Efficacy of Semaglutide s.c. Once-weekly on Weight Loss and Management in Adolescents With Monogenic Obesity in Clinical Practice

NCT07302802 | Recruiting FDA Drug

• 1 other identifier: U1111-1307-1203
• Study Type: observational
• Target: 70
• Locations: 5 countries
• Sites: 7

Brief Summary

This observational study aims to assess the effect of once-weekly s.c. semaglutide 2.4 mg as an adjunct to a calorie-reduced diet and increased physical activity on weight loss, change in hunger, body composition, depression, and quality of life after 68 weeks of treatment in adolescents diagnosed with monogenic obesity in routine clinical care.

Conditions

Monogenic Obesity

Keywords

semaglutide; monogenic obesity

Outcome Measures

Primary Outcomes (1)

• Proportion of participants achieving ≥10% BMI reduction from baseline (week 0) to week 68.

  The study evaluates the effect of once-weekly subcutaneous (s.c.) semaglutide 2.4 mg administered as an adjunct to a calorie-reduced diet and increased physical activity in adolescents diagnosed with monogenic obesity. This measure focuses on weight loss effectiveness, with the goal of assessing the impact of the treatment on BMI reduction in a real-world clinical setting after 68 weeks of treatment. The study aims to provide insight into the potential of semaglutide in managing weight in this specific patient population.

  68 weeks

Secondary Outcomes (1)

• Secondary Endpoints for Weight and Health Parameters

  68 weeks

Study Arms (6)

Patients with biallelic variants in the LEPR, PCSK1, POMC, and MC4R gene

Drug: Semaglutide (administered by PDS290 pen-injector)

Patients with monoallelic variants in the LEPR gene

Drug: Semaglutide (administered by PDS290 pen-injector)

Patients with monoallelic variants in the PCSK1 gene

Drug: Semaglutide (administered by PDS290 pen-injector)

Patients with monoallelic variants in the POMC gene

Drug: Semaglutide (administered by PDS290 pen-injector)

Patients with monoallelic variants in the MC4R gene

Drug: Semaglutide (administered by PDS290 pen-injector)

Patients with monoallelic variants in the SH2B1 gene or with 16p11.2 deletions

Drug: Semaglutide (administered by PDS290 pen-injector)

Interventions

Semaglutide (administered by PDS290 pen-injector) DRUG

Treatment with semaglutide as prescribed in routine clinical practice according to summary of product characteristics. The use of semaglutide can be categorised into two groups during enrolment period: 1. new users, or 2. current users (e.g., those continuing semaglutide treatment prescribed in routine clinical practice).

Patients with biallelic variants in the LEPR, PCSK1, POMC, and MC4R gene; Patients with monoallelic variants in the LEPR gene; Patients with monoallelic variants in the MC4R gene; Patients with monoallelic variants in the PCSK1 gene; Patients with monoallelic variants in the POMC gene; Patients with monoallelic variants in the SH2B1 gene or with 16p11.2 deletions

Eligibility Criteria

• Age: 12 Years - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Patients aged ≥12 to \<21 years diagnosed with monogenic obesity, who agreed on treatment with semaglutide, are eligible for study participation.

You may qualify if:

• Treatment with semaglutide as prescribed in routine clinical practice according to summary of product characteristics.
• Informed consent of the patient, their parents, or legally acceptable representative (LAR) of participant and adolescent assent, as age-appropriate.
• Age at time of signing informed consent: ≥12 to \<21 years.
• BMI ≥95th percentile as defined on sex- and age-specific BMI growth charts (CDC.gov)
• Body weight of \>60 kg.
• Diagnosis of monogenic obesity by a Clinical Laboratory Improvement Amendments (CLIA)/ College of American Pathologists (CAP)/International Organisation for Standardization (ISO) 1518-certified laboratory using ACMG criteria as pathogenic (P), likely pathogenic (LP) and variant of uncertain significance (VUS).

You may not qualify if:

• Participation in any interventional clinical trials at the time of enrolment.
• Females of childbearing potential who are not using adequate contraceptive methods (as required by local law or practice)
• Hypersensitivity to the active substance or to any of the excipients listed:
• Disodium phosphate, dihydrate
• Propylene glycol
• Phenol
• Hydrochloric acid (for pH adjustment)
• Sodium hydroxide (for pH adjustment)
• Water for injection
• The safety and efficacy of Wegovy have not been investigated in patients:
• treated with other products for weight management,
• with type 1 diabetes,
• with severe renal impairment (see section 4.2),
• with severe hepatic impairment (see section 4.2),
• with congestive heart failure New York Heart Association (NYHA) class IV. Use in these patients is not recommended

