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

Phase 3

Withdrawn

• Conditions: Fibrodyplasia Ossificans Progressiva (FOP); Heterotopic Ossification (HO)
• Interventions: Drug: garetosmab

• Registration Number: NCT04577820
• Lead Sponsor: Regeneron Pharmaceuticals

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).

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-09-30
• Study First Submitted QC: 2020-09-30
• Study First Posted: 2020-10-08
• Status Verified: 2021-10
• Study Start: 2021-10-13
• Last Update Submitted: 2021-10-25
• Last Update Posted: 2021-11-01
• Primary Completion: 2022-03-01
• Study Completion: 2022-10-08

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
garetosmab	garetosmab	-

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Total lesion activity in new HO lesions as assessed by PET	At week 56
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
Number of 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 56
Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET	Baseline and week 56
Percent change in total lesion activity by PET	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)	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).
Incidence and severity of TEAEs	Through week 56
Percent of patients with new HO lesions as assessed by PET	At week 56
Total volume of new HO lesions as assessed by CT	At week 56
Number of new HO lesions as assessed by positron emission tomography (PET)	At week 28
Percent of patients with new HO lesions as assessed by CT	At week 56
Percent of patients with investigator-assessed flare-ups	Baseline to week 56
Change in number of HO lesions as assessed by PET	Baseline and week 56	Defined above
Time-weighted average (standardized AUC) change in daily pain due to FOP, as measured using the daily NRS	Baseline 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
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 56
Change in the number of HO lesions detectable by CT	Baseline and week 56	Defined above
Total dosage of glucocorticoids use	Through week 56
Concentration of total activin A in serum over time	Through week 56
Change in total lesion activity by PET	Baseline and week 56