A study evaluating the safety and efficacy of once-weekly dosing of somapacitan in a basket study design in paediatric participants with short stature either born small of gestational age or with Turner syndrome, Noonan syndrome or idiopathic short stature

The primary objective of this study is to evaluate the **safety** of once-weekly somapacitan in pediatric patients, either naïve or non-naïve to growth hormone (GH) treatment, across four specific indications: small for gestational age (SGA), Turner syndrome (TS), Noonan syndrome (NS), and idiopathic short stature (ISS). This is clinically relevant as it aims to ensure the safe administration of somapacitan, a growth hormone therapy, in children with these conditions, potentially improving their growth outcomes and quality of life.

Secondary objectives include:

• Evaluating the long-term safety of once-weekly somapacitan in the same pediatric population, which is crucial for understanding the extended impact of the treatment.
• Assessing the efficacy of somapacitan, which will provide insights into its effectiveness in promoting growth in children with the specified conditions.
• Investigating the steady state pharmacokinetics of somapacitan, which will help in understanding the drug's behavior in the body over time, ensuring optimal dosing and therapeutic outcomes.

The clinical trial involves a total of **24 participants** who are children diagnosed with one of the following conditions: **Small for gestational age**, **Idiopathic short stature**, **Noonan syndrome**, or **Turner’s syndrome**. The study population includes both male and female subjects, indicating a diverse gender representation. Participants are children, with specific age ranges not disclosed in the provided data. The trial population was selected based on their diagnosis and the presence of open epiphyses, as defined by bone age criteria. The study includes children who are either naïve or non-naïve to growth hormone treatment. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The selection criteria ensure that the participants are a vulnerable population, which is a significant aspect of the study. The sponsor has not provided detailed information on the general health status or specific age ranges of the participants.

The clinical trial is designed to evaluate the safety and efficacy of **somapacitan**, a **solution for injection**, administered once weekly in pediatric participants with conditions such as small for gestational age, idiopathic short stature, Noonan syndrome, and Turner's syndrome. This study employs a randomized, double-blind, controlled trial design to ensure the reliability and validity of the results. The trial is expected to span from February 2023 to March 2027, with participant involvement lasting up to 156 weeks. The primary objective is to assess the number of adverse events from week 0 to week 26, while secondary endpoints include changes in height velocity and other growth-related parameters over the same period.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on specific criteria, such as age and diagnosis according to local clinical practice. Following the screening, participants will attend regular follow-up visits to monitor safety and efficacy outcomes, including the measurement of height and other growth indicators. The end-of-study visit will conclude the participant's involvement, where final assessments will be conducted to evaluate the long-term effects of the treatment.

The expected length of participant involvement is approximately 3 years, with conditions for early termination including the occurrence of significant adverse events or withdrawal of consent. The study will utilize a prefilled, fixed, multi-dose pen-injector for subcutaneous administration of somapacitan, ensuring consistent dosing throughout the trial. The trial's design and procedures are structured to maintain the highest standards of scientific rigor and ethical conduct, providing valuable insights into the treatment of growth-related conditions in children.

The clinical trial involves the administration of **Somapacitan**, a **solution for injection** developed by Novo Nordisk A/S. The investigational product, Somapacitan 15 mg/1.5 ml PDS290, is designed for subcutaneous administration. The active substance, somapacitan, is a protein-based compound. The dosing regimen for this trial is once-weekly, with a maximum daily dose of 0.24 mg/kg and a total maximum dose of 37.44 mg/kg over a treatment period of up to 247 days. The solution is delivered using a prefilled, fixed, multi-dose pen-injector, which is intended for single-patient use. This device facilitates the subcutaneous injection of the somapacitan solution.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The trial aims to evaluate the safety and efficacy of somapacitan in pediatric participants with short stature conditions, including those born small for gestational age, or with Turner syndrome, Noonan syndrome, or idiopathic short stature. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

The efficacy of the clinical trial evaluating once-weekly dosing of **somapacitan** in pediatric participants with short stature will be assessed using several primary and secondary endpoints. The primary endpoint is the number of adverse events (AEs) recorded from week 0 to week 26. Secondary endpoints include the number of AEs possibly or probably related to somapacitan from week 0 to week 26, the number of AEs from week 0 to week 156, and various growth-related measures. These growth measures include Height Velocity, Change in Height SDS, Change in Height Velocity SDS, Change in IGF-1 SDS, and Change in IGFBP-3 SDS, all evaluated from week 0 to week 26. Additionally, the weekly average somapacitan concentration (C[avg]) will be determined based on population pharmacokinetic analysis from week 0 to week 26.