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NCT Number: NCT05093634

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

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.

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Key information

Conditions

Obesity Body Weight Genetic Obesity Hyperphagia Nutrition Disorders Nutritional and Metabolic Diseases Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms Signs and Symptoms, Digestive

Age range

6 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

University of Alberta - Alberta Diabetes Institute (ADI), Edmonton, Alberta, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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
  • Between 6 and 65 years of age at the time of provision of informed consent/assent
  • Obesity, defined as BMI ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and gender for patients 6 up to 17 years of age
  • Patient and/or parent or guardian is able to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent
  • Patient and/or parent or guardian reports that patient experienced childhood obesity, defined as the patient and/or parent or guardian reporting that the patient was significantly overweight during childhood
  • Agree to use a highly effective form of contraception throughout the study and for 90 days following the study
  • Reported history of lifestyle intervention of diet and exercise
  • Reported history of hyperphagia

Key Exclusion Criteria:

  • Weight loss of 2% or greater in the previous 3 months
  • Recent history of bariatric surgery
  • Significant psychiatric disorder(s)
  • Suicidal ideation, attempt or behavior
  • Clinically significant pulmonary, cardiac, endocrine/metabolic, hepatic or oncologic disease
  • Glycated hemoglobin (HbA1C) >10% at Screening
  • History of significant liver disease or severe kidney disease
  • History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism
  • Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
  • Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing
  • Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide
  • Significant hypersensitivity to any excipient in the study drug
  • If female, pregnant or breastfeeding

Treatment and study plan

Setmelanotide

Drug

Subcutaneous Injection

Placebo

Drug

Subcutaneous Injection

Primary outcomes

  1. Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI

    Time frame: Baseline to 52 weeks

Secondary outcomes

  1. The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo

    Time frame: Baseline to 52 weeks

  2. The difference in mean change in body weight in adult patients treated with setmelanotide compared to placebo, assessed as percent change in baseline body weight

    Time frame: Baseline to 52 weeks

  3. The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo

    Time frame: Baseline to 52 weeks

  4. The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo

    Time frame: Baseline to 52 weeks

Sponsors and collaborators

Lead sponsor

Rhythm Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Trial: Multiple Independent Sub-studies of Setmelanotide in Patients With POMC/PCSK1, LEPR, NCOA1(SRC1), or SH2B1 Gene Variants in the Melanocortin-4 Receptor Pathway

Important dates

Study start
2021
Primary completion
2025
Study completion
2026
First posted
Oct 26, 2021
Registry last updated
Feb 10, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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