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

Fibrodyplasia Ossificans Progressiva (FOP) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04577820
• Other study ID #: R2477-FOP-1940
• Status: Withdrawn
• Phase: Phase 3
• Start date: October 13, 2021
• Est. completion date: October 8, 2022

Study information

• Verified date: October 2021
• Source: Regeneron Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: October 8, 2022
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• garetosmab
Repeated doses administered intravenously (IV) every four weeks (Q4W)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Regeneron Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and severity of treatment-emergent adverse event (TEAEs)		Through week 28
Primary	Number of new HO lesions as assessed by CT		At week 28
Secondary	Total volume of new HO lesions as assessed by CT		At week 28
Secondary	Number of new HO lesions as assessed by positron emission tomography (PET)		At week 28
Secondary	Total lesion activity in new HO lesions as assessed by PET		At week 28
Secondary	Percent of patients with new HO lesions as assessed by CT		At week 28
Secondary	Percent of patients with new HO lesions as assessed by PET		At week 28
Secondary	Percent of patients with investigator-assessed flare-ups		Baseline to week 28
Secondary	Percent of patients with investigator-assessed flare-ups		Baseline to week 56
Secondary	Percent of patients with flare-ups assessed by patient e-diary		Baseline to week 28
Secondary	Percent of patients with flare-ups assessed by patient e-diary		Baseline to week 56
Secondary	Number of new HO lesions as assessed by CT		At week 56
Secondary	Total volume of new HO lesions as assessed by CT		At week 56
Secondary	Percent of patients with new HO lesions as assessed by CT		At week 56
Secondary	Number of new HO lesions as assessed by PET		At week 56
Secondary	Total lesion activity in new HO lesions as assessed by PET		At week 56
Secondary	Percent of patients with new HO lesions as assessed by PET		At week 56
Secondary	Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET		Baseline and week 28
Secondary	Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET		Baseline and week 56
Secondary	Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET		Baseline and week 28
Secondary	Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET		Baseline and week 56
Secondary	Change in total lesion activity by PET		Baseline and week 28
Secondary	Change in total lesion activity by PET		Baseline and week 56
Secondary	Percent change in total lesion activity by PET		Baseline and week 28
Secondary	Percent change in total lesion activity by PET		Baseline and week 56
Secondary	Change in the total volume of HO lesions as assessed by CT		Baseline and week 28
Secondary	Change in the total volume of HO lesions as assessed by CT		Baseline and week 56
Secondary	Percent change in the total volume of HO lesions as assessed by CT		Baseline and week 28
Secondary	Percent change in the total volume of HO lesions as assessed by CT		Baseline and week 56
Secondary	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
Secondary	Change in number of HO lesions as assessed by PET	Defined above	Baseline and week 56
Secondary	Change in the number of HO lesions detectable by CT	Defined above	Baseline and week 28
Secondary	Change in the number of HO lesions detectable by CT	Defined above	Baseline and week 56
Secondary	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
Secondary	Time-weighted average (standardized AUC) change in daily pain due to FOP, as measured using the daily NRS		Baseline through week 56
Secondary	Total dosage of glucocorticoids use		Through week 56
Secondary	Incidence and severity of TEAEs		Through week 56
Secondary	Concentration of total activin A in serum over time		Through week 56
Secondary	Pharmacokinetic (Pk) Profile - concentrations of garetosmab in serum over time		Through week 56
Secondary	Immunogenicity as measured by Anti-drug antibodies (ADA) to garetosmab over time		Through week 28
Secondary	Percent change from baseline in biomarkers of bone formation levels in serum		Through week 28