Comparative Study of Somapacitan and Somatropin on Growth Outcomes in Pediatric Growth Hormone Deficiency

The primary objective of this clinical trial is to compare the effect of **somapacitan** versus Norditropin® on longitudinal growth in children with **growth hormone deficiency**. This objective is clinically relevant as it aims to evaluate the efficacy of a once-weekly dosing regimen of somapacitan compared to the daily administration of Norditropin®, potentially offering a more convenient treatment option for pediatric patients.

Secondary objectives include comparing the safety profile of somapacitan versus Norditropin® in the same patient population. Assessing safety is crucial to ensure that the therapeutic benefits of somapacitan do not come at the expense of increased adverse effects, thereby supporting informed clinical decision-making regarding its use in children with growth hormone deficiency.

The clinical trial involves a total of **178 participants** diagnosed with **Growth Hormone Deficiency in children**. The study population comprises both male and female prepubertal children, with boys aged between 2 years and 26 weeks to less than 11 years, and girls aged between 2 years and 26 weeks to less than 10 years. Participants were selected based on specific criteria, including a confirmed diagnosis of growth hormone deficiency, impaired height and height velocity, and no prior exposure to growth hormone therapy or Insulin-like Growth Factor-I treatment. The trial population is characterized by a vulnerable group, with participants having an impaired height defined as at least 2.0 standard deviations below the mean height for their chronological age and gender. Additionally, lifestyle factors such as diet and physical activity were not specified as part of the selection criteria. The study aims to compare the effect of somapacitan versus Norditropin® on longitudinal growth in this specific pediatric population.

The clinical trial is designed to evaluate the efficacy and safety of **somapacitan** administered once weekly compared to daily administration of Norditropin® in children diagnosed with **growth hormone deficiency**. This is a randomized, double-blind, controlled trial with a primary objective to assess the impact on longitudinal growth. The trial is expected to span approximately 312 weeks, with participant involvement lasting up to 208 weeks. The study includes a series of visits, starting with an inclusion (screening) visit to confirm eligibility based on criteria such as age, confirmed diagnosis, and growth parameters. Participants will undergo regular follow-up visits to monitor growth velocity, bone age, and other safety and pharmacodynamic endpoints. The end-of-study visit will conclude the participant's involvement, assessing the primary and secondary endpoints.

Participants will be randomly assigned to receive either somapacitan or Norditropin® using a pre-filled pen-injector for subcutaneous administration. The trial will employ a double-blind methodology to ensure unbiased results. The primary endpoint is the change in height velocity from baseline to week 52, while secondary endpoints include changes in bone age, height standard deviation score, and various safety parameters such as fasting plasma glucose and glycated hemoglobin levels. The trial will also assess pharmacodynamic changes in insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) standard deviation scores.

Participants may be withdrawn from the study if they experience adverse events, fail to comply with the study protocol, or if the investigator deems it necessary for safety reasons. The trial is conducted in compliance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants. The study's estimated end date is September 30, 2025, with recruitment having commenced on June 18, 2019. The trial's design and procedures are structured to provide robust data on the comparative effectiveness of the two treatment regimens in managing growth hormone deficiency in children.

The clinical trial involves the administration of **Sogroya**, a solution for injection containing the active substance **somapacitan**. This medication is provided in three different dosages: 5 mg/1.5 mL, 10 mg/1.5 mL, and 15 mg/1.5 mL, all formulated as a solution for injection in pre-filled pens. The pharmaceutical form is a **solution for injection**, and the route of administration is **subcutaneous**. The dosing schedule for Sogroya is once weekly, with the maximum treatment period extending up to 312 weeks. The administration device used is the PDS290 pen-injector, a disposable, pre-filled, multi-dose pen-injector, which allows for precise dosing increments specific to the variant of somapacitan used. Participant compliance is monitored through regular assessments of dosing adherence and injection technique.

The comparator treatment in this trial is **Norditropin FlexPro**, which contains the active substance **somatropin**. This medication is also provided as a solution for injection in a pre-filled pen, specifically designed for subcutaneous administration. The Norditropin FlexPro pen-injector is a disposable, pre-filled, multi-dose device. The dosing schedule for Norditropin is daily, with a maximum treatment period of 52 weeks. Compliance with the dosing regimen is monitored through participant logs and regular follow-up visits to ensure adherence to the daily administration schedule.

Both treatments are manufactured by Novo Nordisk A/S and are not formulated for pediatric use. The trial aims to compare the effect and safety of once-weekly dosing of somapacitan with daily Norditropin in children with growth hormone deficiency, focusing on longitudinal growth outcomes. The trial does not include any placebo or additional non-experimental treatments. All medications are administered under the supervision of clinical trial personnel to ensure proper dosing and participant safety.

The efficacy of the clinical trial comparing the effect and safety of once-weekly dosing of **somapacitan** with daily Norditropin® in children with growth hormone deficiency will be assessed using several primary and secondary endpoints. The primary endpoint is the height velocity, measured in centimeters per year, from baseline (week 0) to visit 7 (week 52). Secondary endpoints include changes in bone age, height standard deviation score (SDS), and height velocity SDS, all evaluated from baseline to visit 7 (week 52). Additionally, pharmacodynamic endpoints such as changes in Insulin-like Growth Factor-I (IGF-I) SDS and IGFBP-3 SDS will be measured from baseline to various timepoints, including weeks 52, 104, 156, and 208.

Safety endpoints will also be assessed, including changes in fasting plasma glucose, homeostatic model assessment (HOMA), and Glycated hemoglobin (HbA1c) at multiple timepoints from screening to weeks 52, 104, 156, and 208. These efficacy and safety parameters will be collected and analyzed using validated laboratory tests and patient-reported outcomes, ensuring a comprehensive evaluation of the treatment's impact on growth hormone deficiency in the pediatric population. The trial is designed to provide robust data on the longitudinal growth effects of somapacitan compared to Norditropin® over a treatment period of up to 312 weeks.