Fibrodysplasia Ossificans Progressiva (FOP) MedDRA version: 20.0 Level: PT Classification code 10068715 Term: Fibrodysplasia ossificans progressiva System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Interventions
Product Name: PALOVAROTENE
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PALOVAROTENE
CAS Number: 410528-02-8
Other descriptive name: PALOVAROTENE
Concentration unit: mg milligram(s)
Concent
Sponsors
Clementia Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects must meet all of the following criteria to be eligible for enrollment: 1. Written, signed, and dated informed subject/parent consent; and for subjects who are minors, age-appropriate assent (performed according to local regulations). 2. Male or female at least 4 years of age. 3. Clinically diagnosed with FOP, with the R206H ACVR1 mutation. 4. No flare-up symptoms within the past 4 weeks, including at the time of enrollment. 5. Females of child-bearing potential must have a negative blood or urine pregnancy test (with sensitivity of at least 50 mIU/mL) prior to administration of palovarotene. Male and FOCBP subjects must agree to remain abstinent during treatment and for 1 month after treatment or, if sexually active, to use two highly effective methods of birth control during and for 1 month after treatment. Additionally, sexually active FOCBP subjects must already be using two highly effective methods of birth control 1 month before treatment is to start. Specific risk of the use of retinoids during pregnancy, and the agreement to remain abstinent or use two highly effective methods of birth control will be clearly defined in the informed consent and the subject or legally authorized representatives (eg, parents, caregivers, or legal guardians) must specifically sign this section. 6. Must be accessible for treatment and follow-up, and be able to undergo all study procedures. Subjects living at distant locations from the investigational site must be able and willing to travel to a site for the initial and all on-site follow-up visits. Subjects must be able to undergo low-dose, WBCT (excluding head). Are the trial subjects under 18? yes Number of subjects for this age range: 20 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 60 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria are not eligible for enrollment: 1. Weight 2x above the upper limit of normal (ULN) or with a history of chronic pancreatitis. 8. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x ULN. 9. Fasting triglycerides >400 mg/dL with or without therapy. 10. Female subjects who are breastfeeding. 11. Subjects with uncontrolled cardiovascular, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease. 12. Subjects experiencing suicidal ideation (type 4 or 5) or any suicidal behavior within the past month as defined by the Columbia-Suicide Severity Rating Scale (C-SSRS). 13. Simultaneous participation in another clinical research study within 4 weeks prior to Screening; or within five half-lives of the investigational agent, whichever is longer. 14. Any reason that, in the opinion of the Investigator, would lead to the inability of the subject and/or family to comply with the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the efficacy of palovarotene in decreasing heterotopic ossification (HO) in adult and pediatric subjects with FOP as assessed by low-dose, whole body computed tomography (WBCT), excluding head, as compared to untreated subjects from Clementia’s FOP natural history study. • To evaluate the safety of palovarotene in adult and pediatric subjects with FOP.;Secondary Objective: • To evaluate the effect of palovarotene on flare-up rate and proportion of subjects reporting at least one flare-up. • To evaluate the effect of palovarotene on range of motion (ROM) as assessed by the Cumulative Analogue Joint Involvement Scale for FOP (CAJIS). • To evaluate the effect of palovarotene on physical function using age-appropriate forms of the FOP-Physical Function Questionnaire (FOP-PFQ). • To evaluate the effect of palovarotene on physical and mental health using age-appropriate forms of the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale. • To evaluate the pharmacokinetics of palovarotene.;Primary end point(s): The annualized change in new HO volume as assessed by low-dose, WBCT (excluding head) compared to untreated subjects from the NHS.;Timepoint(s) of evaluation of this end point: Month 6, 12, 18 and 24 months. It will also being evaluated at End of trial or End of study visit. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The proportion of subjects with any new HO. 2. The change from baseline in the number of body regions with new HO. 3. The proportion of subjects reporting flare-ups. 4. The flare-up rate per subject-month exposure.;Timepoint(s) of evaluation of this end point: Month 6, 12, 18 and 24 months. It will also being evaluated at End of trial or End of study visit. | — |
Countries
Argentina, Australia, Brazil, Canada, France, Germany, Italy, Japan, Netherlands, Russian Federation, South Africa, Spain, Sweden, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Clementia Pharmaceuticals Inc.
Outcome results
None listed