SEMAFORCRANIO : Multicenter, Double-blind, Parallel, Randomized Controlled Trial of the Efficacy of Semaglutide in Hypothalamic Obesity Secondary to Craniopharyngioma in Children Aged 12 to 17 Years

NCT07845994 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: 49RC23_03072024-511114-20-00
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 17

Brief Summary

Craniopharyngioma (CP) is a rare embryonic brain tumor of the sellar and parasellar region. Despite its benign histologic characteristics, it is locally aggressive and may cause severe morbidity from invasion into adjacent tissues and structures. Hypothalamic damage due to the tumor or its management is responsible for rapid and massive obesity, one of the most severe sequelae in patients with craniopharyngioma. Current treatment of craniopharyngioma is neurosurgical, possibly completed by radiotherapy. For preventing hypothalamic damage, surgery is the most "sparing" possible for the hypothalamus, possibly completed by a highly conformation radiation treatment, such as proton beam therapy. Despite these therapeutic advances, obesity remains a significant problem in 30 to 50% of cases today. Most studies showed that the mean BMI at diagnosis of childhood craniopharyngioma was 0.5-0.8 ± 1.5 SD score, the mean BMI gain was +2 to +3 ± 2 SD score within 3 years, with a relative stabilization or a slow increase after 3 years. When there is an anterior and posterior hypothalamic involvement (about 50% of the cases), the mean BMI gain is even higher (+4 ± 3 SD score within 3 years). Semaglutide, a GLP1RA in weekly injection, has shown its great effectiveness for losing weight in obese adults and adolescents (mean difference in BMI change - 16.7% with semaglutide vs. placebo after 68 weeks). Preliminary data in obese children with craniopharyngioma have shown a mean 25% difference in annual BMI gain (with semaglutide treatment compared to the previous year with no semaglutide in the same children).

Conditions

Craniopharyngioma, Child

Keywords

Hypothalamic obesity; Pediatric disease; Craniopharyngioma

Outcome Measures

Primary Outcomes (2)

• Change in BMI SD score (according to french references) at 40 weeks

  Co-primary 1 (S40 - RCT): Change in BMI (in SD for age and sex according to French references) after 40 weeks of treatment with semaglutide (dose escalation over 16 weeks followed by a maintenance dose of 2.4 mg/week for 24 weeks) compared to placebo

  40 weeks

• Change in BMI SD score (according to french references) at 80 weeks

  Co-primary 2 (S80 - delayed-start): Change in BMI-SD from baseline to S80: "semaglutide group starting at S0" vs "semaglutide group starting at S40"

  80 weeks

Secondary Outcomes (21)

• Change in BMI in kg/m at 40 weeks compared between semaglutide and placebo

  40 weeks

• Change in BMI in kg/m at 80 weeks between compared between semaglutide and placebo

  80 weeks

• Intra-individual progression of BMI-DS at each visit depending on Semaglutide treatment

  80 weeks

• Effects of 40 weeks of weekly semaglutide treatment on height

  40 weeks

• Effects of 40 weeks of weekly semaglutide treatment on weight

  40 weeks

Study Arms (2)

SEMAGLUTIDE

EXPERIMENTAL

Drug: Semaglutide (Wegovy) weekly injection

PLACEBO

PLACEBO COMPARATOR

Drug: Placebo weekly Injection

Interventions

Semaglutide (Wegovy) weekly injection DRUG

A 40-week randomized, controlled, double-blind semaglutide (versus placebo) intervention (versus placebo), followed by an open phase from weeks 40 to 80 where all participants receive semaglutide. In first 40 weeks period (0-40 weeks), Semaglutide is initiated at a dose of 0.25 mg once weekly for the first 4 weeks, followed by escalation every 4 weeks to 0.50, 1.0, 1.70, and 2.40 mg. In second 40 weeks period (40-80 weeks), Semaglutide is maintened at maximum tolerated dose form 1st period. The recommended target maintenance dose of semaglutide or placebo is 2.4 mg once weekly. Participants are encouraged to reach the recommended semaglutide or placebo target maintenance dose of 2.4 mg once weekly. Those unable to tolerate this dose will be permitted to stay at a lower dose (maximum tolerated dose). At least one attempt to re-escalate to the immediate upper dose is recommended.

SEMAGLUTIDE

Placebo weekly Injection DRUG

A 40-week randomized, placebo double-blind controlled intervention (versus semaglutide injection), followed by an open phase from weeks 40 to 80 where all participants receive semaglutide. In first 40 weeks period (between 0-40 weeks), placebo is initiated in same timing than semaglutide (in other arm). In second 40 weeks period (between 40-80 weeks), Semaglutide is initiated at a dose of 0.25 mg once weekly for the first 4 weeks, followed by escalation every 4 weeks to 0.50, 1.0, 1.70, and 2.40 mg. The recommended target maintenance dose of semaglutide or placebo is 2.4 mg once weekly. Participants are encouraged to reach the recommended semaglutide or placebo target maintenance dose of 2.4 mg once weekly. Those unable to tolerate this dose will be permitted to stay at a lower dose (maximum tolerated dose). At least one attempt to re-escalate to the immediate upper dose is recommended.

