Multiple Osteochondromas (MO) MedDRA version: 20.0 Level: PT Classification code 10079019 Term: Hereditary multiple osteochondromas System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Clementia Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written, signed, and dated informed subject/parent consent and age appropriate assent (performed according to local regulations). 2. A clinical diagnosis of MO with a disease-causing Ext1 or Ext2 mutations confirmed by a central laboratory. 3. Male and female subjects with a chronological age of 2-14 years, inclusive. 4. Female subjects must be premenarchal at screening. 5. Bone age at screening of =14 years, 0 months per the Greulich-Pyle method as assesed by a central reader. 6. Symptomatic MO, defined as the occurrence of any one of the following at screening: • Five or more clinically-evident OCs and the presence of a new or enlarging OC in the preceding 12 months. • Five or more clinically-evident OCs and the presence of a painful OC. • A skeletal deformity. • A joint limitation. • Prior surgery for a MO-related complication. 7. If a subject had a prior surgery for MO, the subject should not be screened until at least 8 weeks post-surgery to allow for at least 12 weeks of stabilization of symptoms prior to first dose. Surgical orthopedic implants are allowed if they were in situ for =12 weeks prior to the baseline MRI 8. If a subject is currently receiving pain medications, the dose must be stable (ie, =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. A weight 2 times the above the upper limit of normal (>2×ULN) or with a history of chronic pancreatitis. 10. Elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5x ULN. 11. Fasting triglycerides >400 mg/dL with or without therapy. 12. Subjects with uncontrolled cardiovascular, renal, hepatic, pulmonary, gastrointestinal, endocrine, metabolic, ophthalmologic, immunologic, psychiatric, or other significant disease. These include subjects requiring glucocorticoid at doses >0.2mg/kg or up to 10 mg prednisone equivalent daily. 13. Subjects experiencing suicidal ideation (type 4 or 5) or any suicidal behavior within the past month or any suicidal behavior within the past year as defined by the Columbia-Suicide Severity Rating Scale (C SSRS). 14. Subjects unable or unwilling to complete the study or all study-related procedures, including imaging. 15. Any surgical implant that is contraindicated for MRI. Dental braces are permitted. 16. Participation in any clinical research study within 4 weeks prior to enrollment or simultaneous participation in any clinical research study. 17. 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 two dosage regimens of palovarotene compared with placebo in preventing new osteochondromas (OCs) in subjects with multiple osteochondromas (MO) due to exostosin 1 (Ext1) or exostosin 2 (Ext2) mutations.;Secondary Objective: To compare the following effects of palovarotene with placebo: - The volume of osteochondromas (OCs) as assessed by magnetic resonance imaging (MRI). - The proportion of subjects with no new (OCs). - The rate of new or worsening skeletal deformities. - The rate of MO-related surgeries Additional secondary objectives: - Overall palovarotene safety. - The pharmacokinetics of palovarotene at steady state. - The palatability of drug product when sprinkled onto specific foods. Exploratory Objective: To compare the following effects of palovarotene with placebo: - The change in volume of OC cartilage caps as assessed by MRI. - The rate of new or worsening functional limitations. - Pain and pain interference due to OCs. - Quality of life. ;Primary end point(s): The primary efficacy endpoint will compare palovarotene with placebo on the annualized rate of new OCs as assessed by whole body MRI.;Timepoint(s) of evaluation of this end point: At month 12 and month 24. Whole body MRIs and upper/lower limb radiographs will be performed every 12 months. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints will compare palovarotene with placebo on the following: - The change from baseline in the total volume of OCs as assessed by whole body MRI at Months 12 and 24. - The proportion of subjects with no new OCs as assessed by whole body MRI at Months 12 and 24. - The annualized rate of new or worsening deformities as assessed by radiographic imaging of both upper and lower limbs. - The annualized rate of MO-related surgeries. Surgeries include any procedure indicated for the treatment of MO, such as an excision of a symptomatic OC or correction of a limb deformity. ;Timepoint(s) of evaluation of this end point: At Months 12 and 24. Whole body MRIs will be performed every 12 months. | — |
Countries
Australia, Belgium, Canada, France, Italy, Japan, Netherlands, Portugal, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactClinical Trials Information
Clementia Pharmaceuticals Inc.
Outcome results
None listed