A phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of vosoritide in children with hypochondroplasia: CANOPY HCH-3 study design.

BACKGROUND: Hypochondroplasia is a skeletal dysplasia characterized by disproportionate short stature that is caused by gain-of-function variants in the fibroblast growth factor receptor 3 gene (FGFR3), which negatively regulates endochondral bone growth. Current treatments are based on symptom management; there are no treatments targeting the signaling pathways that underlie hypochondroplasia. Vosoritide, a C-type natriuretic peptide analog that counteracts overactive FGFR3 signaling to stimulate endochondral bone growth, is approved for the treatment of achondroplasia in children. A phase 1/2 clinical trial demonstrated that vosoritide treatment for 1 year increased growth in children with hypochondroplasia and was well-tolerated. OBJECTIVES: The objectives of CANOPY HCH-3 are to evaluate the efficacy and safety of vosoritide for the treatment of hypochondroplasia in children. DESIGN: CANOPY HCH-3 was a phase 3, randomized, double-blind, placebo-controlled, multicenter study. METHODS AND ANALYSIS: Children aged ≥3 to <18 years with confirmed hypochondroplasia who had ≥6 months of pre-treatment standing height from a prior observational study before randomization were enrolled. Participants were randomized to receive 52 weeks of daily treatment with vosoritide or placebo, followed by 2 weeks of safety follow-up. The primary endpoint is change from baseline in annualized growth velocity at week 52 versus placebo. ETHICS: CANOPY HCH-3 was conducted in accordance with the Council for International Organizations of Medical Sciences International Ethical Guidelines, the principles of the Declaration of Helsinki and of Good Clinical Practice, and applicable laws and regulations. Protocols were approved by relevant local health authorities, ethics committees, and institutions. Written informed consent from the participant, or parent or legal guardian, was obtained prior to any study-related procedures being performed. DISCUSSION: CANOPY HCH-3 will provide further evidence for the efficacy and safety of vosoritide in children with hypochondroplasia.