Fibrodysplasia Ossificans Progressiva
Conditions
Keywords
Heterotopic Ossification (HO) Lesions, Type I activin A receptor (ACVR1), Optima, LUMINA-1, Flare-Ups
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)
Interventions
DRUGGaretosmab
Garetosmab is supplied as a liquid drug product and will be administered IV.
DRUGPlacebo
Placebo to match garetosmab, is supplied as a liquid solution without the monoclonal antibody (or the protein) and is administered IV.
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 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
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 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 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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 Treatment |
| Occurrence of new HO lesions | At Weeks 28, 56 and 84 | Reported as Yes/No Week 84 Only for Patients on Extended Treatment |
| Total 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 Treatment |
| Number 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 | — |
| 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 | — |
Countries
Australia, Brazil, Chile, China, Colombia, Finland, France, Hong Kong, Italy, Japan, Malaysia, Netherlands, Poland, South Africa, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed