Palovarotene for patients with multiple hereditary exostosis: results of MO-Ped, a terminated, randomized, placebo-controlled, double-blind phase 2 trial.

A phase II trial (MO-Ped; NCT03442985) assessed palovarotene in pediatric patients with multiple hereditary exostosis (MHE). Patients aged ≤ 14 years with MHE were randomized 1:1:1 to placebo, palovarotene 2.5 mg, or palovarotene 5.0 mg daily. Due to concerns of premature physeal closure (PPC), a partial clinical hold was instituted, followed by trial termination. The primary efficacy endpoint was the annualized rate of new osteochondromas (OCs). Safety was assessed. Overall, 193 patients received ≥ 1 dose of palovarotene or placebo. Due to trial termination, no patients completed planned treatment. Prior to 06 December 2019 (patients notified of clinical hold and treatment stopped), 30 patients completed Month 12 efficacy imaging. No significant differences in the annualized rate of new OCs, or change from baseline in volume of OCs or OC cartilage, were observed between treatment groups. The adverse event profile was consistent with systemic retinoids. There was no evidence of an effect of palovarotene on linear growth and no cases of PPC. Overall, palovarotene showed no clear efficacy signal in MHE, resulting in a non-favorable benefit-risk profile. Interpretation of results was limited by the reduced treatment duration and smaller than expected cohort. The trial yielded important data on the natural history of MHE.Trial registration: NCT03442985 (first posted 22 February 2018).