Efficacy and Safety of Lonapegsomatropin Versus Somatropin in Children and Adolescents with Growth Failure or Short Stature Due to GH-Sufficient Disorders

The primary objective of this study is to evaluate the efficacy of lonapegsomatropin compared to somatropin in children and adolescents presenting with short stature or growth failure due to growth hormone sufficient disorders, including Turner syndrome, SHOX deficiency, small for gestational age, and idiopathic short stature. 5

The secondary objectives include:

• Evaluation of additional measures of efficacy in the studied pediatric population. 5
• Assessment of the safety and tolerability of lonapegsomatrin. 4

This study involves 120 participants, including both male and female patients. The study population consists of children and adolescents, aged between 2 and <18 years, who are prepubertal. Participants are selected based on a diagnosis of Turner Syndrome, short stature homeobox containing gene deficiency, small for gestational age, or idiopathic short stature. Key inclusion requirements include being naïve to growth hormone and growth hormone promoting therapies, alongside documented impaired growth or short stature according to specific clinical and genetic criteria. The objectives are:

• To evaluate the efficacy of lonapegsomatropin as compared to somatropin.

This Phase 3, open-label, randomized, parallel-arm, active-controlled, multicenter basket trial is designed to evaluate the efficacy and safety of lonapegsomatropin compared to daily somatropin. The study focuses on prepubertal children and adolescents with growth failure or short stature resulting from growth hormone sufficient disorders, specifically Turner Syndrome, SHOX deficiency, small for gestational age, or idiopathic short stature. Following a screening visit to confirm eligibility, participants are assigned to receive either once-weekly subcutaneous lonapegsomatropin or daily subcutaneous somatropin. The primary endpoint is the annualized height velocity assessed at Week 52, with additional secondary endpoints including height SDS changes and bone age assessments at Week 104. The total study duration and participant involvement extend through the follow-up period, with the trial estimated to conclude by April 2029.

Lonapegsomatropin is administered as a powder and solvent for solution for injection via the subcutaneous route. The dosage is specified as 00 mg/kg.

Somatropin, provided as Norditropin FlexPro in a solution for injection, serves as the comparator treatment. This medication is administered via subcutaneous injection at a dosage of 00 mg/kg.

The primary efficacy endpoint for this clinical trial is the annualized height velocity (AHV) assessed at Week 52. Secondary efficacy parameters include the AHV at Week 104 and the change from baseline in height SDS, utilizing both CDC-based and condition-specific metrics at Weeks 52 and 104. Additionally, bone age and the bone age to chronological age ratio will be evaluated at Weeks 52 and 104.