The efficacy and safety of setmelanotide in individuals with Bardet-Biedl syndrome or Alstrom syndrome: Phase 3 trial design

Background: A phase 2 trial has suggested that treatment with the melanocortin-4 receptor (MC4R) agonist setmelanotide is associated with a decrease in hunger and weight-related outcomes in participants with Bardet-Biedl syndrome (BBS) and Alstrom syndrome. Here, we present the study design of an ongoing, randomized, double-blind, placebo-controlled, phase 3 trial to assess the long-term efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS or Alstrom syndrome (ClinicalTrials.gov identifier: NCT03746522). Methods: It was initially planned that similar to 30 participants aged >= 6 years with a clinical diagnosis of BBS or Alstrom syndrome would be enrolled. Participants with obesity as defined by a body mass index >= 30 kg/m(2) (in those aged >= 16 years) or a weight >97th percentile (in those aged 6-15 years) are included. Participants are initially randomized in a 1:1 ratio to receive setmelanotide or placebo for 14 weeks (period 1). Following period 1, all participants receive 38 weeks of open-label treatment with setmelanotide (period 2). In each treatment period, setmelanotide is administered at 3 mg once a day following completion of dose escalation. The primary endpoint is the proportion of participants aged >= 12 years achieving a clinically meaningful reduction from baseline (>= 10%) in body weight after similar to 52 weeks (eg, following period 2). Safety and tolerability are assessed by frequency of adverse events. Conclusions: This pivotal trial is designed to evaluate the efficacy and safety of setmelanotide for the treatment of obesity and hyperphagia in individuals with BBS and Alstrom syndrome. Submission category: Study Design, Statistical Design, Study Protocols.

Automated summary

This is a phase 3 trial investigating the efficacy and safety of the MC4R agonist setmelanotide for treating obesity and hyperphagia in individuals with BBS and Alstrom syndrome. The study aims to enroll 30 participants with the primary endpoint being the proportion of participants achieving a clinically meaningful reduction in body weight after approximately 52 weeks. Safety and tolerability will be assessed by frequency of adverse events.