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

Официальное название

Real-World Effectiveness, Safety and Patient-reported Outcomes of Setmelanotide in Patients With Bardet-Biedl Syndrome: A Prospective Mono Centric Observational Interventional Study

Обзор

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.

Подробное описание

The MC4R signaling pathway is a key regulator of appetite and energy balance. Genetic defects affecting this pathway lead to severe obesity syndromes including Bardet-Biedl syndrome and other rare monogenic obesity disorders. Although pivotal clinical trials demonstrated efficacy of Setmelanotide, evidence from routine clinical care remains limited. This study seeks to characterize treatment outcomes in everyday clinical practice, including changes in body weight, BMI, hyperphagia, metabolic parameters, quality of life, treatment adherence, and adverse events. Patients receiving approved MC4R agonist therapy will be followed prospectively. Data will be collected during routine outpatient visits and include anthropometric, clinical, laboratory, and patient-reported measures. The study infrastructure is intended to serve as a platform for future MC4R agonists approved for severe genetic obesity disorders.

Вмешательства

• Препарат Setmelanotide
  Administration according to approved product labeling and treating physician discretion

Первичные конечные точки

• Percent change in BMI z-score [Срок оценки: Baseline to 12/24/36/48/60/72 months]
• Impact on lipid profile [Срок оценки: Baseline to 12/24/36/48/60/72 months]
• Change in Hepatic Fat Attenuation [Срок оценки: Baseline to 12/24/36/48/60/72 months]

Вторичные конечные точки (5)

• Life quality [Срок оценки: Baseline to 12/24/36/48/60/72 months]
• Safety and Tolerability [Срок оценки: Baseline to 12/24/36/48/60/72 months]
• Cognitive changes [Срок оценки: Baseline to 12/24/36/48/60/72 months]
• Functional brain connectivity [Срок оценки: Baseline to 12/24/36/48/60/72 months]
• Changes on hypothalamic-pituitary-gonadal axis [Срок оценки: Baseline to 12/24/36/48/60/72 months]

Критерии участия

Критерии включения

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

Критерии исключения

• patients younger than the age approved for treatment with setmelanotide

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Германия · 1 центр

• University Hospital Essen, Deparment of Pediatrics II — Essen

Публикации

• 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 PMID 29031731
• 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
• 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
• 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
• 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. PMID 36356613
• 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
• 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
• 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

Идентификаторы

NCT: NCT07674290 · UME-BBS-RWD-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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