Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials

Plain-language guide to PMID 33137293 (2020): double-blind and open-label clinical trial, phase iii study of Alpha-MSH and Setmelanotide.

Key Facts

PMID: 33137293
Journal: The lancet. Diabetes & endocrinology
Year: 2020
Study type: Clinical Trial, Phase III
Authors: Clément K et al. (18 authors)
DOI: 10.1016/S2213-8587(20)30364-8

What This Study Did, in Plain Language

What Was Tested

The paper reports a study of Alpha-MSH and Setmelanotide, published as a clinical trial, phase iii.

The melanocortin 4 receptor (MC4R), a component of the leptin-melanocortin pathway, plays a part in bodyweight regulation.

Severe early-onset obesity can be caused by biallelic variants in genes that affect the MC4R pathway.

Who Took Part

The age groups tagged for this paper are children, teenagers, young adults and adults, both men and women.

Participants aged 6 years or older with POMC or LEPR deficiency obesity received open-label setmelanotide for 12 weeks.

How the Study Was Run

The researchers set it up as a double-blind, open-label, placebo-controlled and multicenter study.

As a double-blind Alpha-MSH study, the assignments were hidden from both participants and investigators until the end.

Being open-label, the Alpha-MSH study did not mask who received what.

A placebo (an inactive look-alike) gave the Alpha-MSH group a baseline to be compared against.

More than one site took part, so the participants came from several places.

The methods mention a period of 12 weeks.

These single-arm, open-label, multicentre, phase 3 trials were done in ten hospitals across Canada, the USA, Belgium, France, Germany, the Netherlands, and the UK.

These studies are registered with ClinicalTrials.gov, NCT02896192 and NCT03287960.

What Was Measured

The subject headings attached to it are Adrenal Insufficiency, Anti-Obesity Agents, Obesity, Pro-Opiomelanocortin, Prognosis, Receptor, Melanocortin, Type 4 and Receptors, Leptin.

What This Means in Plain Language

The paper is a double-blind, open-label and placebo-controlled study of Alpha-MSH and Setmelanotide over 12 weeks.

Results are reported in around 7 sentences of the abstract; we leave them to the paper itself rather than summarise them.

The publication is from 2020 (The lancet. Diabetes & endocrinology), a journal based in England.

More context: the Alpha-MSH compound page and the Setmelanotide compound page, all human trials.

Our Notes on the Compounds

Alpha-MSH: A 13-amino-acid hormone that drives skin pigmentation and calms inflammation; afamelanotide (Melanotan I) is an analog.

Setmelanotide: An FDA-approved melanocortin-4 receptor agonist for rare genetic obesity (POMC, PCSK1, LEPR deficiency and Bardet-Biedl syndrome).

Source: PubMed record. This explanation is written by PeptideWhiz from the public record. For research and education only. Not medical advice; no dosing information is given.