Real-World Effects of MC4R Agonist Therapy in BBS and Severe Genetic Obesity

NCT07674290 | Recruiting Phase 4

• 1 other identifier: UME-BBS-RWD-001
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Bardet-Biedl syndrome (BBS) and other rare disorders associated with impairment of the melanocortin-4 receptor (MC4R) pathway are characterized by severe early-onset obesity, hyperphagia, and substantial morbidity. Setmelanotide, an MC4R agonist, is approved in Europe for selected genetic obesity disorders and reimbursed in Germany for eligible patients. This study aims to evaluate the effectiveness, safety, treatment persistence, metabolic outcomes, and patient-reported outcomes of Setmelanotide under real-world conditions. The registry is designed to allow future inclusion of additional MC4R agonists as they become approved and clinically available. The study will primarily be conducted at University Hospital Essen and will collect longitudinal routine clinical data from pediatric and adult patients receiving MC4R agonist therapy according to approved indications.

Conditions

Bardet Biedl Syndrome (BBS); Bardet Biedl Syndrome; Bardet-Biedl Syndrome (BBS); Alstrom Syndrome

Keywords

Setmelanotide; Melanocortin-4-receptor; Melanocortin pathway; Bardet-Biedl Syndrome; Hyperphagia; Neurocognitive development; Genetic Obesity

Outcome Measures

Primary Outcomes (3)

• Percent change in BMI z-score

  Relative change in BMI z-Score after initiation of MC4 receptor agonist therapy

  Baseline to 12/24/36/48/60/72 months

• Impact on lipid profile

  Changes in lipid profile measured by cholesterol blood levels

  Baseline to 12/24/36/48/60/72 months

• Change in Hepatic Fat Attenuation

  Hepatic Fat Attenuation will be measured by ultrasound Attenuation imaging across different time points

  Baseline to 12/24/36/48/60/72 months

Secondary Outcomes (5)

• Life quality

  Baseline to 12/24/36/48/60/72 months

• Safety and Tolerability

  Baseline to 12/24/36/48/60/72 months

• Cognitive changes

  Baseline to 12/24/36/48/60/72 months

• Functional brain connectivity

  Baseline to 12/24/36/48/60/72 months

• Changes on hypothalamic-pituitary-gonadal axis

  Baseline to 12/24/36/48/60/72 months

Study Arms (1)

MC4R Therapy

EXPERIMENTAL

Patients receiving approved MC4 receptor agonists according to licensed indications and routine clinical practice.

Drug: Setmelanotide

Interventions

Setmelanotide DRUG

Administration according to approved product labeling and treating physician discretion

MC4R Therapy

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• clinical phenotype corresponding to Bardet-Biedl Syndrome
• genetic testing with notable finding

You may not qualify if:

• patients younger than the age approved for treatment with setmelanotide

Sponsors & Collaborators

• Tom Hühne: lead
• Rhythm Pharmaceuticals, Inc.: collaborator

Study Sites (1)

University Hospital Essen, Deparment of Pediatrics II

Essen, 45147, Germany

RECRUITING

Related Publications (10)

• Collet TH, Dubern B, Mokrosinski J, Connors H, Keogh JM, Mendes de Oliveira E, Henning E, Poitou-Bernert C, Oppert JM, Tounian P, Marchelli F, Alili R, Le Beyec J, Pepin D, Lacorte JM, Gottesdiener A, Bounds R, Sharma S, Folster C, Henderson B, O'Rahilly S, Stoner E, Gottesdiener K, Panaro BL, Cone RD, Clement K, Farooqi IS, Van der Ploeg LHT. Evaluation of a melanocortin-4 receptor (MC4R) agonist (Setmelanotide) in MC4R deficiency. Mol Metab. 2017 Oct;6(10):1321-1329. doi: 10.1016/j.molmet.2017.06.015. Epub 2017 Jul 8.

  PMID: 29031731 BACKGROUND

• Kamermans A, Verhoeven T, van Het Hof B, Koning JJ, Borghuis L, Witte M, van Horssen J, de Vries HE, Rijnsburger M. Setmelanotide, a Novel, Selective Melanocortin Receptor-4 Agonist Exerts Anti-inflammatory Actions in Astrocytes and Promotes an Anti-inflammatory Macrophage Phenotype. Front Immunol. 2019 Oct 4;10:2312. doi: 10.3389/fimmu.2019.02312. eCollection 2019.

  PMID: 31636637 BACKGROUND

• Talbi R, Stincic TL, Ferrari K, Ji Hae C, Walec K, Medve E, Gerutshang A, Leon S, McCarthy EA, Ronnekleiv OK, Kelly MJ, Navarro VM. POMC neurons control fertility through differential signaling of MC4R in kisspeptin neurons. Elife. 2025 Jul 17;13:RP100722. doi: 10.7554/eLife.100722.

