Evaluation of Semaglutide and Low Energy Diet in Adolescents with Obesity: A Randomized Controlled Trial

The primary objective of the study is to confirm the **superiority** of once-weekly semaglutide subcutaneous (s.c.) 2.4 mg compared to a placebo, both administered as an adjunct to a 52-week blended face-to-face and electronic behavioral therapy (eBT) program. This is targeted at treatment-seeking adolescents aged 12 to less than 18 years with **obesity**, focusing on the percentage reduction in body weight (% BMI change) following the completion of an initial 8-week blended face-to-face and electronic low energy diet (eLED). The clinical relevance of this objective lies in its potential to provide an effective treatment strategy for adolescent obesity, a condition associated with significant health risks and long-term complications.

The secondary objectives include:

• Comparing the safety and tolerability of semaglutide s.c. 2.4 mg once-weekly versus placebo as an adjunct to eBT from week 8 to 60.
• Evaluating the effect of semaglutide on various measures such as body composition, cardiometabolic risk factors, biomarkers, physical activity, sleep, and patient-reported outcomes.
• Assessing the feasibility, safety, and preliminary effectiveness of an 8-week eLED intervention from week 0 to 7.
• Evaluating the feasibility of a 52-week eBT intervention for weight loss maintenance from week 8 to 60.

The clinical trial involves a study population of **adolescents** aged 12 to less than 18 years, comprising both male and female participants. The trial focuses on individuals with **obesity**, specifically those with a Body Mass Index (BMI) of 35 kg/m² or higher, or a BMI of 30 kg/m² with at least one weight-related comorbidity, risk factor, or complication. Participants are required to have a history of at least one self-reported unsuccessful dietary effort to lose body weight. The trial population was selected based on their treatment-seeking status and the ability to provide informed consent, with the consent of a parent or legally authorized representative. The sponsor has not provided information regarding the total number of participants. The study includes a vulnerable population, emphasizing the need for careful ethical considerations. Participants are engaged in a 52-week blended face-to-face and electronic behavioral therapy program, which is an adjunct to the trial's primary intervention. Lifestyle considerations such as diet and physical activity are integral to the study, given the focus on weight management and behavioral therapy.

The clinical trial is designed to evaluate the efficacy of **semaglutide** in treating adolescents with **obesity**. This is a randomized, double-blind, controlled trial comparing once-weekly subcutaneous injections of semaglutide 2.4 mg with a placebo, both as adjuncts to a 52-week blended face-to-face and electronic behavioral therapy program. The primary objective is to assess the percentage reduction in body weight, specifically the change in BMI, from week 8 to week 60. Secondary endpoints include the evaluation of adverse events, physical activity, sleep, psychiatric symptoms, eating disorder symptoms, health-related quality of life, and changes in fat mass, fat-free mass, blood glucose, blood lipids, blood pressure, and other cardiometabolic risk factors.

The trial is expected to commence recruitment on January 1, 2024, and conclude by March 1, 2027. Participants will be involved in the study for approximately 60 weeks. The study visits are structured as follows: an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor progress and collect data on the primary and secondary endpoints. The end-of-study visit will occur at the conclusion of the 60-week period to finalize data collection and assess the overall outcomes of the intervention.

Inclusion criteria require participants to be adolescents aged 12 to less than 18 years, with a BMI of at least 35 kg/m² or a BMI of at least 30 kg/m² with one weight-related comorbidity. Participants must have a history of at least one unsuccessful dietary effort to lose weight and be capable of providing informed consent. Conditions that may lead to early termination from the study include non-compliance with the study protocol, withdrawal of consent, or the occurrence of significant adverse events. The trial is categorized as a Phase 4 trial, indicating it is conducted post-marketing to gather additional information on the drug's effect in a larger population.

The clinical trial involves the administration of **semaglutide**, a **solution for injection** with a concentration of 3.0 mg/mL, identified as PDS290. The active substance, semaglutide, is a protein of other origin. The trial protocol specifies a maximum daily dose of 0.34 mg and a total maximum dose of 2.4 mg over a treatment period of 12 weeks. The administration route is subcutaneous injection, with a frequency of once weekly. The semaglutide solution is intended to be used as an adjunct to a 52-week blended face-to-face and electronic behavioral therapy program for adolescents aged 12 to less than 18 years with obesity. The primary objective is to assess the percentage reduction in body weight, specifically the change in body mass index (BMI).

The study also includes a **placebo** group, which receives a semaglutide placebo solution for injection. The placebo is administered in the same manner as the active treatment, with a once-weekly subcutaneous injection. This comparator is used to evaluate the efficacy of semaglutide by providing a control for the behavioral therapy program. The placebo is designed to be indistinguishable from the active treatment to ensure blinding of participants and investigators. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Efficacy in the clinical trial titled "eHealth Based treatment of AdolescenT obesiTy with Low energy diet and sEmaglutide (eBATTLE Obesity)" will be assessed primarily through the **percentage change in BMI** from week 8 to week 60. This primary endpoint will evaluate the effectiveness of once-weekly subcutaneous semaglutide 2.4 mg compared to a placebo, both administered as part of a 52-week blended face-to-face and electronic behavioral therapy program in adolescents with obesity.

Secondary endpoints will include a comprehensive assessment of various health parameters. These will encompass the number and severity of adverse events, physical activity levels, sleep patterns, psychiatric symptoms, eating disorder symptoms, and health-related quality of life. Additionally, changes in fat mass, fat-free mass, blood glucose, blood lipids, blood pressure, and other cardiometabolic risk factors will be analyzed to compare the treatment groups. The collection and analysis of these parameters will provide a detailed understanding of the treatment's impact on the participants' overall health and well-being.