Phase 3 Randomized, Placebo-Controlled Study to Assess Safety, Tolerability, and Efficacy of Garetosmab in Patients with Fibrodysplasia Ossificans Progressiva
- Conditions
- uiterst zeldzame genetische bindweefselaandoeningverbening10005959
- Registration Number
- NL-OMON53784
- Lead Sponsor
- Regeneron Pharmaceuticals Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 6
1. Male or female 18 years or older at screening
2. 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)]
3. Confirmation of FOP diagnosis with documentation of Type I activin A
receptor (ACVR1) FOP causing mutation
4. 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
5. Willing and able to undergo CT imaging procedures and other procedures as
defined in the protocol
6. Willing and able to comply with clinic visits and study-related procedures
7. Provide informed consent signed by study patient or legally acceptable
representative
8. Able to understand study-related questionnaires
A patient who meets any of the following criteria will be excluded from the
study:
1. CAJIS score at screening >19
2. 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
3. Previous history or diagnosis of cancer (exceptions: localized
basal/squamous cell cancer
that has been successfully excised; in situ cervical cancer)
4. Severely impaired renal function defined as estimated glomerular filtration
rate <30 mL/min/1.73 m^2 calculated by the Modification of Diet in Renal
Disease equation
(1 retest is allowed)
5. Uncontrolled diabetes defined as hemoglobin A1C (HbA1c) >9% at screening (1
retest is allowed)
6. History of poorly controlled hypertension, as defined by:
a. Systolic blood pressure >=180 mm Hg or diastolic blood pressure >=110 mm Hg at
the screening visit
b. 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 [hemorrhages or exudates, papilledema])
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 (Note: sinus dysrhythmia,
asymptomatic block or well-controlled atrial fibrillation with normal resting
ventricular rate are not exclusion criteria.)
9. History of severe anemia requiring transfusion
10. Patients who are on concomitant antiplatelet therapy (eg, clopidogrel),
anticoagulants (eg, warfarin, heparin, factor Xa inhibitor, or thrombin
inhibitors) in the last 30 days or within 5 half-lives of the therapy,
whichever is longer. Low-dose acetylsalicylic acid (aspirin <=100 mg or <=150
mg/day, based on local practice) is acceptable.
(NOTE: low doses of heparin for flushing of catheters will be permitted.)
11. Patients with a history of severe, non-traumatic bleeding requiring
transfusion or hospitalization for hemodynamic compromise (eg, severe nose
bleeds requiring hospitalization, nasal packing or cauterization, menstrual
bleeding that is prolonged/heavy)
12. Patients with a known pre-existing medical history of a bleeding diathesis
(eg, hemophilia A, von Willebrand*s Factor deficiency, platelet count <=20×10^9/
L)
13. Ongoing significant viral illness or pneumonia within 2 weeks of screening
14. 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
15. Known history of recent epididymitis (within 6 months of screening) or
sexually transmitted
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary Efficacy Endpoint:<br /><br>The primary efficacy endpoint is the number of new HO lesions adjudicated as<br /><br>positive based on CT at week 56.<br /><br>Primary Safety Endpoint:<br /><br>The primary safety endpoint is the incidence and severity of treatment emergent<br /><br>adverse<br /><br>events of special interest (AESIs) from baseline to week 56.<br /><br></p><br>
- Secondary Outcome Measures
Name Time Method