Phase 2/3 Study of BMN 333 Versus Vosoritide in Children With Achondroplasia

The primary objective of this study is to evaluate the efficacy of BMN 333 compared to vosoritide in pediatric patients with achondroplasia. The evaluation focuses on the impact of three different doses during Phase 2 and the effect of a selected dose during Phase 3 on annualized growth velocity (AGV) after 52 weeks of treatment.

The secondary objectives include:

• Assessment of the effect of three doses of BMN 333 versus vosoritide on growth parameters.
• Evaluation of the safety and tolerability of the three doses of BMN 333.
• Investigation of the effect of BMN 333 versus vosoritide on additional growth parameters following 52 weeks of treatment in Phase 3.

This clinical trial involves a total of 160 participants diagnosed with achondroplasia. The study population consists of both male and female patients who are considered a vulnerable group. For the Phase 2 portion of the study, participants must be aged between 2 and 11 years, while the Phase 3 portion includes individuals aged between 2 and 18 years. Inclusion requires documented genetic confirmation of the condition and the presence of open epiphyses as assessed via standard radiographic methods. Eligible participants must have a body weight of at least 8.0 kg and be ambulatory. Depending on the study phase, participants must also meet specific Tanner stage requirements. Female participants of a certain age or those who have commenced menses must demonstrate a negative pregnancy test. The study requires that caregivers are capable and willing to undergo training for the administration of injections.

This multicenter, randomized, operationally seamless Phase 2/3 study is designed to evaluate the efficacy and safety of BMN 333 compared to vosoritide in children with achondroplasia. The research methodology incorporates two distinct phases. In Phase 2, the study aims to evaluate the effect of three doses of BMN 333 versus vosoritide on annualized growth velocity (AGV) via an interim analysis. In Phase 3, the study evaluates the effect of BMN 333 at a selected dose versus vosoritide on AGV after 52 weeks of treatment. The primary endpoint for Phase 2 is the predicted AGV at week 52, whereas the primary endpoint for Phase 3 is the AGV at week 52. Following a screening visit to confirm eligibility through genetic testing, assessment of open epiphyses, and measurement of body weight, participants will receive subcutaneous administration of the study products. The study involves periodic monitoring of secondary endpoints, including changes in standing height, height Z-score, and upper to lower body segment ratio. Participants are expected to undergo treatment for a duration of 52 weeks. The total study period is estimated to conclude in June 2029.

The experimental treatment consists of BMN 333, which is provided as a powder for solution for injection. This substance is administered via subcutaneous use.

The comparator treatment involves vosoritide, administered as a solution for injection through subcutaneous use. Two specific formulations are utilized: Voxzogo 0.56 mg powder and solvent for solution for injection at a dose of 0.40 mg and Voxzogo 1.2 mg powder and solvent for solution for injection at a dose of 0.80 mg. This medication is classified as an orphan drug.

The efficacy of BMN 333 in children with achondroplasia will be assessed through specific primary and secondary endpoints across two phases. In Phase 2, the primary endpoint is the predicted annualized growth velocity (AGV) at Week 52, derived from cumulative data collected at Weeks 26, 39, and 52. Secondary efficacy parameters for Phase 2 include AGV at Weeks 26 and 52, as well as the change from baseline in standing height, height Z-score, and upper to lower body segment ratio at Weeks 26 and 52.

In Phase 3, the primary endpoint is the AGV at Week 52. Secondary efficacy assessments for Phase 3 consist of the change from baseline in standing height, height Z-score, and upper to lower body segment ratio at Week 52.