Back to resultsStudy to Assess the Efficacy and Safety of Garetosmab in Japanese Adult Patients With Fibrodysplasia Ossificans Progressiva (FOP)
Primary Purpose
Fibrodyplasia Ossificans Progressiva (FOP), Heterotopic Ossification (HO)
Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
garetosmab
Sponsored by
About this trial
This is an interventional treatment trial for Fibrodyplasia Ossificans Progressiva (FOP)
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
garetosmab
Arm Description
Outcomes
Primary Outcome Measures
Incidence and severity of treatment-emergent adverse event (TEAEs)
Number of new HO lesions as assessed by CT
Secondary Outcome Measures
Total volume of new HO lesions as assessed by CT
Number of new HO lesions as assessed by positron emission tomography (PET)
Total lesion activity in new HO lesions as assessed by PET
Percent of patients with new HO lesions as assessed by CT
Percent of patients with new HO lesions as assessed by PET
Percent of patients with investigator-assessed flare-ups
Percent of patients with investigator-assessed flare-ups
Percent of patients with flare-ups assessed by patient e-diary
Percent of patients with flare-ups assessed by patient e-diary
Number of new HO lesions as assessed by CT
Total volume of new HO lesions as assessed by CT
Percent of patients with new HO lesions as assessed by CT
Number of new HO lesions as assessed by PET
Total lesion activity in new HO lesions as assessed by PET
Percent of patients with new HO lesions as assessed by PET
Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
Change in total lesion activity by PET
Change in total lesion activity by PET
Percent change in total lesion activity by PET
Percent change in total lesion activity by PET
Change in the total volume of HO lesions as assessed by CT
Change in the total volume of HO lesions as assessed by CT
Percent change in the total volume of HO lesions as assessed by CT
Percent change in the total volume of HO lesions as assessed by CT
Change in number of HO lesions as assessed by PET
HO lesions defined as target and new lesions relative to baseline.
Change in number of HO lesions as assessed by PET
Defined above
Change in the number of HO lesions detectable by CT
Defined above
Change in the number of HO lesions detectable by CT
Defined above
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).
Time-weighted average (standardized AUC) change in daily pain due to FOP, as measured using the daily NRS
Total dosage of glucocorticoids use
Incidence and severity of TEAEs
Concentration of total activin A in serum over time
Pharmacokinetic (Pk) Profile - concentrations of garetosmab in serum over time
Immunogenicity as measured by Anti-drug antibodies (ADA) to garetosmab over time
Percent change from baseline in biomarkers of bone formation levels in serum
Full Information
NCT ID
NCT04577820
First Posted
September 30, 2020
Last Updated
October 25, 2021
Sponsor
Regeneron Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT04577820
Brief Title
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
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Withdrawn
Why Stopped
Phase 2 Study R2477-FOP-1940 has been withdrawn and the next phase of the development program is being planned
Study Start Date
October 13, 2021 (Anticipated)
Primary Completion Date
March 1, 2022 (Anticipated)
Study Completion Date
October 8, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Regeneron Pharmaceuticals
4. Oversight
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
5. 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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibrodyplasia Ossificans Progressiva (FOP), Heterotopic Ossification (HO)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
garetosmab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
garetosmab
Other Intervention Name(s)
REGN2477
Intervention Description
Repeated doses administered intravenously (IV) every four weeks (Q4W)
Primary Outcome Measure Information:
Title
Incidence and severity of treatment-emergent adverse event (TEAEs)
Time Frame
Through week 28
Title
Number of new HO lesions as assessed by CT
Time Frame
At week 28
Secondary Outcome Measure Information:
Title
Total volume of new HO lesions as assessed by CT
Time Frame
At week 28
Title
Number of new HO lesions as assessed by positron emission tomography (PET)
Time Frame
At week 28
Title
Total lesion activity in new HO lesions as assessed by PET
Time Frame
At week 28
Title
Percent of patients with new HO lesions as assessed by CT
Time Frame
At week 28
Title
Percent of patients with new HO lesions as assessed by PET
Time Frame
At week 28
Title
Percent of patients with investigator-assessed flare-ups
Time Frame
Baseline to week 28
Title
Percent of patients with investigator-assessed flare-ups
Time Frame
Baseline to week 56
Title
Percent of patients with flare-ups assessed by patient e-diary
Time Frame
Baseline to week 28
Title
Percent of patients with flare-ups assessed by patient e-diary
Time Frame
Baseline to week 56
Title
Number of new HO lesions as assessed by CT
Time Frame
At week 56
Title
Total volume of new HO lesions as assessed by CT
Time Frame
At week 56
Title
Percent of patients with new HO lesions as assessed by CT
Time Frame
At week 56
Title
Number of new HO lesions as assessed by PET
Time Frame
At week 56
Title
Total lesion activity in new HO lesions as assessed by PET
Time Frame
At week 56
Title
Percent of patients with new HO lesions as assessed by PET
Time Frame
At week 56
Title
Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
Time Frame
Baseline and week 28
Title
Change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
Time Frame
Baseline and week 56
Title
Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
Time Frame
Baseline and week 28
Title
Percent change in mean maximum standard uptake volume (SUVmax) of individual active HO site(s) by PET
Time Frame
Baseline and week 56
Title
Change in total lesion activity by PET
Time Frame
Baseline and week 28
Title
Change in total lesion activity by PET
Time Frame
Baseline and week 56
Title
Percent change in total lesion activity by PET
Time Frame
Baseline and week 28
Title
Percent change in total lesion activity by PET
Time Frame
Baseline and week 56
Title
Change in the total volume of HO lesions as assessed by CT
Time Frame
Baseline and week 28
Title
Change in the total volume of HO lesions as assessed by CT
Time Frame
Baseline and week 56
Title
Percent change in the total volume of HO lesions as assessed by CT
Time Frame
Baseline and week 28
Title
Percent change in the total volume of HO lesions as assessed by CT
Time Frame
Baseline and week 56
Title
Change in number of HO lesions as assessed by PET
Description
HO lesions defined as target and new lesions relative to baseline.
Time Frame
Baseline and week 28
Title
Change in number of HO lesions as assessed by PET
Description
Defined above
Time Frame
Baseline and week 56
Title
Change in the number of HO lesions detectable by CT
Description
Defined above
Time Frame
Baseline and week 28
Title
Change in the number of HO lesions detectable by CT
Description
Defined above
Time Frame
Baseline and week 56
Title
Time-weighted average (standardized area under curve [AUC]) change in daily pain due to FOP, as measured using the daily numeric rating scale (NRS)
Description
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).
Time Frame
Baseline through week 28
Title
Time-weighted average (standardized AUC) change in daily pain due to FOP, as measured using the daily NRS
Time Frame
Baseline through week 56
Title
Total dosage of glucocorticoids use
Time Frame
Through week 56
Title
Incidence and severity of TEAEs
Time Frame
Through week 56
Title
Concentration of total activin A in serum over time
Time Frame
Through week 56
Title
Pharmacokinetic (Pk) Profile - concentrations of garetosmab in serum over time
Time Frame
Through week 56
Title
Immunogenicity as measured by Anti-drug antibodies (ADA) to garetosmab over time
Time Frame
Through week 28
Title
Percent change from baseline in biomarkers of bone formation levels in serum
Time Frame
Through week 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trial Management
Organizational Affiliation
Regeneron Pharmaceuticals
Official's Role
Study Director
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 URL
https://vivli.org/
Learn more about this trial
Study to Assess the Efficacy and Safety of Garetosmab in Japanese Adult Patients With Fibrodysplasia Ossificans Progressiva (FOP)
We'll reach out to this number within 24 hrs