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DAYBREAK: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway

Primary Purpose

Genetic Obesity

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Setmelanotide
Placebo
Sponsored by
Rhythm Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Genetic Obesity focused on measuring Melanocortin-4 Receptor, Genetic Obesity, Leptin

Eligibility Criteria

6 Years - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must meet all of the following criteria to be eligible for study participation:

    1. Patients must have a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity.
    2. Ages of 6 and 65
    3. Obesity, defined as BMI ≥40 kg/m2 for patients≥18 years of age or BMI ≥97th percentile for age and gender for patients 6 up to 17 years of age based on the US CDC criteria.
    4. Study participant and/or parent or guardian is able to understand all study procedures

    5. Use of highly effective contraception

      Exclusion Criteria:

  • Patients meeting any of the following criteria are not eligible for study participation:

    1. Recent intensive diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that has resulted in weight loss.
    2. Use of any medication that is approved to treat obesity within 3 months of first dose of study drug.
    3. Bariatric surgery within the previous 6 months.
    4. Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s) that the Investigator believes will interfere significantly with study compliance.
    5. Any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) during Screening, any suicide attempt in the past 20 years or any suicidal behavior in the last month.
    6. Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study
    7. Has significant features of (or meets the diagnostic criteria for) a genetic syndrome that is associated with obesity
    8. HbA1C >10.0% at Screening.
    9. History of significant liver disease other than non-alcoholic fatty liver disease (NAFLD) or nonalcoholic steatohepatitis (NASH).
    10. Glomerular filtration rate (GFR) <60 mL/min at Screening.
    11. History or close family history (parents or siblings) of melanoma, or patient history of oculocutaneous albinism.
    12. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
    13. Patient is, in the opinion of the Study Investigator, not suitable to participate in the study.
    14. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
    15. Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
    16. Significant hypersensitivity to any excipient in the study drug.
    17. Females who are breastfeeding or nursing.

Sites / Locations

  • InQuest Medical Reseacrh
  • UMass Memorial Medical Center
  • University of Michigan
  • Metro Detroit Endocrinology Center
  • Mayo Clinic
  • Mississippi Center for Advanced Medicine
  • Mount Sinai
  • Columbia University
  • Ten's Medical Center - Pediatric Endocrinology Clinic
  • University of North Carolina
  • Geisinger Clinic
  • The Children's Hospital of Philadelphia
  • Texas Tech
  • Endocrine Associates of Dallas and Plano
  • Hector Granados PA
  • Texas Children's Hospital
  • Accurate Clinical Research
  • Rio Grande Valley Endocrine Center
  • Clinical Trials of Texas
  • Javara Research
  • University of Alberta
  • Universitaetsklinikum Leipzig
  • Universitaetsklinikum Ulm
  • Chaim Sheba MC, Safra Children's Hospital
  • Erasmus Medisch Centrum
  • Hospital Sant Joan de Deu
  • Hospital Infantil Universitario Nino Jesus
  • Hospital Fundación Jimenez Díaz
  • Hospital General de Valencia
  • University of Cambridge
  • London Medical - The London Diabetes Centre
  • University College London Hospitals NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Setmelanotide

Placebo

Arm Description

Patients with specific gene variants in the MC4R pathway on setmelanotide

Patients with specific gene variants in the MC4R pathway on placebo

Outcomes

Primary Outcome Measures

The proportion of patients by genotype who achieve MC4R pathway who achieve a ≥5% reduction in BMI
To evaluate the proportion of patients with obesity and genetic variants in the MC4R pathway who achieve a clinically meaningful reduction in body weight in response to setmelanotide

