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

Obesity Clinical Trial

Official 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05093634
• Other study ID #: RM-493-035
• Status: Recruiting
• Phase: Phase 3
• Start date: December 10, 2021
• Est. completion date: December 2024

Study information

• Verified date: April 2024
• Source: Rhythm Pharmaceuticals, Inc.
• Contact: Rhythm Clinical Trials
• Phone: (857) 264-4280
• Email: clinicaltrials[@]rhythmtx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

Drug:
• Setmelanotide
Subcutaneous Injection
• Placebo
Subcutaneous Injection

Locations

Country	Name	City	State
Canada	University of Alberta - Alberta Diabetes Institute (ADI)	Edmonton	Alberta
France	GH Est Hopital Femme Mere Enfant	Lyon
France	Hu Pitie Salpetriere Aphp	Paris
France	Hopital Armand Trousseau	PARIS Cedex 12
France	Centre Hospitalier Universitaire (CHU) de Bordeaux	Pessac
France	Hôpital Félix Guyon Bellepierre	Saint-Denis
Germany	Charite - Universitatsmedizin Berlin	Berlin
Germany	Endokrinologikum Frankfurt	Frankfurt
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Universitaetsklinikum Ulm	Ulm
Greece	University of Patras School of Medicine	Rio
Israel	Hasharon Hospital	Petah Tikva
Israel	Chaim Sheba MC, Safra Children's Hospital	Ramat Gan
Netherlands	Erasmus Medisch Centrum	Rotterdam
Puerto Rico	University of Puerto Rico	San Juan
Spain	Hospital Sant Joan de Deu, Barcelona	Barcelona
Spain	Hospital Fundación Jimenez Díaz	Madrid
Spain	Hospital Universitario Virgen de la Victoria de Málaga	Málaga
Spain	Hospital General de Valencia	Valencia
United Kingdom	Bristol Royal Hospital for Children	Bristol
United Kingdom	University of Cambridge	Cambridge
United Kingdom	Aintree University Hospital	Liverpool
United Kingdom	London Medical - The London Diabetes Centre	London
United Kingdom	University College London Hospitals NHS Foundation Trust	London
United States	Advent Health	Altamonte Springs	Florida
United States	Texas Tech	Amarillo	Texas
United States	University of Michigan	Ann Arbor	Michigan
United States	Children's Hospital Colorado	Aurora	Colorado
United States	University of Buffalo	Buffalo	New York
United States	St. Luke's Hospital	Chesterfield	Missouri
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Geisinger Clinic	Danville	Pennsylvania
United States	Metro Detroit Endocrinology Center	Dearborn	Michigan
United States	Biopharma Informatic	Houston	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	Children's Hospital Los Angeles	Los Angeles	California
United States	Marshfield Clinic Research Foundation, a Division of Marshfield Clinic, Inc	Marshfield	Wisconsin
United States	Rio Grande Valley Endocrine Center	McAllen	Texas
United States	West Virginia University	Morgantown	West Virginia
United States	Vanderbilt University School of Medicine	Nashville	Tennessee
United States	Yale Center for Clinical Investigation	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Metropolitan Hospital Center	New York	New York
United States	Mount Sinai Hospital	New York	New York
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	UPMC Montefiore	Pittsburgh	Pennsylvania
United States	Endocrine Associates of Dallas and Plano	Plano	Texas
United States	Oregon Health & Science University	Portland	Oregon
United States	Mayo Clinic	Rochester	Minnesota
United States	Washington University in St. Louis	Saint Louis	Missouri
United States	HonorHealth Bariatric Center	Scottsdale	Arizona
United States	Ten's Medical Center - Pediatric Endocrinology Clinic	Staten Island	New York
United States	InQuest Medical Research	Suwanee	Georgia
United States	MultiCare Health System Institute for Research and Innovation	Tacoma	Washington
United States	UMASS Memorial Medical Center	Worcester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
Rhythm Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Greece,  Israel,  Netherlands,  Puerto Rico,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	The proportion of patients who achieve at least 5% reduction in BMI in patients treated with setmelanotide compared to placebo		Baseline to 52 weeks
Secondary	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
Secondary	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
Secondary	The proportion of patients who achieve at least 10% reduction in BMI in patients treated with setmelanotide compared to placebo		Baseline to 52 weeks