A Phase 2, Randomized, Double-Blind, Placebo-Controlled Efficacy andSafety Study of Palovarotene in Subjects with Multiple Osteochondromas
- Conditions
- Multiple Osteochondromas (MO)MedDRA version: 20.0Level: SOCClassification code 10010331Term: Congenital, familial and genetic disordersSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Musculoskeletal Diseases [C05]
- Registration Number
- EUCTR2017-002751-28-IT
- Lead Sponsor
- CLEMENTIA PHARMACEUTICALS INC.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 240
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 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 assessed by a central reader.
6.Symptomatic MO, defined as the occurrence of any one of the following at screening:
•A new or enlarged OC in the preceding 12 months.
•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 cannot be screened until 8 weeks post-surgery to allow for stabilization of symptoms. 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, <20% variance) for 2 weeks prior to screening.
9.The ability to undergo whole body MRI without general anesthesia requiring intubation.
10.Male and female subjects with a Tanner stage of =2 must agree to use two highly effective methods of birth control during treatment, and for 1 month after treatment discontinuation, unless they commit to true abstinence from heterosexual contact. Sexually active FOCBP must also agree to start effective methods of birth control at screening.
11.Subjects must be accessible for treatment with study drug and follow-up.
Are the trial subjects under 18? yes
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.A weight <10 kg.
2.Other known syndromic conditions such as Langer-Giedion or Potocki Shaffer syndromes.
3.Any subject with neurologic signs suggestive of spinal cord impingement.
4.If subject is currently using vitamin A or beta carotene, multivitamins containing vitamin A or beta carotene, or herbal preparations, fish oil, and unable or unwilling to discontinue use of these products during palovarotene treatment. For eligibility, no washout is required prior to the first dose of study drug.
5.Exposure to synthetic oral retinoids within 4 weeks prior to enrollment.
6.Concurrent treatment with tetracycline or any tetracycline derivatives, due to the potential increased risk of pseudotumor cerebri.
7.History of allergy or hypersensitivity to retinoids, gelatin, or lactose (other than lactose intolerance).
8.Concomitant medications that are strong inhibitors or inducers of cytochrome P450 (CYP450) 3A4 activity.
9.Amylase or lipase >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.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method