Efficacy of Semaglutide in Children Aged 12–17 Years with Hypothalamic Obesity Secondary to Craniopharyngioma: A Randomized Controlled Trial

The primary objective is to evaluate the efficacy of semaglutide on the change in body mass index (BMI) expressed in standard deviations for age and sex in children aged 12 to 17 years with hypothalamic obesity secondary to craniopharyngioma. This is assessed through two randomized comparisons: a comparison of semaglutide versus placebo at 40 weeks, and a comparison of early versus delayed initiation at 80 weeks. 5

Secondary objectives include the evaluation of the following parameters in children with rapid weight gain or overweight/obesity secondary to craniopharyngioma:

• Clinical parameters, including waist circumference, height, weight, and blood pressure;
• Biological parameters, such as blood glucose, insulin, HbA1c, lipid profile, and pituitary hormones;
• Body composition assessed via dual-energy X-ray absorptiometry (DXA);
• Eating behavior and quality of life;
• Safety markers, including significant adverse events, tumor recurrence or evolution via magnetic resonance imaging (MRI), liver enzymes, pancreatic enzymes, and calcitonin.

The sponsor did not provide information regarding the total number of participants. The study population consists of male and female patients aged 12 to 17 years diagnosed with hypothalamic obesity secondary to craniopharyngioma. Eligible participants include those with a surgically treated, stable tumor where the last surgery for the solid component occurred more than six months prior. Inclusion requires appropriate pituitary replacement therapy and a body mass index exceeding +2 standard deviations of French reference values, or a gain of at least +1 standard deviation over the previous 6 to 12 months. Participants must have demonstrated a failure to control weight despite at least six months of strict adherence to dietary guidelines and physical activity counseling. For females with spontaneous menarche not receiving estrogen treatment, the use of highly effective contraception is required throughout the study and until seven weeks following the final dose.

This multicenter, double-blind, parallel, randomized controlled trial evaluates the efficacy of semaglutide in treating hypothalamic obesity secondary to craniopharyngioma in patients aged 12 to 17 years. The study compares a 2.4 mg subcutaneous injection of semaglutide against a placebo. The research methodology involves two randomized confirmatory comparisons to assess changes in body mass index (BMI) expressed in standard deviations. The first comparison occurs at 40 weeks, involving a 16-week dose escalation followed by a 24-week maintenance period. The second comparison occurs at 80 weeks to evaluate early versus delayed initiation of treatment. Participants must have a stable, surgically treated tumor and meet specific BMI criteria. The total duration of participant involvement is determined by the treatment arm and the specific comparison endpoint being measured.

The experimental treatment consists of semaglutide, provided as a solution for injection in a pre-filled pen. The administered dose is 2.4 mg via subcutaneous injection.

The control group receives a placebo, administered as a Wegovy 2.4 mg solution for injection in a pre-filled pen.

The primary efficacy assessment is the change in body mass index (BMI), expressed in standard deviations for age and sex according to French reference values, following 40 weeks of treatment. The treatment regimen consists of a 16-week dose escalation followed by a 24-week maintenance period at a dose of 2.4 mg per week of semaglutide, compared to a placebo.

A second primary endpoint evaluates the evolution of BMI-DS between baseline and week 80. This comparison is conducted between the arm receiving semaglutide from the start of the study and the arm receiving semaglutide starting at week 40.