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

Robert M Haws, Gregory Gordon, Joan C Han, Jack A Yanovski, Guojun Yuan, Murray W Stewart, Robert M Haws, Gregory Gordon, Joan C Han, Jack A Yanovski, Guojun Yuan, Murray W Stewart

Abstract

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 Alström 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 Alström syndrome (ClinicalTrials.gov identifier: NCT03746522).

Methods: It was initially planned that ~30 participants aged ≥6 years with a clinical diagnosis of BBS or Alström syndrome would be enrolled. Participants with obesity as defined by a body mass index ≥30 kg/m2 (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 ~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 Alström syndrome.

Submission category: Study Design, Statistical Design, Study Protocols.

Keywords: Antiobesity drug; Appetite control; Obesity therapy; Phase III study.

Conflict of interest statement

RMH is a consultant for Rhythm Pharmaceuticals, Inc and Trinity Life Sciences and receives grant funding from the Bardet-Biedl Syndrome Foundation. GG, GY, and MWS are employed by and may own stock in Rhythm Pharmaceuticals, Inc. JCH has received grant support for clinical investigations from the Memphis Research Consortium, Le Bonheur Children's Foundation Research Institute, and Rhythm Pharmaceuticals, Inc. JAY receives grant support for clinical investigations from the NICHD, NIH, Soleno Therapeutics Inc, and Rhythm Pharmaceuticals, Inc.

© 2021 The Authors. Published by Elsevier Inc.

Figures

Fig. 1
Fig. 1
Schematic for the design of the overall study. Escal., escalation; QD, once a day; SET, setmelanotide. aDuring dose escalation, participants who are ≥16 years of age receive setmelanotide 2 mg QD for 2 weeks, which increases to 3 mg at the beginning of week 3; participants who are <16 years of age receive setmelanotide 1 mg QD for the first week, 2 mg for the second week, and 3 mg at the beginning of week 3.

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