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

• ClinicalTrials.gov Identifier: NCT04963231
• Recruitment Status: Recruiting
• First Posted: July 15, 2021
• Last Update Posted: November 30, 2022
• Sponsor: Rhythm Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Rhythm Pharmaceuticals, Inc.

Tracking Information

• First Submitted Date: June 28, 2021
• First Posted Date: July 15, 2021
• Last Update Posted Date: November 30, 2022
• Actual Study Start Date: November 30, 2021
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 28, 2022)

The proportion of patients by genotype who achieve MC4R pathway who achieve a ≥5% reduction in BMI [ Time Frame: Baseline to End of Stage 1 (16 weeks) ]

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

Original Primary Outcome Measures (submitted: July 14, 2021)

The proportion of obese patients with genetic defects in the MC4R pathway who achieve a clinically meaningful reduction in body weight [ Time Frame: From baseline to End of Treatment, up to 40 weeks. Total participation in the study will last up to 52 weeks, including the Screening Period and the EOS Visit. ]

To evaluate the proportion of obese patients with genetic defects in the MC4R pathway who achieve a clinically meaningful reduction in body weight in response to setmelanotide after an initial response to open-label treatment

Current Secondary Outcome Measures (submitted: November 28, 2022)

• Mean change and percent change in BMI in all patients and patients ≥18 years old, per gene [ Time Frame: Baseline to End of Stage 1 (16 weeks) ]
  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 [ Time Frame: Baseline to End of Stage 1 (16 weeks) ]
  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 [ Time Frame: Baseline to End of Stage 1 (16 weeks) ]
  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 [ Time Frame: Baseline to End of Stage 1 (16 weeks) ]
  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 [ Time Frame: Baseline to End of Stage 1 (16 weeks) ]
  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

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple (Participant, Care Provider, Investigator)
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).

Primary Purpose: Treatment

• Condition: Genetic Obesity

Intervention

• Drug: Setmelanotide
  Subcutaneous injection
• Drug: Placebo
  Subcutaneous injection

Study Arms

• Experimental: Setmelanotide
  Patients with specific gene variants in the MC4R pathway on setmelanotide
  Intervention: Drug: Setmelanotide
• Placebo Comparator: Placebo
  Patients with specific gene variants in the MC4R pathway on placebo
  Intervention: Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: June 14, 2022): 150
• Original Estimated Enrollment (submitted: July 14, 2021): 500
• Estimated Study Completion Date: October 2024
• Estimated Primary Completion Date: October 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Rhythm Clinical Trials; (857) 264-4280; clinicaltrials@rhythmtx.com

Contact: Physician Inquiry: Clinical Trials; (857) 264-4280; clinicaltrials@rhythmtx.com

• Listed Location Countries: Canada, Germany, Israel, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT04963231
• Other Study ID Numbers: RM-493-034
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Rhythm Pharmaceuticals, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Rhythm Pharmaceuticals, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: David Meeker, MD; Rhythm Pharmaceuticals, Inc.

• PRS Account: Rhythm Pharmaceuticals, Inc.
• Verification Date: November 2022