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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05394116




Registration number
NCT05394116
Ethics application status
Date submitted
4/05/2022
Date registered
27/05/2022

Titles & IDs
Public title
A Study to Assess Safety, Tolerability and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP)
Scientific title
Phase 3 Randomized, Placebo-Controlled Study to Assess Safety, Tolerability, and Efficacy of Garetosmab in Patients With Fibrodysplasia Ossificans Progressiva
Secondary ID [1] 0 0
2022-000880-40
Secondary ID [2] 0 0
R2477-FOP-2175
Universal Trial Number (UTN)
Trial acronym
OPTIMA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Fibrodysplasia Ossificans Progressiva 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Injuries and Accidents 0 0 0 0
Other injuries and accidents

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Garetosmab
Treatment: Drugs - Placebo

Experimental: High dose Garetosmab - Garetosmab is administered by intravenous (IV) administration every 4 weeks (Q4W)

Experimental: Low dose Garetosmab - Garetosmab is administered by IV administration Q4W

Experimental: Placebo - Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV Q4W.


Treatment: Drugs: Garetosmab
Garetosmab is supplied as a liquid drug product and will be administered IV.

Treatment: Drugs: Placebo
Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of new HO lesions
Timepoint [1] 0 0
At Week 56
Primary outcome [2] 0 0
Incidence and severity of treatment-emergent adverse events of special interest (AESIs)
Timepoint [2] 0 0
Baseline to Week 56
Secondary outcome [1] 0 0
Number of clinician-assessed flare-ups
Timepoint [1] 0 0
Through Weeks 28, 56 and 84
Secondary outcome [2] 0 0
Occurrence of new HO lesions
Timepoint [2] 0 0
At Weeks 28, 56 and 84
Secondary outcome [3] 0 0
Total volume of new HO lesions
Timepoint [3] 0 0
At Weeks 28, 56 and 84
Secondary outcome [4] 0 0
Occurrence of patient-reported flare-ups
Timepoint [4] 0 0
Through Weeks 28 and 56
Secondary outcome [5] 0 0
Number of new HO lesions
Timepoint [5] 0 0
At week 28 and 84
Secondary outcome [6] 0 0
Occurrence of clinician-assessed flare-ups
Timepoint [6] 0 0
Through Weeks 28, 56 and 84
Secondary outcome [7] 0 0
Number of patient-reported flare-ups
Timepoint [7] 0 0
Through Weeks 28 and 56
Secondary outcome [8] 0 0
Change in joint function assessment by physician using cumulative analog joint involvement scale (CAJIS)
Timepoint [8] 0 0
Baseline to Weeks 28 and 56
Secondary outcome [9] 0 0
Change in pulmonary function as assessed by spirometry
Timepoint [9] 0 0
Baseline at Weeks 28 and 56
Secondary outcome [10] 0 0
Change in disease severity as assessed by the Patient Global Impression of Severity (PGIS)
Timepoint [10] 0 0
Baseline to Weeks 28 and 56
Secondary outcome [11] 0 0
Change in disease severity as assessed by the Patient's Global Impression of Change (PGIC)
Timepoint [11] 0 0
At Weeks 28 and 56
Secondary outcome [12] 0 0
Change in disease severity as assessed by the Clinician's Global Impression of Change (CGIC)
Timepoint [12] 0 0
At Weeks 28 and 56
Secondary outcome [13] 0 0
Concentration of total activin A in serum over time
Timepoint [13] 0 0
Through Week 56
Secondary outcome [14] 0 0
Concentration of garetosmab in serum over time
Timepoint [14] 0 0
Through Week 56
Secondary outcome [15] 0 0
Incidence of anti-drug antibodies (ADA) to garetosmab over time
Timepoint [15] 0 0
Through Week 56
Secondary outcome [16] 0 0
Titer of ADA to garetosmab over time
Timepoint [16] 0 0
Through Week 56

Eligibility
Key inclusion criteria
Key

1. Clinical diagnosis of Fibrodysplasia Ossificans Progressiva (FOP) [(based on findings of congenital malformation of the great toes, episodic soft tissue swelling, and/or progressive Heterotopic Ossification (HO)]
2. Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation
3. FOP disease activity within 1 year of screening visit. FOP disease activity is defined as pain, swelling, stiffness, or other signs and symptoms associated with FOP flare-ups; or worsening of joint function, or radiographic progression of HO lesions (increase in size or number of HO lesions) with/without being associated with flare-up episodes
4. Willing and able to undergo CT imaging procedures and other procedures as defined in the protocol

