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

Phase 3

Active, not recruiting

• Conditions: Genetic Obesity; Obesity
• Interventions: Drug: Setmelanotide; Drug: Placebo

• Registration Number: NCT05093634
• Lead Sponsor: Rhythm Pharmaceuticals, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2021-09-30
• Study First Submitted QC: 2021-10-13
• Study First Posted: 2021-10-26
• Study Start: 2021-12-10
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-01
• Last Update Posted: 2025-07-03
• Primary Completion: 2025-12
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 400

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NCOA1 (SRC1) variant	Setmelanotide	1:1 Randomization
POMC or PCSK1 variant	Placebo	1:1 Randomization
LEPR variant	Setmelanotide	1:1 Randomization
POMC or PCSK1 variant	Setmelanotide	1:1 Randomization
NCOA1 (SRC1) variant	Placebo	1:1 Randomization
SH2B1 variant	Placebo	1:1 Randomization
LEPR variant	Placebo	1:1 Randomization
SH2B1 variant	Setmelanotide	1:1 Randomization

Primary Outcome Measures

Name	Time	Method
Difference in mean change in body weight in patients treated with setmelanotide compared to placebo, assessed as percent change in BMI	Baseline to 52 weeks

Secondary Outcome Measures

Name	Time	Method
The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo	Baseline to 52 weeks
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	Baseline to 52 weeks
The difference in mean percent change in the weekly average most hunger score in patients treated with setmelanotide compared to placebo	Baseline to 52 weeks
The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo	Baseline to 52 weeks

Trial Locations

Locations (56)

Phoenix Children's Hospital; 🇺🇸 Phoenix, Arizona, United States

HonorHealth Bariatric Center; 🇺🇸 Scottsdale, Arizona, United States

Children's Hospital Los Angeles; 🇺🇸 Los Angeles, California, United States

Children's Hospital Colorado; 🇺🇸 Aurora, Colorado, United States

Yale Center for Clinical Investigation; 🇺🇸 New Haven, Connecticut, United States

Advent Health; 🇺🇸 Altamonte Springs, Florida, United States

InQuest Medical Research; 🇺🇸 Suwanee, Georgia, United States

UMASS Memorial Medical Center; 🇺🇸 Worcester, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States

Metro Detroit Endocrinology Center; 🇺🇸 Dearborn, Michigan, United States

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