame: At week 56 ]
15. Percent of patients with new HO lesions as assessed by PET [ Time Frame: At week 56 ]
16. Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET [ Time Frame: Baseline and week 28 ]
17. Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET [ Time Frame: Baseline and week 56 ]
18. Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET [ Time Frame: Baseline and week 28 ]
19. Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET [ Time Frame: Baseline and week 56 ]
20. Change in total lesion activity by PET [ Time Frame: Baseline and week 28 ]
21. Change in total lesion activity by PET [ Time Frame: Baseline and week 56 ]
22. Percent change in total lesion activity by PET [ Time Frame: Baseline and week 28 ]
23. Percent change in total lesion activity by PET [ Time Frame: Baseline and week 56 ]
24. Change in the total volume of HO lesions as assessed by CT [ Time Frame: Baseline and week 28 ]
25. Change in the total volume of HO lesions as assessed by CT [ Time Frame: Baseline and week 56 ]
26. Percent change in the total volume of HO lesions as assessed by CT [ Time Frame: Baseline and week 28 ]
27. Percent change in the total volume of HO lesions as assessed by CT [ Time Frame: Baseline and week 56 ]
28. Change in number of HO lesions as assessed by PET [ Time Frame: Baseline and week 28 ]
    HO lesions defined as target and new lesions relative to baseline.
29. Change in number of HO lesions as assessed by PET [ Time Frame: Baseline and week 56 ]
    Defined above
30. Change in the number of HO lesions detectable by CT [ Time Frame: Baseline and week 28 ]
    Defined above
31. Change in the number of HO lesions detectable by CT [ Time Frame: Baseline and week 56 ]
    Defined above
32. Time-weighted average (standardized area under curve [AUC]) change in daily pain due to FOP, as measured using the daily numeric rating scale (NRS) [ Time Frame: Baseline through week 28 ]
    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).
33. Time-weighted average (standardized AUC) change in daily pain due to FOP, as measured using the daily NRS [ Time Frame: Baseline through week 56 ]
34. Total dosage of glucocorticoids use [ Time Frame: Through week 56 ]
35. Incidence and severity of TEAEs [ Time Frame: Through week 56 ]
36. Concentration of total activin A in serum over time [ Time Frame: Through week 56 ]
37. Pharmacokinetic (Pk) Profile - concentrations of garetosmab in serum over time [ Time Frame: Through week 56 ]
38. Immunogenicity as measured by Anti-drug antibodies (ADA) to garetosmab over time [ Time Frame: Through week 28 ]
39. Percent change from baseline in biomarkers of bone formation levels in serum [ Time Frame: Through week 28 ]

Eligibility Criteria

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

Criteria

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.

Contacts and Locations

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT04577820
• Other Study ID Numbers: R2477-FOP-1940
• First Posted: October 8, 2020
• Last Update Posted: November 1, 2021
• Last Verified: October 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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.
• 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
• URL: https://vivli.org/

• 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

Additional relevant MeSH terms:

Myositis Ossificans; Ossification, Heterotopic; Pathologic Processes; Myositis; Muscular Diseases; Musculoskeletal Diseases