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Completed

NCT Number: NCT04963231

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

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.

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Key information

Conditions

Genetic Obesity

Age range

6 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

University of Alberta, Edmonton, Alberta, Canada

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Setmelanotide

Drug

SC injection

Placebo

Drug

SC injection

Primary outcomes

  1. Stage 1: Number of Participants by Genotype Who Demonstrated a Significant Clinically Meaningful Response to Setmelanotide at the End of Stage 1

    Time frame: 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 outcomes

  1. Mean Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype

    Time frame: 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.

  2. Mean Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype

    Time frame: 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.

  3. Percent Change in BMI From Baseline to the End of Stage 1 in All Participants, Per Genotype

    Time frame: 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.

  4. Percent Change in BMI From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype

    Time frame: 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.

  5. Mean Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype

    Time frame: 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.

  6. Percent Change in Body Weight From Baseline to the End of Stage 1 in Participants ≥18 Years Old, Per Genotype

    Time frame: 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.

  7. Mean Change in BMI Z-score From Baseline to the End of Stage 1 in Participants <18 Years Old, Per Genotype

    Time frame: 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.

  8. 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

    Time frame: 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.

  9. 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

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Rhythm Pharmaceuticals, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2023
Study completion
2024
First posted
Jul 15, 2021
Registry last updated
Jul 2, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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