ESPE Abstracts

Introduction: Hypochondroplasia is a rare genetic growth-related condition primarily caused by FGFR3 variants that lead to decreased endochondral bone growth, disproportionate short stature and other medical complications. It shares pathogenetic and phenotypic similarities to achondroplasia. Outside of Japan, there are no approved pharmacological treatments for hypochondroplasia. Vosoritide, a C-type natriuretic peptide analog, is an approved first-in-class targeted treatment for achondroplasia and is now under investigation for its potential in hypochondroplasia. Here, we report the design of Study 111-902 (NCT06212947), a non-interventional study designed to generate natural history data for hypochondroplasia, as well as baseline growth data to support interventional studies of vosoritide in this condition.

Methods: Study 111-902 is a multicenter, multinational, observational study that aims to characterize the clinical course and growth in children with genetically confirmed hypochondroplasia by collecting prospective and retrospective serial anthropometric measures in pediatric participants aged ≤15 years. Prospective growth data will be collected for a minimum of 6 months. Retrospective data extraction will provide additional historic growth data and information on frequency of specific medical events. The primary objective is to assess growth over time in children with hypochondroplasia by sex across ages. Outcome measures include annualized growth velocity, height, height Z-score, body mass index, and ratios of upper to lower body segments and extremities. The secondary objectives include evaluation of the impact of hypochondroplasia on health-related quality of life, and assessment of the frequency, event-rate and burden of medical events, interventions and procedures. In consenting participants, the association between genomic variants and outcomes such as growth and final adult height (FAH) will be also explored. This study plans to enroll approximately 400 participants. While no investigational product will be administered during the study, eligible participants will have the option to enroll in future interventional studies with vosoritide following at least 6 months of growth data collection. The maximum study duration for participants is defined by achievement of FAH.

Results: The protocol is registered on ClinicalTrials.gov (NCT06212947). In total, 11 countries and 43 sites are involved. Further data will be shared on the number and demographics of participants enrolled.

Conclusion: Study 111-902 will collect global long-term growth data and provide important insights into the clinical manifestations and course of hypochondroplasia in children. Prospective growth data collected in this study will permit participants to enter future interventional studies of vosoritide in hypochondroplasia.