A Comparative Study of Somapacitan and Somatropin in Pediatric Patients with Short Stature Due to SGA, Turner Syndrome, Noonan Syndrome, or Idiopathic Short Stature

The primary objective of this study is to confirm the non-inferiority of once-weekly somapacitan compared with once-daily Norditropin® in terms of longitudinal growth, specifically measured by height velocity at week 52, in children with short stature due to being born small for gestational age (SGA), Turner syndrome (TS), Noonan syndrome (NS), or idiopathic short stature (ISS). This is clinically relevant as it aims to establish an effective and potentially more convenient dosing regimen for growth hormone therapy in these pediatric populations. Secondary objectives include:

• Evaluating once-weekly somapacitan compared with once-daily Norditropin® in terms of other aspects of longitudinal growth in children with each of the four indications: SGA, TS, NS, or ISS.
• Assessing the safety of once-weekly somapacitan compared with once-daily Norditropin® in terms of safety parameters measured by glucose metabolism in children with each of the four indications.
• Evaluating the steady state pharmacokinetics of once-weekly somapacitan in children with each of the four indications.
• Assessing the long-term safety of once-weekly somapacitan in terms of safety parameters measured by glucose metabolism in children with each of the four indications.

These secondary objectives are crucial for understanding the broader implications of somapacitan use, including its safety profile and pharmacokinetic properties, which are essential for optimizing treatment strategies in pediatric endocrinology.

The clinical trial involves a total of 277 participants who are children with short stature due to being born small for gestational age, or having Turner syndrome, Noonan syndrome, or idiopathic short stature. The study population includes both male and female prepubertal children, with boys aged between 2 years and 26 weeks to below 11 years, and girls aged between 2 years and 26 weeks to below 10 years. Participants were selected based on specific criteria, including no prior exposure to growth-promoting therapies. The trial population is considered vulnerable due to the young age of the participants. The study does not specify any particular lifestyle considerations such as diet or physical activity. Key inclusion criteria include specific age and developmental stages, such as Tanner stage 1 for breast development in girls and testis volume below 4 mL in boys, ensuring the participants are prepubertal. The trial aims to assess the efficacy of once-weekly somapacitan compared to once-daily Norditropin® in promoting longitudinal growth over a 52-week period.

The clinical trial is designed to evaluate the efficacy and safety of somapacitan, administered once weekly, compared to daily administration of Norditropin® in children with short stature due to being born small for gestational age, Turner syndrome, Noonan syndrome, or idiopathic short stature. This is a randomized, double-blind, controlled trial with a basket study design. The trial aims to confirm the non-inferiority of somapacitan in terms of longitudinal growth, measured by height velocity at week 52. The trial is expected to conclude by June 16, 2027, with recruitment having started on September 5, 2022. Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on specific criteria, such as no prior exposure to growth-promoting therapies. The trial includes regular follow-up visits to monitor growth parameters and safety outcomes, with the primary endpoint being height velocity. Secondary endpoints include changes in height SDS, bone age, and various metabolic parameters. The end-of-study visit will occur at the conclusion of the treatment period, which is up to 156 weeks for somapacitan and 52 weeks for Norditropin®. The expected length of participant involvement is determined by the treatment period, with somapacitan administered for up to 156 weeks. Conditions that may lead to early termination from the study include adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial is conducted in compliance with ethical standards and regulatory requirements, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of Sogroya, a solution for injection containing the active substance somapacitan. Sogroya is available in three different dosages: 5 mg/1.5 mL, 10 mg/1.5 mL, and 15 mg/1.5 mL, all provided in pre-filled pen injectors. The pharmaceutical form is a solution for injection, and the route of administration is subcutaneous. The dosing schedule for Sogroya is once weekly, with a maximum treatment period of 156 weeks. The PDS290 pen-injector, a disposable, pre-filled, multi-dose device, is used for administration. The volume of the dose per increment is dependent on the specific variant of somapacitan PDS290. Participant compliance is monitored through regular assessments and adherence checks. The comparator treatment in this study is Norditropin FlexPro, which contains the active substance somatropin. Norditropin FlexPro is also a solution for injection provided in a pre-filled pen. The route of administration is subcutaneous, and the dosing schedule is once daily. The maximum treatment period for Norditropin FlexPro is 52 weeks. The Norditropin® FlexPro® pen-injector is a disposable, pre-filled, multi-dose device used for administration. Compliance with the daily dosing regimen is monitored through participant logs and regular follow-up visits. Both treatments are manufactured by Novo Nordisk A/S and are not pediatric formulations. The trial aims to confirm the non-inferiority of once-weekly somapacitan compared to once-daily Norditropin in terms of longitudinal growth measured by height velocity at week 52 in children with short stature due to being born small for gestational age, Turner syndrome, Noonan syndrome, or idiopathic short stature. The study design includes regular monitoring of participant adherence to the dosing schedule and assessment of treatment efficacy and safety.

The efficacy of the clinical trial will be assessed primarily through the measurement of height velocity at week 52. This parameter serves as the primary endpoint to confirm the non-inferiority of once-weekly somapacitan compared to once-daily Norditropin® in children with short stature due to being born small for gestational age (SGA), Turner syndrome (TS), Noonan syndrome (NS), or idiopathic short stature (ISS). Secondary endpoints include changes in height standard deviation score (SDS), height velocity SDS, bone age, insulin-like growth factor I (IGF-I) SDS, insulin-like growth factor-binding protein 3 (IGFBP-3) SDS, fasting plasma glucose, homeostatic model assessment-B (HOMA-B), homeostatic model assessment-IR (HOMA-IR), and glycated hemoglobin (HbA1c). These efficacy parameters will be collected and analyzed at specified time points throughout the trial, with the primary endpoint being evaluated at week 52. The trial will utilize validated scales and laboratory tests to ensure the accuracy and reliability of the data collected. The use of the PDS290 pen-injector and Norditropin® FlexPro® pen-injector will facilitate the administration of the investigational products, ensuring consistent dosing and ease of use for participants. The trial is designed to provide comprehensive data on the efficacy of somapacitan in promoting growth in the specified pediatric populations over the course of the study.