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Cumulative Analog Joint Involvement Scale (CAJIS) score at screening >19
2. Participant 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
3. Previous history or diagnosis of cancer
4. Severely impaired renal function defined as estimated glomerular filtration rate <30 milliliter per minute (mL/min) (/1.73 m^2 calculated by the Modification of Diet in Renal Disease equation
5. Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) >9% at screening
6. History of poorly controlled hypertension, as defined by:

1. Systolic blood pressure =180 mm Hg or diastolic blood pressure =110 mm Hg at the screening visit
2. Systolic blood pressure of 160 mm Hg to 179 mm Hg or diastolic blood pressure of 100 mm Hg to 109 mm Hg at the screening visit, AND a history of end-organ damage (including history of left-ventricular hypertrophy, heart failure, angina, myocardial infarction, stroke, transient ischemic attack, peripheral arterial disease, end-stage renal disease, and moderate-to-advanced retinopathy
7. Known history of cerebral vascular malformation
8. Cardiovascular conditions such as New York Heart Association class III or IV heart failure, cardiomyopathy, intermittent claudication, myocardial infarction, or acute coronary syndrome within 6 months prior to screening; symptomatic ventricular cardiac arrhythmia
9. History of severe respiratory compromise requiring oxygen, respiratory support (eg, bilevel positive airway pressure [biPAP] or continuous positive airway pressure [CPAP]), or a history of aspiration pneumonia requiring hospitalization
10. Prior use in the past year and concomitant use of bisphosphonates
11. Concurrent participation in another interventional clinical study or a non-interventional study with radiographic measures or invasive procedures (eg, collection of blood or tissue samples)
12. Treatment with another investigational drug, denosumab, imatinib or isotretinoin in the last 30 days or within 5 half-lives of the investigational drug, whichever is longer
13. Pregnant or breastfeeding women
14. Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception, as defined in the protocol
15. Male patients with WOCBP partners who are not willing to use condoms with WOCBP partners to prevent potential fetal exposure, as defined in the protocol

Note: Other protocol defined Inclusion/Exclusion Criteria apply

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/11/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
25/09/2026
Actual
Sample size
Target
Accrual to date
Final
63
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Royal North Shore Hospital - St Leonards
Recruitment postcode(s) [1] 0 0
2065 - St Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Tennessee
Country [3] 0 0
Brazil
State/province [3] 0 0
Sao Paulo
Country [4] 0 0
Chile
State/province [4] 0 0
Bio Bio
Country [5] 0 0
China
State/province [5] 0 0
Shanghai
Country [6] 0 0
Colombia
State/province [6] 0 0
Cundinamarca
Country [7] 0 0
Finland
State/province [7] 0 0
Stenbäckinkatu 11
Country [8] 0 0
France
State/province [8] 0 0
Montpellier
Country [9] 0 0
France
State/province [9] 0 0
Paris
Country [10] 0 0
Hong Kong
State/province [10] 0 0
Hong Kong
Country [11] 0 0
Italy
State/province [11] 0 0
Genoa
Country [12] 0 0
Japan
State/province [12] 0 0
Aichi
Country [13] 0 0
Japan
State/province [13] 0 0
Oita
Country [14] 0 0
Japan
State/province [14] 0 0
Fukuoka
Country [15] 0 0
Korea, Republic of
State/province [15] 0 0
Seoul
Country [16] 0 0
Malaysia
State/province [16] 0 0
Kuala Lumpur
Country [17] 0 0
Netherlands
State/province [17] 0 0
North Holland
Country [18] 0 0
Poland
State/province [18] 0 0
Podkarpackie
Country [19] 0 0
South Africa
State/province [19] 0 0
Cape Town
Country [20] 0 0
Spain
State/province [20] 0 0
Madrid
Country [21] 0 0
United Kingdom
State/province [21] 0 0
Greater London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Regeneron Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trial Management
Address 0 0
Regeneron Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Clinical Trials Administrator
Address 0 0
Country 0 0
Phone 0 0
844-734-6643
Fax 0 0
Email 0 0
clinicaltrials@regeneron.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR), Analytic code
When will data be available (start and end dates)?
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 or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
* made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
* the legal authority to share the data, and
* ensured the ability to protect participant privacy
Available to whom?
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
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://vivli.org/


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT05394116