The University of Alberta, in Canada, is recruiting people with Bardet-Biedl syndrome and Alström syndrome for a pivotal Phase 3 trial testing the investigational anti-obesity therapy setmelanotide. The study, run by Rhythm Pharmaceuticals, which is developing the treatment, is expected to begin in late July.
The Canadian part of the worldwide trial, which will be complemented by a genetic study looking to learn more on the genes linked to obesity, will be led by Andrea Haqq, clinical scientist at the Alberta Diabetes Institute (ADI), and a professor in the university’s department of pediatrics.
“One thing that people don’t always recognize about obesity, especially childhood obesity, is that it is very complex. It’s not as simple as eating too much,” Haqq said in a press release. “One of those complex components is the genetic influences on obesity, which actually account for 60 to 70 percent of what sets our body mass index (BMI).”
Most patients with rare obesity disorders — including those with Bardet-Biedl and Alström syndromes — carry variations in one or more genes that disrupt signals important for the melanocortin-4 receptor (MC4R) pathway. This results in severe early-onset obesity and excessive insatiable hunger, called hyperphagia.
Setmelanotide (RM-493) is a potent activator of MC4R signals, and has show signs of promising efficacy in helping patients lose weight and control hunger. Some adult patients have lost nearly 50% of their weight with the treatment, the release says.
“What’s really exciting about this drug is that this is one of the first anti-obesity drugs that doesn’t have the cardiovascular side-effects that previous drugs had,” Haqq said. “As we gain more experience with it, I’m hopeful this trial will make a big splash and lead to other trials for other populations.”
Based on the promising results of earlier Phase 2 trials, Rhythm is running a pivotal Phase 3 study (NCT03746522) to test the safety, and confirm the efficacy, of setmelanotide in reducing body weight and hunger in people with Bardet-Biedl and Alström syndromes. Participants must be ages 6 or older.
In addition to Alberta, Canada, the trial has sites opened in the U.S., in New York and Wisconsin. The first patient was enrolled in January this year.
Participants will first enter a 14-week double blind test in which they are randomly assigned to received once-daily injections under the skin of either setmelanotide or a placebo. This will be followed by a 38-week open-label portion in which all participants will be given setmelanotide.
Treatment will then continue for 14 more weeks. At the end of that period, participants may be enrolled in a separate treatment extension study.
The primary measure of efficacy will be the proportion of participants who lose 10% or more of their body mass after 52 weeks of treatment, compared with their weight as documented at baseline, at the start of the study.
In parallel, Haqq is running a genetic screening on obese children and adults with hyperphagia, hoping to identify new genes involved in obesity. Participants who have other genetic disorders linked to obesity also may be added to the setmelanotide trial in future expansions.
In Canada, the ADI is the study’s primary coordinating center, responsible for recruiting and overseeing other sites across the country as the trial expands.
“We’re fortunate to have very skilled research coordinators with a lot of experience in running these types of trials,” Haqq said. “The ADI also has everything we need in one location so we can do all our work right here, and patients have only one place to come to.”