  PMID: 40674128 BACKGROUND

• Forsythe E, Haws RM, Argente J, Beales P, Martos-Moreno GA, Dollfus H, Chirila C, Gnanasakthy A, Buckley BC, Mallya UG, Clement K, Haqq AM. Quality of life improvements following one year of setmelanotide in children and adult patients with Bardet-Biedl syndrome: phase 3 trial results. Orphanet J Rare Dis. 2023 Jan 16;18(1):12. doi: 10.1186/s13023-022-02602-4.

  PMID: 36647077 BACKGROUND

• Haqq AM, Chung WK, Dollfus H, Haws RM, Martos-Moreno GA, Poitou C, Yanovski JA, Mittleman RS, Yuan G, Forsythe E, Clement K, Argente J. Efficacy and safety of setmelanotide, a melanocortin-4 receptor agonist, in patients with Bardet-Biedl syndrome and Alstrom syndrome: a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial with an open-label period. Lancet Diabetes Endocrinol. 2022 Dec;10(12):859-868. doi: 10.1016/S2213-8587(22)00277-7. Epub 2022 Nov 7.

  PMID: 36356613 BACKGROUND

• Sweeney P, Gimenez LE, Hernandez CC, Cone RD. Targeting the central melanocortin system for the treatment of metabolic disorders. Nat Rev Endocrinol. 2023 Sep;19(9):507-519. doi: 10.1038/s41574-023-00855-y. Epub 2023 Jun 26.

  PMID: 37365323 BACKGROUND

• Barnett S, Reilly S, Carr L, Ojo I, Beales PL, Charman T. Behavioural phenotype of Bardet-Biedl syndrome. J Med Genet. 2002 Dec;39(12):e76. doi: 10.1136/jmg.39.12.e76. No abstract available.

  PMID: 12471214 BACKGROUND

• Cetiner M, Finkelberg I, Schiepek F, Pape L, Hirtz R, Buscher AK. Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome. Orphanet J Rare Dis. 2024 Nov 12;19(1):425. doi: 10.1186/s13023-024-03400-w.

  PMID: 39533427 BACKGROUND

• Dollfus H, Lilien MR, Maffei P, Verloes A, Muller J, Bacci GM, Cetiner M, van den Akker ELT, Grudzinska Pechhacker M, Testa F, Lacombe D, Stokman MF, Simonelli F, Gouronc A, Gavard A, van Haelst MM, Koenig J, Rossignol S, Bergmann C, Zacchia M, Leroy BP, Mosbah H, Van Eerde AM, Mekahli D, Servais A, Poitou C, Valverde D. Bardet-Biedl syndrome improved diagnosis criteria and management: Inter European Reference Networks consensus statement and recommendations. Eur J Hum Genet. 2024 Nov;32(11):1347-1360. doi: 10.1038/s41431-024-01634-7. Epub 2024 Jul 31.

  PMID: 39085583 BACKGROUND

• Huhne T, Polichronidou IM, Finkelberg I, Brensing P, Jaegers J, Dinkelbach L, Kiewert C, Galetzka W, Huessler EM, Scherer T, Bokenkamp A, Gackler A, Pape L, Cetiner M. Impact of the Melanocortin-4 Receptor Agonist Setmelanotide on MASLD and Kidney Function in Bardet-Biedl Syndrome. J Clin Endocrinol Metab. 2026 Feb 20;111(3):721-733. doi: 10.1210/clinem/dgaf483.

  PMID: 40903014 RESULT

Related Links

• The CoE is dedicated to researching the connections between endocrinology, genetics, neuroscience and metabolism, in particular their regulation via melanocortin receptor signalling pathways in healthy individuals and in common and rare diseases from the

MeSH Terms

Conditions

Bardet-Biedl Syndrome; Alstrom Syndrome; Hyperphagia

Interventions

setmelanotide

Condition Hierarchy (Ancestors)

Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Retinitis Pigmentosa; Eye Diseases, Hereditary; Eye Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Metin Cetiner, PD Dr. med.

  Universitätsmedizin Essen

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tom Hühne, Dr. med.

CONTACT

+49 201 723 86211; tom.huehne@uk-essen.de

Lars Dinkelbach, Dr. med.

CONTACT

lars.dinkelbach@uk-essen.de

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Deputy Director, Medical Coordination in the Center of Excellence Bardet-Biedl Syndrome

Model Details: Prospective real-world observational interventional cohort of patients receiving approved MC4 receptor agonist therapy in routine clinical care.

Study Record Dates

• First Submitted: June 16, 2026
• First Posted: June 29, 2026
• Study Start: January 1, 2023
• Primary Completion (Estimated): December 31, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: June 29, 2026

Record last verified: 2026-06

Locations

DE (1)