Secondary Outcome Measures

Mean change and percent change in BMI in all patients and patients ≥18 years old, per gene
To evaluate change in weight parameters in response to setmelanotide in patients with genetic variants in a specific gene in the MC4R pathway at the end of open-label treatment
Mean change and percent change in body weight in patients ≥18 years old, per gene
To evaluate change in weight parameters in response to setmelanotide in patients with genetic variants in a specific gene in the MC4R pathway at the end of open-label treatment
Mean change in BMI Z-score in patients <18 years old, per gene
To evaluate change in weight parameters in patients less than 18 years of age in response to setmelanotide in patients with genetic variants in a specific gene in the MC4R pathway at the end of open-label treatment
Mean percent change in the weekly average of the daily maximal hunger score in patients ≥12 years old, per gene
To evaluate change in hunger in response to setmelanotide in patients ≥12 years old with genetic variants in a specific gene in the MC4R pathway at the end of open-label treatment
The proportion of patients ≥12 years old, per gene, who achieve a ≥2 point reduction in the weekly average of the daily maximal hunger score
The proportion of patients ≥12 years old, per gene, who achieve a ≥2 point reduction (improvement) in the weekly average of the daily maximal hunger score

Full Information

First Posted
June 28, 2021
Last Updated
July 6, 2023
Sponsor
Rhythm Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04963231
Brief Title
DAYBREAK: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway
Official Title
A Phase 2, Two-Stage (Open-Label Run-in Followed by Randomized Withdrawal), Double-Blind, Placebo-Controlled Study of Setmelanotide in Patients With Specific Gene Variants in the Melanocortin-4 Receptor Pathway
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
November 30, 2021 (Actual)
Primary Completion Date
October 2024 (Anticipated)
Study Completion Date
October 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Rhythm Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No

5. Study Description

Brief Summary
A 2-stage (open-label run-in, followed by randomized, double-blind, placebo-controlled withdrawal) trial of setmelanotide in patients with obesity and specific gene defects variants in the melanocortin-4 receptor (MC4R) pathway.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Genetic Obesity
Keywords
Melanocortin-4 Receptor, Genetic Obesity, Leptin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
Stage 1 of the trial is open-label. Patients who are eligible to enter Stage 2 of the trial will be randomized in a blinded manner at the Stage 2 Entry Visit in a 2:1 ratio to receive either setmelanotide (2) or placebo (1).
Allocation
Randomized
Enrollment
150 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Setmelanotide
Arm Type
Experimental
Arm Description
Patients with specific gene variants in the MC4R pathway on setmelanotide
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Patients with specific gene variants in the MC4R pathway on placebo
Intervention Type
Drug
Intervention Name(s)
Setmelanotide
Intervention Description
Subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Subcutaneous injection
Primary Outcome Measure Information:
Title
The proportion of patients by genotype who achieve MC4R pathway who achieve a ≥5% reduction in BMI
Description
To evaluate the proportion of patients with obesity and genetic variants in the MC4R pathway who achieve a clinically meaningful reduction in body weight in response to setmelanotide
Time Frame
Baseline to End of Stage 1 (16 weeks)
Secondary Outcome Measure Information:
Title
Mean change and percent change in BMI in all patients and patients ≥18 years old, per gene
Description
To evaluate change in weight parameters in response to setmelanotide in patients with genetic variants in a specific gene in the MC4R pathway at the end of open-label treatment
Time Frame
Baseline to End of Stage 1 (16 weeks)
Title
Mean change and percent change in body weight in patients ≥18 years old, per gene
Description
To evaluate change in weight parameters in response to setmelanotide in patients with genetic variants in a specific gene in the MC4R pathway at the end of open-label treatment
Time Frame
Baseline to End of Stage 1 (16 weeks)
Title
Mean change in BMI Z-score in patients <18 years old, per gene
Description
To evaluate change in weight parameters in patients less than 18 years of age in response to setmelanotide in patients with genetic variants in a specific gene in the MC4R pathway at the end of open-label treatment
Time Frame
Baseline to End of Stage 1 (16 weeks)
Title
Mean percent change in the weekly average of the daily maximal hunger score in patients ≥12 years old, per gene
Description
To evaluate change in hunger in response to setmelanotide in patients ≥12 years old with genetic variants in a specific gene in the MC4R pathway at the end of open-label treatment
Time Frame
Baseline to End of Stage 1 (16 weeks)
Title
The proportion of patients ≥12 years old, per gene, who achieve a ≥2 point reduction in the weekly average of the daily maximal hunger score
Description
The proportion of patients ≥12 years old, per gene, who achieve a ≥2 point reduction (improvement) in the weekly average of the daily maximal hunger score
Time Frame
Baseline to End of Stage 1 (16 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients must have a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity Age 6 to 65 years, inclusive Obesity, defined as BMI ≥40 kg/m2 for patients≥18 years of age or BMI ≥97th percentile for age and gender for patients 6 up to 17 years of age Study participant and/or parent or guardian is able to understand all study procedures and provide consent/assent Use of highly effective contraception Symptoms or behaviors of hyperphagia Exclusion Criteria: Patients with the following genetic variants: biallelic Bardet-Biedl Syndrome (BBS); biallelic Alström Syndrome 1 (ALMS1); homozygous, heterozygous, or compound heterozygous variants in MC4R, POMC, PCSK1, 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 include the SH2B1 gene Recent intensive diet and/or exercise regimen with or without the use of weight loss agents including herbal medications that has resulted in weight loss >2% within previous 3 months Bariatric surgery within the previous 6 months. Documented diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s) 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 patient'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 HbA1C >10.0% at Screening History of significant liver disease Glomerular filtration rate (GFR) <30 mL/min at Screening History or close family history of melanoma or patient 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 Patients 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 are breastfeeding or nursing
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Meeker, MD
Organizational Affiliation
Rhythm Pharmaceuticals, Inc.
Official's Role
Study Chair
Facility Information:
Facility Name
InQuest Medical Reseacrh
City
Suwanee
State/Province
Georgia
ZIP/Postal Code
30071
Country
United States
Facility Name
UMass Memorial Medical Center
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48105
Country
United States
Facility Name
Metro Detroit Endocrinology Center
City
Dearborn
State/Province
Michigan
ZIP/Postal Code
48126
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Mississippi Center for Advanced Medicine
City
Madison
State/Province
Mississippi
ZIP/Postal Code
39110
Country
United States
Facility Name
Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia University
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Ten's Medical Center - Pediatric Endocrinology Clinic
City
Staten Island
State/Province
New York
ZIP/Postal Code
10308
Country
United States
Facility Name
University of North Carolina
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27517
Country
United States
Facility Name
Geisinger Clinic
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Facility Name
The Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Texas Tech
City
Amarillo
State/Province
Texas
ZIP/Postal Code
79106
Country
United States
Facility Name
Endocrine Associates of Dallas and Plano
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Hector Granados PA
City
El Paso
State/Province
Texas
ZIP/Postal Code
79907
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Accurate Clinical Research
City
Houston
State/Province
Texas
ZIP/Postal Code
77065
Country
United States
Facility Name
Rio Grande Valley Endocrine Center
City
McAllen
State/Province
Texas
ZIP/Postal Code
78503
Country
United States
Facility Name
Clinical Trials of Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Facility Name
Javara Research
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77382
Country
United States
Facility Name
University of Alberta
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 2E1
Country
Canada
Facility Name
Universitaetsklinikum Leipzig
City
Leipzig
ZIP/Postal Code
04103
Country
Germany
Facility Name
Universitaetsklinikum Ulm
City
Ulm
ZIP/Postal Code
89075
Country
Germany
Facility Name
Chaim Sheba MC, Safra Children's Hospital
City
Ramat Gan
ZIP/Postal Code
5265602
Country
Israel
Facility Name
Erasmus Medisch Centrum
City
Rotterdam
ZIP/Postal Code
3015 GD
Country
Netherlands
Facility Name
Hospital Sant Joan de Deu
City
Barcelona
ZIP/Postal Code
08950
Country
Spain
Facility Name
Hospital Infantil Universitario Nino Jesus
City
Madrid
ZIP/Postal Code
28009
Country
Spain
Facility Name
Hospital Fundación Jimenez Díaz
City
Madrid
ZIP/Postal Code
28040
Country
Spain
Facility Name
Hospital General de Valencia
City
Valencia
ZIP/Postal Code
46014
Country
Spain
Facility Name
University of Cambridge
City
Cambridge
Country
United Kingdom
Facility Name
London Medical - The London Diabetes Centre
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
University College London Hospitals NHS Foundation Trust
City
London
ZIP/Postal Code
WC1E 6JF
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
35797460
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.
Results Reference
derived

Learn more about this trial

DAYBREAK: A Study of Setmelanotide in Patients With Specific Gene Variants in the MC4R Pathway

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