PLACEBO

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Age 12 to 17 years
• Treated craniopharyngioma whose last intervention was \>6 months ago and whose tumor is considered stable with :
• surgical treatmentsurgery for the solid area (non-cystic portion) of the tumor was \>6 months ago and whose tumor is considered stable
• irradiation treatment
• Appropriate pituitary replacements (including recombinant growth hormone replacement in case of growth hormone deficiency), as assessed by the attending child's physician, according to international recommendations.
• BMI \> + 2 SD of the French references (overweight and obesity) or BMI gain ≥ + 1 SD over the past 6 to 12 months (in the absence of overweight or obesity)
• Failure to control weight despite strict adherence to dietary guidelines for at least six months (healthy nutrition and physical activity counseling provided by a dietician or other qualified healthcare professional)
• For women patients with spontaneous menarche (without the use of hormone treatment with oestrogens), highly effective contraceptive methods during all study participation (and until 7 weeks after last study drug intake)
• Subjects covered by or having the rights to medical care assurance
• Written consent signed by the parents or legally acceptable representatives of the subject, and child participation agreement

You may not qualify if:

• Other weight loss treatments within 90 days before screening
• Previous surgical treatment for obesity
• Other chronic diseases
• History of pancreatitis (acute or chronic, regardless of the number of years)
• Severe psychiatric disorder (e.g., schizophrenia, bipolar disorder)
• Mental retardation
• A lifetime history of suicidal attempt
• History of NEM2 or medullary thyroid carcinoma, malignant neoplasms/carcinomas in situ, or uncontrolled thyroid disease
• Inability to understand the study
• Major problem of compliance with existing treatments (suggesting that compliance with the protocol will be insufficient)
• Known or suspected abuse of alcohol or recreational drugs
• History of type 1 or type 2 diabetes
• Patient with severe renal insufficiency (eGFR \< 30 mL/min/1,73m2)
• Patient with hepatic impairment (mild to severe)
• Participation in another interventional research modifying management or likely to influence the study's assessment criteria

Sponsors & Collaborators

• University Hospital, Angers: lead

Study Sites (17)

Service Endocrinologie pédiatrique, Angers University Hospital

Angers, France

Location

Endocrinologie Pédiatrique, University hospital of Besançon

Besançon, 25030, France

Location

Service d'endocrinologie, diabétoglogie et obésité pédiatrique, Bordeaux University Hospital

Bordeaux, France

Location

Endocrinologie Pédiatrique, Hôpital Femme Mere Enfants, Lyon University Hospital

Bron, France

Location

Département de Pédiatrie, Dijon University Hospital

Dijon, France

Location

Service de Pédiatrie, Grenoble University Hospital

La Tronche, France

Location

Endocrinologie et diabète de l'enfant, Hopital Bicêtre, Paris University Hospital

Le Kremlin-Bicêtre, France

Location

Endocrinologie, diabète et obésité pédiatrique, Lille University Hospital

Lille, France

Location

Service de pédiatrie multidisciplinaire, Hopital La Timone, Marseille University Hospital

Marseille, France

Location

Service de diabétologie et endocrinologie pédiatriques

Montpellier, France

Location

Unité Endocrinologie et Diabète, Nancy University hospital

Nancy, France

Location

Endocrinologie, diabétologie et Gynécologie pédiatrique, Necker Hospital, Paris University Hospital

Paris, France

Location

Service d'endocrinologie diabétologie pédiatrique, Paris University Hospital

Paris, France

Location

Service de Pédiatrie A, Reims University Hospital

Reims, France

Location

Unité d'Endocrinologie et Diabétologie Pédiatriques, Rennes University Hospital

Rennes, France

Location

Service de Pédiatrie, Strasbourg University Hospital

Strasbourg, France

Location

Unité d'Endocrinologie, Maladies Osseuses et Génétique, Toulouse University Hospital

Toulouse, France

Location

MeSH Terms

Conditions

Craniopharyngioma; Sexual Infantilism

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Hypogonadism

Study Officials

• Régis COUTANT, Professor of Medecine

  University Hospital of Angers

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Regis COUTANT, Professor of Medecine

CONTACT

+ 33 (0)2 41 35 56 55; ReCoutant@chu-angers.fr

Matthieu LE LAY

CONTACT

+33 (0)2 41 35 58 91; DRCI-Promotion-Interne@chu-angers.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 31, 2026
• First Posted: September 29, 2026
• Study Start (Estimated): November 1, 2026
• Primary Completion (Estimated): February 1, 2031
• Study Completion (Estimated): February 1, 2031
• Last Updated: September 29, 2026

Record last verified: 2026-09

Locations

FR (17)