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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire D'Angers

Participant type

Pediatric, Patients

Age range

0-17 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-04-27

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Novo Nordisk · French Ministry of Health

External identifiers

EU CT number

2024-511114-20-00

WHO UTN

U1111-1304-9328

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the efficacy of semaglutide on the change in BMI (in standard deviations for age and sex according to French reference values) in children aged 12–17 years with hypothalamic obesity secondary to craniopharyngioma, using two randomized confirmatory comparisons: (i) at 40 weeks (semaglutide vs. placebo) and (ii) at 80 weeks (early initiation vs. delayed initiation).

Secondary objectives 4

1. To evaluate the effects of weekly semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks depending on treatment tolerance) compared to a placebo in children aged 12-17 years with rapid weight gain or overweight/obesity secondary to craniopharyngioma, despite lifestyle intervention in terms of 1) clinical parameters (waist circumference, height, weight, blood pressure), 2) biological parameters (blood glucose, insulin, HbA1c, lipid profile, pituitary hormones), 3) body composition (by DXA), 4) eating behavior and quality of life (by questionnaires), 5) safety (significant adverse events, tumor recurrence or evolution by cranial MRI, liver enzymes, pancreatic enzymes, calcitonin, …).
2. To evaluate efficiency and safety of semaglutide during 40 weeks unblinded extension phase for all children.
3. To evaluate the kinetics of weight evolution of semaglutide treated patients.
4. To describe the intra-individual trajectory of BMI-DS over time and to explore the association between cumulative semaglutide exposure and BMI-DS

Conditions and MedDRA coding

Craniopharyngioma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Age 12 to 17 years
2. Surgically treated craniopharyngioma whose last surgery for the solid area (non-cystic portion) of the tumor was >6 months ago and whose tumor is considered stable
3. 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
4. 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)
5. Failure to control weight despite strict adherence to dietary guidelines for at least six months (consisting of healthy nutrition and physical activity counseling provided by a dietician or other qualified healthcare professional)
6. 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 the last dosing of study drug)
7. Subjects covered by or having the rights to medical care assurance
8. Written consent signed by the parents or legally acceptable representatives of the subject, and child participation agreement

Exclusion criteria 16

1. Other weight loss treatments within 90 days before screening
2. Major problem of compliance with existing treatments (suggesting that compliance with the protocol will be insufficient)
3. Any disorder, unwillingness, or inability, not covered by any of the other exclusion criteria which, in the investigator’s opinion, might jeopardize the participant’s safety or compliance with the protocol
4. Known or suspected abuse of alcohol or recreational drugs
5. History of type 1 and type 2 diabetes
6. Participation in another interventional research modifying management or likely to influence the study's assessment criteria
7. Pregnancy or desire of pregnancy, breast-feeding patients and parturients
8. Previous surgical treatment for obesity
9. Other chronic diseases
10. History of pancreatitis (acute or chronic, regardless of the number of years)
11. Severe psychiatric disorder (e.g., schizophrenia, bipolar disorder)
12. Mental retardation
13. A lifetime history of suicidal attempt
14. History of NEM2 or medullary thyroid carcinoma, malignant neoplasms/carcinomas in situ, or uncontrolled thyroid disease
15. Inability to understand the study
16. Calcitonin ≥ 50 ng/L

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Change in BMI (in standard deviations for age and sex according to French reference values) after 40 weeks of semaglutide treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week for 24 weeks) compared to placebo. treatment (dose escalation over 16 weeks followed by a maximum maintenance dose of 2.4 mg/week during 24 weeks) versus placebo
2. Evolution of BMI-DS between baseline and S80: “semaglutide from S0” arm vs “semaglutide from S40” arm.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire D'Angers

Sponsor organisation

Centre Hospitalier Universitaire D'Angers

Address

4 Rue Larrey

City

Angers

Postcode

49100

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire D'Angers

Contact name

Coordinating investigator

Public contact point

Organisation

Centre Hospitalier Universitaire D'Angers

Contact name

Promotion interne CHU

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications