Clinical trial NCT04577820: Study to Assess the Efficacy and Safety of Garetosmab in Japanese Adult Patients With Fibrodysplasia Ossificans Progressiva (FOP)
Official title: Evaluation of Efficacy and Safety of Garetosmab in Japanese Adult Patients With Fibrodysplasia Ossificans Progressiva
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE3
Conditions: Fibrodyplasia Ossificans Progressiva (FOP)
Heterotopic Ossification (HO)
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2020-10-08
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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).


Eligibility 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.

Primary outcomes:
measure: Incidence and severity of treatment-emergent adverse event (TEAEs)
timeFrame: Through week 28
measure: Number of new HO lesions as assessed by CT
timeFrame: At week 28
Secondary outcomes:
measure: Total volume of new HO lesions as assessed by CT
timeFrame: At week 28
measure: Number of new HO lesions as assessed by positron emission tomography (PET)
timeFrame: At week 28
measure: Total lesion activity in new HO lesions as assessed by PET
timeFrame: At week 28
measure: Percent of patients with new HO lesions as assessed by CT
timeFrame: At week 28
measure: Percent of patients with new HO lesions as assessed by PET
timeFrame: At week 28
measure: Percent of patients with investigator-assessed flare-ups
timeFrame: Baseline to week 28
measure: Percent of patients with investigator-assessed flare-ups
timeFrame: Baseline to week 56
measure: Percent of patients with flare-ups assessed by patient e-diary
timeFrame: Baseline to week 28
measure: Percent of patients with flare-ups assessed by patient e-diary
timeFrame: Baseline to week 56
measure: Number of new HO lesions as assessed by CT
timeFrame: At week 56
measure: Total volume of new HO lesions as assessed by CT
timeFrame: At week 56
measure: Percent of patients with new HO lesions as assessed by CT
timeFrame: At week 56
measure: Number of new HO lesions as assessed by PET
timeFrame: At week 56
measure: Total lesion activity in new HO lesions as assessed by PET
timeFrame: At week 56
measure: Percent of patients with new HO lesions as assessed by PET
timeFrame: At week 56
measure: Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
timeFrame: Baseline and week 28
measure: Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
timeFrame: Baseline and week 56
measure: Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
timeFrame: Baseline and week 28
measure: Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
timeFrame: Baseline and week 56
measure: Change in total lesion activity by PET
timeFrame: Baseline and week 28
measure: Change in total lesion activity by PET
timeFrame: Baseline and week 56
measure: Percent change in total lesion activity by PET
timeFrame: Baseline and week 28
measure: Percent change in total lesion activity by PET
timeFrame: Baseline and week 56
measure: Change in the total volume of HO lesions as assessed by CT
timeFrame: Baseline and week 28
measure: Change in the total volume of HO lesions as assessed by CT
timeFrame: Baseline and week 56
measure: Percent change in the total volume of HO lesions as assessed by CT
timeFrame: Baseline and week 28
measure: Percent change in the total volume of HO lesions as assessed by CT
timeFrame: Baseline and week 56
measure: Change in number of HO lesions as assessed by PET
timeFrame: Baseline and week 28
measure: Change in number of HO lesions as assessed by PET
timeFrame: Baseline and week 56
measure: Change in the number of HO lesions detectable by CT
timeFrame: Baseline and week 28
measure: Change in the number of HO lesions detectable by CT
timeFrame: Baseline and week 56
measure: Time-weighted average (standardized area under curve [AUC]) change in daily pain due to FOP, as measured using the daily numeric rating scale (NRS)
timeFrame: Baseline through week 28
measure: Time-weighted average (standardized AUC) change in daily pain due to FOP, as measured using the daily NRS
timeFrame: Baseline through week 56
measure: Total dosage of glucocorticoids use
timeFrame: Through week 56
measure: Incidence and severity of TEAEs
timeFrame: Through week 56
measure: Concentration of total activin A in serum over time
timeFrame: Through week 56
measure: Pharmacokinetic (Pk) Profile - concentrations of garetosmab in serum over time
timeFrame: Through week 56
measure: Immunogenicity as measured by Anti-drug antibodies (ADA) to garetosmab over time
timeFrame: Through week 28
measure: Percent change from baseline in biomarkers of bone formation levels in serum
timeFrame: Through week 28
Other outcomes:
Locations:
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: