Phase 2
N=164
DAYBREAK: A Study of Setmelanotide in Participants With Specific Gene Variants in the Melanocortin-4 Receptor (MC4R) Pathway
Genetic Obesity
Bottom Line
View on ClinicalTrials.gov: NCT04963231 ↗Enrolled (actual)
164
Serious AEs
2.8%
Results posted
Oct 2024
Primary outcome: Primary: Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 — 49; 0; 0; 2 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Setmelanotide (Drug); Placebo (Drug)
- Age
- Pediatric, Adult, Older Adult · 6+ yrs
- Sex
- All
- Sponsor
- Rhythm Pharmaceuticals, Inc.
- Primary completion
- Aug 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1 |
49; 0; 0; 2; 3; 2 | — |
| SECONDARY Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype |
45.338; -1.916; 48.601; 0.229; 46.568; -1.040 | — |
| SECONDARY Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype |
48.464; -1.872; 51.640; -0.783; 46.959; -0.678 | — |
| SECONDARY Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype |
-4.62; 0.57; -4.00; -2.33; -4.90; -8.95 | — |
| SECONDARY Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype |
-3.95; -1.37; -1.22; -4.69; -9.06; -5.34 | — |
| SECONDARY Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype |
136.01; -5.33; 147.35; -2.03; 145.30; -2.33 | — |
| SECONDARY Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype |
-3.94; -1.37; -1.22; -4.69; -9.06; -5.34 | — |
| SECONDARY Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype |
2.649; -0.126; 2.919; -0.000; 2.386; -0.086 | — |
| SECONDARY 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 |
-31.13; -39.63; -21.04; -44.12; -49.25; -54.61 | — |
| SECONDARY 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 |
49; 2; 1; 3; 2; 6 | — |
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 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.
Data sourced from ClinicalTrials.gov (NCT04963231). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.