An Efficacy and Safety Study of Palovarotene for the Treatment of MO
Condition: Exostoses, Multiple Hereditary
MeSH terms: Osteochondroma; Exostoses, Multiple Hereditary; Osteochondromatosis; Exostoses; Osteophyte
Intervention: Palovarotene 2.5 mg; Palovarotene 5.0 mg; Placebo
Intervention description: Subjects received a weight-adjusted dose equivalent of 2.5 mg palovarotene, once daily, for up to 24 months.; Subjects received a weight-adjusted dose equivalent of 5.0 mg palovarotene, once daily, for up to 24 months.; Subjects received placebo, once daily, for up to 24 months.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Multicenter, randomized, double-blind, placebo-controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 193.0
Sex: All
Minimum age: 2 Years
Maximum age: 14 Years
Healthy volunteers: No
Keywords: Multiple osteochondromas; Osteochondroma; Palovarotene; Hereditary multiple exostoses; HME; MO; Retinoic acid receptor gamma agonist; Retinoic acid receptor agonist

Summary:

      This is a randomized, double-blind, placebo-controlled study comparing the safety and
      efficacy of 2 dosage regimens of palovarotene versus placebo in preventing disease
      progression in pediatric subjects with multiple osteochondromas (MO).
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Written, signed, and dated informed subject/parent consent and age-appropriate assent
             (performed according to local regulations).

          -  A clinical diagnosis of MO with disease-causing exostosin 1 or 2 gene mutations.

          -  Male or female from 2 to 14 years of age.

          -  Female subjects must be premenarchal at screening.

          -  A bone age at screening of 14 years or less.

          -  Symptomatic MO, defined as five or more clinically evident osteochondromas and a new
             or enlarged osteochondroma that occurred in the preceding 12 months, five or more
             clinically evident osteochondromas and the presence of a painful osteochondroma, a
             skeletal deformity, a joint limitation, or prior surgery for a MO-related
             complication.

          -  The ability to undergo whole body MRI with or without sedation/general anesthesia.

          -  Use of two effective methods of birth control during treatment, and for 1 month after
             treatment discontinuation, unless committed to true abstinence from heterosexual sex.
             Sexually active females of child-bearing potential must also agree to start effective
             methods of birth control at screening.

        Key Exclusion Criteria:

          -  Weight under 10 kg.

          -  Other syndromic conditions such as Langer-Giedion or Potocki-Shaffer.

          -  Any subject with neurologic signs suggestive of spinal cord impingement.

          -  Concomitant medications that are strong inhibitors or inducers of cytochrome P450 3A4
             activity.

          -  Amylase or lipase >2 times the above the upper limit of normal (>2×ULN) or with a
             history of chronic pancreatitis.

          -  Elevated aspartate aminotransferase or alanine aminotransferase above 2.5×ULN.

          -  Any surgical implant that is contraindicated for MRI.