RM-493-034: A Study of Setmelanotide In Patients With Specific Gene Defects In The Melanocortin-4 Receptor Pathway (H-50539)

RM-493-034: A 2-Stage (Open-Label Run-In Followed by Randomized Withdrawal), Double-Blind, Placebo-Controlled, Phase 2 Study of Setmelanotide In Patients With Specific Gene Defects In The Melanocortin-4 Receptor Pathway

Introduction:
The melanocortin-4 receptor (MC4R) pathway is the principal regulator of mammalian energy balance and body weight. Originating in the hypothalamus it concertedly modulates appetite (feelings of hunger and satiety), energy intake (as caloric consumption), and energy expenditure (basal metabolism, thermogenesis, and physical activity) to define long-term body weight. In human and animal models, genetic defects in this pathway result in severe forms of early-onset obesity and unrelenting hunger (Farooqi 2008). Mechanistically these forms of obesity arise due to insufficient activation of MC4Rs leading to overconsumption of food and a reduction in energy utilization. 

Purpose: 
To evaluate the proportion of obese patients with genetic defects in the melanocortin-4 receptor (MC4R) pathway who achieve a clinically meaningful reduction in body weight in response to setmelanotide after an initial response to open-label treatment.

Methodology: 
This is a 2-stage (open-label run-in followed by randomized withdrawal), Phase 2 study of obese patients with specific gene defects in the MC4R pathway.

Eligibility: 
Patients between the ages of 6 and 65 years old who have a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity.