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Trial · Interventional

CompletedPhase 2Results postedRegistry data

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

NCTNCT04963231 (opens ClinicalTrials.gov in a new tab)Other idRM-493-034
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Overview

Status
Completed
Phase
Phase 2
Enrollment
164 participants (actual)
Sponsor
Rhythm Pharmaceuticals, Inc. · Industry
Design
Randomized · Triple masking
Countries
8 countries

United States, Canada, Germany, Greece, Israel, Netherlands, Spain, United Kingdom

Start
30 Nov 2021
Primary completion
4 Aug 2023
Completion
30 Sept 2024
First posted
15 Jul 2021
Last update posted
2 Jul 2025
Conditions
Genetic Obesity

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
20212022202320242025
  1. Ph 2

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

    NCT04963231

    30 Nov 2021 to 30 Sept 2024

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • SetmelanotideDrug
  • PlaceboDrug

Arms3

  • Experimental

    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.

  • Experimental

    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).

  • Placebo comparator

    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).

Primary outcomes1

Outcomes the sponsor listed as primary.

  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

    Registry description

    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(9)

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

    Time frame · Baseline, Week 16

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeCount of participants· Baseline to Week 16

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

GroupValue (Participants)
Stage 1: Setmelanotide (Open-Label)49
Secondary and other outcome results(7)
Secondary outcomeMean· Baseline, Week 16

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

GroupValue (Kg/m^2)Spread
Stage 1: Setmelanotide (Open-Label)45.3389.5526
Secondary outcomeMean· Baseline, Week 16

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

GroupValue (Kg/m^2)Spread
Stage 1: Setmelanotide (Open-Label)48.4648.0877
Secondary outcomeMean· Baseline, Week 16

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

GroupValue (percent change)Spread
Stage 1: Setmelanotide (Open-Label)-4.624.394
Secondary outcomeMean· Baseline, Week 16

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

GroupValue (percent change)Spread
Stage 1: Setmelanotide (Open-Label)-3.954.057
Secondary outcomeMean· Baseline, Week 16

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

GroupValue (Kg)Spread
Stage 1: Setmelanotide (Open-Label)136.0129.815
Secondary outcomeMean· Baseline, Week 16

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

GroupValue (percent change)Spread
Stage 1: Setmelanotide (Open-Label)-3.944.052
Secondary outcomeMean· Baseline, Week 16

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

GroupValue (z-score)Spread
Stage 1: Setmelanotide (Open-Label)2.6490.3708

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
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 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.0 / 1646 / 164160 / 164
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).0 / 350 / 3525 / 35
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).0 / 140 / 1410 / 14

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies1

Studies that cite this trial.

More studies

1 study on this page

Indexing hint: Review · 2022

Progress in pediatric obesity: new and advanced therapies.

Cuda et al. 2022Current opinion in pediatricscited by 11

PMID 35797460DOI 10.1097/mop.0000000000001150PUB-35797460

Full text at the publisher
Publisher page

Other registry references

References listed at the registry that are not in PepBank. They link to PubMed.

  • DerivedTrapp 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. PMID 36722447

Eligibility

Who could join, as posted.

Sex
All
Age
from 6 Years up to 65 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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