DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway
- Registration Number
- NCT04963231
- Lead Sponsor
- Rhythm Pharmaceuticals, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 164
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Stage 1: Setmelanotide (Open-Label) Setmelanotide 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. Stage 2: Setmelanotide (Double-Blind) Setmelanotide 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). Stage 2: Placebo (Double-Blind) Placebo 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).
- Primary Outcome Measures
Name Time Method Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 Baseline to Week 16 BMI was calculated using participant's weight and height assessments, using the following formula: BMI = Kilogram (kg)/ square meter (m\^2).
A significant clinically meaningful response was defined as achieving a ≥5% reduction in BMI from Baseline.
Data are provided for overall and according to participants with specified primary gene. Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
- Secondary Outcome Measures
Name Time Method Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype Baseline, Week 16 BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2 Data are provided for overall and according to participants with specified primary gene.
Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype Baseline, Week 16 BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2 Data are provided for overall and according to participants with specified primary gene.
Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype Baseline, Week 16 BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2 Data are provided for overall and according to participants with specified primary gene.
Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype Baseline, Week 16 Data are provided for overall and according to participants with specified primary gene.
Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype Baseline, Week 16 Data are provided for overall and according to participants with specified primary gene.
Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype Baseline, Week 16 BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. The BMI Z-score indicated the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score indicates a reduction in BMI from Baseline whereas an increase of BMI-Z score indicates an increase in BMI from Baseline.
Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.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 Baseline, Week 16 Daily Hunger Questionnaire for participants ≥12 years of age is self-administered questionnaire and comprises three items. For the assessment of this endpoint, maximal hunger was corresponding to the following question: In the last 24 hours, how hungry did you feel when you were the most hungry? The response was scored separately and averaged on weekly basis. Participants rated their hunger on an 11-point numeric rating scale ranging from 0 to 10 (0 = not hungry at all, and 10 = hungriest possible).
Weekly average at Week 16 was defined as average of the available score values within 7 days in Week 16.
Baseline was defined as the average of the available score values within 7 days before or on the stage 1 open-label treatment.
Results are reported by overall participant results and by specific gene cohort.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 Baseline, Week 16 Daily Hunger Questionnaire for participants ≥12 years of age is self-administered questionnaire and comprises three items. For the assessment of this endpoint, maximal hunger was corresponding to the following question: In the last 24 hours, how hungry did you feel when you were the most hungry? The response was scored separately and averaged on weekly basis. Participants rated their hunger on an 11-point numeric rating scale ranging from 0 to 10 (0 = not hungry at all, and 10 = hungriest possible).
Weekly average at Week 16 was defined as average of the available score values within 7 days in Week 16.
Baseline was defined as the average of the available score values within 7 days before or on the stage 1 open-label treatment.
Results are reported by overall participant results and by specific gene cohort.Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype Baseline, Week 16 BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2.
Data are provided for overall and according to participants with specified primary gene.
Baseline was defined as the last available measurement taken prior to the start of treatment Stage 1 administration.
Trial Locations
- Locations (36)
Ten's Medical Center - Pediatric Endocrinology Clinic
🇺🇸Staten Island, New York, United States
The Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Endocrine Associates of Dallas and Plano
🇺🇸Dallas, Texas, United States
Mississippi Center for Advanced Medicine
🇺🇸Madison, Mississippi, United States
HonorHealth Bariatric Center
🇺🇸Scottsdale, Arizona, United States
Mayo Clinic
🇺🇸Rochester, Minnesota, United States
University of North Carolina
🇺🇸Chapel Hill, North Carolina, United States
University of Patras School of Medicine
🇬🇷Patras, Greece
Chaim Sheba MC, Safra Children's Hospital
🇮🇱Ramat Gan, Israel
InQuest Medical Reseacrh
🇺🇸Suwanee, Georgia, United States
UMass Memorial Medical Center
🇺🇸Worcester, Massachusetts, United States
Mount Sinai
🇺🇸New York, New York, United States
University of Michigan
🇺🇸Ann Arbor, Michigan, United States
Metro Detroit Endocrinology Center
🇺🇸Dearborn, Michigan, United States
Columbia University
🇺🇸New York, New York, United States
Geisinger Clinic
🇺🇸Danville, Pennsylvania, United States
Texas Tech
🇺🇸Amarillo, Texas, United States
Hector Granados PA
🇺🇸El Paso, Texas, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Accurate Clinical Research
🇺🇸Houston, Texas, United States
Rio Grande Valley Endocrine Center
🇺🇸McAllen, Texas, United States
Javara Research
🇺🇸The Woodlands, Texas, United States
Charite - Universitatsmedizin Berlin
🇩🇪Berlin, Germany
Clinical Trials of Texas
🇺🇸San Antonio, Texas, United States
University of Alberta
🇨🇦Edmonton, Alberta, Canada
Universitaetsklinikum Leipzig
🇩🇪Leipzig, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Erasmus Medisch Centrum
🇳🇱Rotterdam, Netherlands
Hospital Infantil Universitario Nino Jesus
🇪🇸Madrid, Spain
Hospital Fundación Jimenez Díaz
🇪🇸Madrid, Spain
Hospital Sant Joan de Deu
🇪🇸Barcelona, Spain
Hospital General de Valencia
🇪🇸Valencia, Spain
University of Cambridge
🇬🇧Cambridge, United Kingdom
Bristol Royal Hospital for Children
🇬🇧Bristol, United Kingdom
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
London Medical - The London Diabetes Centre
🇬🇧London, United Kingdom