DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway

NCT ID: NCT04963231

Last Updated: 2025-07-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

164 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-30

Study Completion Date

2024-09-30

Brief Summary

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The purpose of this study was to evaluate the safety and efficacy of once daily subcutaneous (SC) administration of setmelanotide in participants with obesity and specific gene variants in the MC4R pathway.

Detailed Description

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Conditions

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Genetic Obesity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators
Stage 1 of the trial is open-label. Participants who were eligible to enter Stage 2 of the trial were randomized in a blinded manner at the Stage 2 Entry Visit in a 2:1 ratio to receive either setmelanotide or placebo.

Study Groups

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Stage 1: Setmelanotide (Open-Label)

Participants received once daily SC injection of setmelanotide from Day 1 to Week 16 in an open-label treatment stage (Stage 1). Participants ≥12 years of age started on setmelanotide 2.0 milligrams (mg) once daily for approximately 2 weeks, then increased to 3.0 mg once daily. Participants \<12 years of age started on setmelanotide 1.0 mg once daily for approximately 1 week, then increased to 2.0 mg once daily for approximately 1 week, then increased to 3.0 mg once daily.

Group Type EXPERIMENTAL

Setmelanotide

Intervention Type DRUG

SC injection

Stage 2: Setmelanotide (Double-Blind)

Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of setmelanotide 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).

Group Type EXPERIMENTAL

Setmelanotide

Intervention Type DRUG

SC injection

Stage 2: Placebo (Double-Blind)

Participants from Stage 1 who were eligible for Stage 2 received once daily SC injection of matching placebo 3.0 mg from Week 16 to Week 40 in a double-blind treatment Stage (Stage 2).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

SC injection

Interventions

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Setmelanotide

SC injection

Intervention Type DRUG

Placebo

SC injection

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Participants must have had a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity
* Age 6 to 65 years, inclusive
* Obesity, defined as Body Mass Index (BMI) ≥40 kilograms per square meter (kg/m\^2) for participants ≥18 years of age or BMI ≥97th percentile for age and gender for participants 6 to \<18 years of age
* Study participant and/or parent or guardian were able to understand all study procedures and provide consent/assent
* Use of highly effective contraception
* Symptoms or behaviors of hyperphagia

Exclusion Criteria

* Participants with the following genetic variants: biallelic Bardet-Biedl Syndrome (BBS); biallelic Alström Syndrome 1 (ALMS1); homozygous, heterozygous, or compound heterozygous variants in MC4R, Pro-opiomelanocortin (POMC), Proprotein convertase subtilisin/kexin type 1 (PCSK1), Leptin receptor (LEPR), nuclear receptor coactivator 1 (NCOA1; steroid receptor coactivator-1 \[SRC1\]) or SRC homology 2 B adapter protein 1 (SH2B1) genes as well as 16p11.2 chromosomal deletions that included the SH2B1 gene
* Recent intensive diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that had resulted in weight loss \>2% within previous 3 months
* Bariatric surgery within the previous 6 months
* Documented diagnosis of current unstable major psychiatric disorder or a documented worsening of psychiatric condition that required changes in treatment within 2 years
* Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) or Patient Health Questionnaire 9 (PHQ 9) score of ≥15 during Screening, any suicide attempt in participant's lifetime years, or any suicidal behavior in the last month.
* Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study
* Has significant features of (or meets the diagnostic criteria for) a genetic syndrome that is associated with obesity
* Glycated hemoglobin (HbA1C) \>10.0% at Screening
* History of significant liver disease
* Glomerular filtration rate (GFR) \<30 milliliter per minute (mL/min) at Screening
* History or close family history of melanoma or participant history of oculocutaneous albinism
* Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions
* Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing
* Participants previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide
* Significant hypersensitivity to any excipient in the study drug
* Females who were breastfeeding or nursing
Minimum Eligible Age

6 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Rhythm Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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David Meeker, MD

Role: STUDY_CHAIR

Rhythm Pharmaceuticals, Inc.

Locations

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HonorHealth Bariatric Center

Scottsdale, Arizona, United States

Site Status

InQuest Medical Reseacrh

Suwanee, Georgia, United States

Site Status

UMass Memorial Medical Center

Worcester, Massachusetts, United States

Site Status

University of Michigan

Ann Arbor, Michigan, United States

Site Status

Metro Detroit Endocrinology Center

Dearborn, Michigan, United States

Site Status

Mayo Clinic

Rochester, Minnesota, United States

Site Status

Mississippi Center for Advanced Medicine

Madison, Mississippi, United States

Site Status

Mount Sinai

New York, New York, United States

Site Status

Columbia University

New York, New York, United States

Site Status

Ten's Medical Center - Pediatric Endocrinology Clinic

Staten Island, New York, United States

Site Status

University of North Carolina

Chapel Hill, North Carolina, United States

Site Status

Geisinger Clinic

Danville, Pennsylvania, United States

Site Status

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Texas Tech

Amarillo, Texas, United States

Site Status

Endocrine Associates of Dallas and Plano

Dallas, Texas, United States

Site Status

Hector Granados PA

El Paso, Texas, United States

Site Status

Texas Children's Hospital

Houston, Texas, United States

Site Status

Accurate Clinical Research

Houston, Texas, United States

Site Status

Rio Grande Valley Endocrine Center

McAllen, Texas, United States

Site Status

Clinical Trials of Texas

San Antonio, Texas, United States

Site Status

Javara Research

The Woodlands, Texas, United States

Site Status

University of Alberta

Edmonton, Alberta, Canada

Site Status

Charite - Universitatsmedizin Berlin

Berlin, , Germany

Site Status

Universitaetsklinikum Leipzig

Leipzig, , Germany

Site Status

Universitaetsklinikum Ulm

Ulm, , Germany

Site Status

University of Patras School of Medicine

Pátrai, , Greece

Site Status

Chaim Sheba MC, Safra Children's Hospital

Ramat Gan, , Israel

Site Status

Erasmus Medisch Centrum

Rotterdam, , Netherlands

Site Status

Hospital Sant Joan de Deu

Barcelona, , Spain

Site Status

Hospital Infantil Universitario Nino Jesus

Madrid, , Spain

Site Status

Hospital Fundación Jimenez Díaz

Madrid, , Spain

Site Status

Hospital General de Valencia

Valencia, , Spain

Site Status

Bristol Royal Hospital for Children

Bristol, , United Kingdom

Site Status

University of Cambridge

Cambridge, , United Kingdom

Site Status

London Medical - The London Diabetes Centre

London, , United Kingdom

Site Status

University College London Hospitals NHS Foundation Trust

London, , United Kingdom

Site Status

Countries

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United States Canada Germany Greece Israel Netherlands Spain United Kingdom

References

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Trapp CM, Censani M. Setmelanotide: a promising advancement for pediatric patients with rare forms of genetic obesity. Curr Opin Endocrinol Diabetes Obes. 2023 Apr 1;30(2):136-140. doi: 10.1097/MED.0000000000000798. Epub 2023 Feb 1.

Reference Type DERIVED
PMID: 36722447 (View on PubMed)

Cuda S, Censani M. Progress in pediatric obesity: new and advanced therapies. Curr Opin Pediatr. 2022 Aug 1;34(4):407-413. doi: 10.1097/MOP.0000000000001150. Epub 2022 Jul 5.

Reference Type DERIVED
PMID: 35797460 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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RM-493-034

Identifier Type: -

Identifier Source: org_study_id

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