A Study to Assess Safety, Tolerability and Efficacy of Garetosmab Versus Placebo Administered Intravenously (IV) in Adult Participants With Fibrodysplasia Ossificans Progressiva (FOP)
- Conditions
- Fibrodysplasia Ossificans Progressiva
- Interventions
- Drug: Placebo
- Registration Number
- NCT05394116
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
This study is researching an experimental drug called garetosmab. The study is focused on adult patients with fibrodysplasia ossificans progressiva (FOP).
The aim of the study is to see how safe and effective the study drug is in patients with FOP.
The study is looking at several other research questions, including:
* What side effects may happen from receiving the study drug
* How much study drug is in the blood at different times
* Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 63
- 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)]
- Confirmation of FOP diagnosis with documentation of Type I activin A receptor (ACVR1) FOP causing mutation
- 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
- Willing and able to undergo CT imaging procedures and other procedures as defined in the protocol
Key
-
Cumulative Analog Joint Involvement Scale (CAJIS) score at screening >19
-
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
-
Previous history or diagnosis of cancer
-
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
-
Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) >9% at screening
-
History of poorly controlled hypertension, as defined by:
- Systolic blood pressure ≥180 mm Hg or diastolic blood pressure ≥110 mm Hg at the screening visit
- Systolic blood pressure of 160 mm Hg to 179 mm Hg or diastolic blood pressure of 100 mm Hg to 10^9 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
-
Known history of cerebral vascular malformation
-
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
-
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
-
Prior use in the past year and concomitant use of bisphosphonates
-
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)
-
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
-
Pregnant or breastfeeding women
-
Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception, as defined in the protocol
-
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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High dose Garetosmab Garetosmab Garetosmab is administered by intravenous (IV) administration every 4 weeks (Q4W) Low dose Garetosmab Garetosmab Garetosmab is administered by IV administration Q4W Placebo Placebo Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV Q4W.
- Primary Outcome Measures
Name Time Method Number of new HO lesions At Week 56 Incidence and severity of treatment-emergent adverse events of special interest (AESIs) Baseline to Week 56
- Secondary Outcome Measures
Name Time Method Concentration of garetosmab in serum over time Through Week 56 Incidence of anti-drug antibodies (ADA) to garetosmab over time Through Week 56 Titer of ADA to garetosmab over time Through Week 56 Number of clinician-assessed flare-ups Through Weeks 28, 56 and 84 Investigator assess flare-up events according to his/her medical judgment. A FOP flare-up is characterized as episodic, painful inflammatory soft tissue swelling.
Week 84 Only for Patients on Extended TreatmentOccurrence of new HO lesions At Weeks 28, 56 and 84 Reported as Yes/No
Week 84 Only for Patients on Extended TreatmentTotal volume of new HO lesions At Weeks 28, 56 and 84 Week 84 Only for Patients on Extended Treatment
Occurrence of patient-reported flare-ups Through Weeks 28 and 56 Reported as Yes/No
Number of new HO lesions At week 28 and 84 Week 84 Only for Patients on Extended Treatment
Occurrence of clinician-assessed flare-ups Through Weeks 28, 56 and 84 Reported as Yes/No
Week 84 Only for Patients on Extended TreatmentNumber of patient-reported flare-ups Through Weeks 28 and 56 Flare-up is defined as two or more of the following: pain, swelling, joint stiffness, or decrease in movement. The FOP flare-up dairy is a questionnaire and is self-completed by the participant daily.
Change in joint function assessment by physician using cumulative analog joint involvement scale (CAJIS) Baseline to Weeks 28 and 56 CAJIS is a clinician assessment of 15 major joints; each major joint rated normal unaffected (0), affected (1), or completely functionally ankylosed (2). The total score ranges from 0 to 30
Change in pulmonary function as assessed by spirometry Baseline at Weeks 28 and 56 Forced vital capacity (FVC) and Forced expiratory volume in 1 second (FEV1) and the ratio of FEV1/FVC will be determined by spirometry.
Change in disease severity as assessed by the Patient Global Impression of Severity (PGIS) Baseline to Weeks 28 and 56 PGIS is a single item, self-administered questionnaire to assess the patient's global impression of severity
Change in disease severity as assessed by the Patient's Global Impression of Change (PGIC) At Weeks 28 and 56 PGIC is a single item, self-administered questionnaire to assess the patient's global impression of change
Change in disease severity as assessed by the Clinician's Global Impression of Change (CGIC) At Weeks 28 and 56 CGIC is a single-item questionnaire to assess the clinician's global impression of change
Concentration of total activin A in serum over time Through Week 56
Trial Locations
- Locations (22)
Hôpital Lapeyronie
🇫🇷Montpellier, France
Kyushu University Hospital
🇯🇵Fukuoka, Japan
Hospital Israelita Albert Einstein
🇧🇷Sao Paulo, Brazil
HUS Children and Adolescents Park Hospital Clinical Trial Unit
🇫🇮Helsinki, Stenbäckinkatu 11, Finland
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Szpital Centrum Medyczne Medyk
🇵🇱Rzeszow, Podkarpackie, Poland
University of California Los Angeles (UCLA) Medical Center
🇺🇸Los Angeles, California, United States
Royal North Shore Hospital
🇦🇺St Leonards, New South Wales, Australia
Hopital Lariboisiere
🇫🇷Paris, France
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
IRCCS Istituto Giannina Gaslini
🇮🇹Genoa, Italy
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Oita University Hospital
🇯🇵Yufu, Oita, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Amsterdam University Medical Center
🇳🇱Amsterdam, North Holland, Netherlands
Clinica Universidad de La Sabana
🇨🇴Chia, Cundinamarca, Colombia
Universidad de Concepcion
🇨🇱Concepcion, Bio Bio, Chile
Hospital Kuala Lampur
🇲🇾Kuala Lumpur, Malaysia
Tongji Hospital of Tongji University
🇨🇳Shanghai, China
Royal National Orthropaedic Hospital NHS Trust
🇬🇧Middlesex, Greater London, United Kingdom
University of Cape Town
🇿🇦Rondebosch, Cape Town, South Africa