Sponsors & Collaborators

• Prof. Dr. Martin Wabitsch: lead
• Novo Nordisk A/S: collaborator

Study Sites (7)

Assistance Publique-Hôpitaux de Paris (AP-HP), Trousseau Hospital Paris, Pediatric Nutrition Department

Paris, France

NOT YET RECRUITING

Institute for Experimental Pediatric Endocrinology, Charité Universitätsmedizin Berlin

Berlin, 13353, Germany

NOT YET RECRUITING

University Hospital for Children and Adolescents, Center for Pediatric Research, Medical Faculty, University of Leipzig

Leipzig, 04103, Germany

NOT YET RECRUITING

Division of Paediatric Endocrinology and Diabetes, Department of Paediatrics and Adolescent Medicine, Ulm University Medical Centre

Ulm, 89075, Germany

RECRUITING

University Medical Center Rotterdam, Erasmus MC-Sophia Children's Hospital

Rotterdam, 3015 GD, Netherlands

NOT YET RECRUITING

Departments of Pediatrics & Pediatric Endocrinology, Hospital Infantil Universitario Niño Jesús, Universidad Autónoma de Madrid

Madrid, 28009, Spain

NOT YET RECRUITING

Wellcome-MRC Institute of Metabolic Science and NIHR Cambridge Biomedical Research Centre

Cambridge, CB2 0QQ, United Kingdom

NOT YET RECRUITING

Related Publications (5)

• Welling MS, de Groot CJ, Kleinendorst L, van der Voorn B, Burgerhart JS, van der Valk ES, van Haelst MM, van den Akker ELT, van Rossum EFC. Effects of glucagon-like peptide-1 analogue treatment in genetic obesity: A case series. Clin Obes. 2021 Dec;11(6):e12481. doi: 10.1111/cob.12481. Epub 2021 Jul 21.

  PMID: 34291582 BACKGROUND

• Iepsen EW, Have CT, Veedfald S, Madsbad S, Holst JJ, Grarup N, Pedersen O, Brandslund I, Holm JC, Hansen T, Torekov SS. GLP-1 Receptor Agonist Treatment in Morbid Obesity and Type 2 Diabetes Due to Pathogenic Homozygous Melanocortin-4 Receptor Mutation: A Case Report. Cell Rep Med. 2020 Apr 21;1(1):100006. doi: 10.1016/j.xcrm.2020.100006. eCollection 2020 Apr 21.

  PMID: 33205056 BACKGROUND

• Wabitsch M, Farooqi S, Fluck CE, Bratina N, Mallya UG, Stewart M, Garrison J, van den Akker E, Kuhnen P. Natural History of Obesity Due to POMC, PCSK1, and LEPR Deficiency and the Impact of Setmelanotide. J Endocr Soc. 2022 Apr 15;6(6):bvac057. doi: 10.1210/jendso/bvac057. eCollection 2022 Jun 1.

  PMID: 35528826 BACKGROUND

• Courbage S, Poitou C, Le Beyec-Le Bihan J, Karsenty A, Lemale J, Pelloux V, Lacorte JM, Carel JC, Lecomte N, Storey C, De Filippo G, Coupaye M, Oppert JM, Tounian P, Clement K, Dubern B. Implication of Heterozygous Variants in Genes of the Leptin-Melanocortin Pathway in Severe Obesity. J Clin Endocrinol Metab. 2021 Sep 27;106(10):2991-3006. doi: 10.1210/clinem/dgab404.

  PMID: 34097736 BACKGROUND

• Nordang GBN, Busk OL, Tveten K, Hanevik HI, Fell AKM, Hjelmesaeth J, Holla OL, Hertel JK. Next-generation sequencing of the monogenic obesity genes LEP, LEPR, MC4R, PCSK1 and POMC in a Norwegian cohort of patients with morbid obesity and normal weight controls. Mol Genet Metab. 2017 May;121(1):51-56. doi: 10.1016/j.ymgme.2017.03.007. Epub 2017 Mar 29.

  PMID: 28377240 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum, plasma, whole blood (EDTA), fat tissue

MeSH Terms

Interventions

semaglutide

Central Study Contacts

Martin Wabitsch, Prof. Dr.

CONTACT

+4973150057401; martin.wabitsch@uniklinik-ulm.de

Stefanie Zorn, Dr.

CONTACT

+4973150057457; stefanie.zorn@uniklinik-ulm.de

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Target Duration: 68 Weeks
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 10, 2025
• First Posted: December 24, 2025
• Study Start: December 1, 2025
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1); DE (3); GB (1); FR (1); ES (1)