Clinical trial NCT04963231: DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway
Official title: A 2-Stage (Open-Label Followed by Randomized Double-Blind, Placebo-Controlled Stage), Phase 2 Trial of Setmelanotide in Patients With Specific Gene Variants in the Melanocortin-4 Receptor Pathway
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Genetic Obesity
Keywords: Melanocortin-4 Receptor
Genetic Obesity
Leptin
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2021-07-15
Enrollment: 164
Sex: ALL
Minimum age (years): 6
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Key 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

Key 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

Other protocol defined Inclusion/Exclusion criteria applied.

Primary outcomes:
measure: Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1
timeFrame: Baseline to Week 16
Secondary outcomes:
measure: Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype
timeFrame: Baseline, Week 16
measure: Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype
timeFrame: Baseline, Week 16
measure: Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype
timeFrame: Baseline, Week 16
measure: Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype
timeFrame: Baseline, Week 16
measure: Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype
timeFrame: Baseline, Week 16
measure: Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype
timeFrame: Baseline, Week 16
measure: Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype
timeFrame: Baseline, Week 16
measure: Percent Change in the Weekly Average of the Daily Maximal Hunger Score From Baseline to the End of Stage 1 in Participants ≥12 Years Old, Per Genotype
timeFrame: Baseline, Week 16
measure: Number of Participants ≥12 Years Old, Who Achieved a ≥2 Point Reduction From Baseline to the End of Stage 1 in the Weekly Average of the Daily Maximal Hunger Score, Per Genotype
timeFrame: Baseline, Week 16
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: HonorHealth Bariatric Center
state: Arizona
city: Suwanee
country: United States
facility: InQuest Medical Reseacrh
state: Georgia
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Dearborn
country: United States
facility: Metro Detroit Endocrinology Center
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Madison
country: United States
facility: Mississippi Center for Advanced Medicine
state: Mississippi
city: New York
country: United States
facility: Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University
state: New York
city: Staten Island
country: United States
facility: Ten's Medical Center - Pediatric Endocrinology Clinic
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Danville
country: United States
facility: Geisinger Clinic
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Children's Hospital of Philadelphia
state: Pennsylvania
city: Amarillo
country: United States
facility: Texas Tech
state: Texas
city: Dallas
country: United States
facility: Endocrine Associates of Dallas and Plano
state: Texas
city: El Paso
country: United States
facility: Hector Granados PA
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research
state: Texas
city: McAllen
country: United States
facility: Rio Grande Valley Endocrine Center
state: Texas
city: San Antonio
country: United States
facility: Clinical Trials of Texas
state: Texas
city: The Woodlands
country: United States
facility: Javara Research
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Patras
country: Greece
facility: University of Patras School of Medicine
city: Ramat Gan
country: Israel
facility: Chaim Sheba MC, Safra Children's Hospital
city: Rotterdam
country: Netherlands
facility: Erasmus Medisch Centrum
city: Barcelona
country: Spain
facility: Hospital Sant Joan de Deu
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus
city: Madrid
country: Spain
facility: Hospital Fundación Jimenez Díaz
city: Valencia
country: Spain
facility: Hospital General de Valencia
city: Bristol
country: United Kingdom
facility: Bristol Royal Hospital for Children
city: Cambridge
country: United Kingdom
facility: University of Cambridge
city: London
country: United Kingdom
facility: London Medical - The London Diabetes Centre
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
Study officials:
affiliation: Rhythm Pharmaceuticals, Inc.
name: David Meeker, MD
role: STUDY_CHAIR
References:
citation: 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.