EMANATE: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway

What Was Tested

This registered phase 3 trial tested Setmelanotide.

The protocol describes a randomized, double-blind, placebo-controlled trial with independent sub-studies of setmelanotide in patients with obesity and at least one of the specific gene variants in the Melanocortin-4 Receptor pathway: * POMC or PCSK1 (Sub-study 035a) * LEPR (Sub-study 035b) * SRC1 (Sub-study 035c) * SH2B1 (Sub-study 035d) The objectives and endpoints are identical for these sub-studies.

It had four arms (groups): POMC or PCSK1 variant (experimental), LEPR variant (experimental), NCOA1 (SRC1) variant (experimental) and SH2B1 variant (experimental).

1:1 Randomization.

1:1 Randomization.

1:1 Randomization.

The registry classes the interventions as drug.

Who Took Part

The registry lists 296 actual participants took part.

It was open to people of any sex aged from 6 years up to 65 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Patients must have a pre-identified:. Heterozygous genetic variant in the POMC gene or PCSK1 gene. Heterozygous genetic variant in the LEPR gene. Homozygous, heterozygous, or compound heterozygous variant in the NCOA1 (SRC1). Homozygous, heterozygous, or compound heterozygous variant in SH2B1 gene, or chromosomal 16p11.2 deletion encompassing the SH2B1 gene.

The full record lists 12 inclusion and 13 exclusion criteria; among the exclusions: recent history of bariatric surgery; suicidal ideation, attempt or behavior; history or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism.

How the Study Was Run

It was run as a randomized, parallel-group and triple-blind study.

Random assignment meant chance, not the researchers, decided who got Setmelanotide and who got the comparison, which limits bias.

Groups ran in parallel: each of the participants stayed in one arm throughout.

Neither the participants nor the staff measuring them knew who was on Setmelanotide, so expectations could not easily colour the readings.

Those kept unaware of assignments: participant, care provider and investigator.

It started in 2021-12-10 with completion listed for 2025-12-22.

It ran at 56 sites in United States (32), France (5), United Kingdom (5), Germany (4), Spain (4) and Israel (2).

Its stated primary purpose is treatment.

What Was Measured

It also tracked 4 secondary outcomes, for example The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo.

What This Means in Plain Language

Put simply, this is a phase 3, randomized trial of Setmelanotide in 296 people.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Setmelanotide compound page, all human trials.