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

Rhythm Pharmaceuticals

Status and phase: Active, not recruiting; Phase 2

Conditions: Genetic Obesity

Treatments: Drug: Placebo; Drug: Setmelanotide

Study type: Interventional

Funder types: Industry

Identifiers

NCT04963231

RM-493-034

Details and patient eligibility

About

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.

Enrollment: 150 estimated patients

Sex: All

Ages: 6 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Triple Blind

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150 participants in 2 patient groups, including a placebo group

Setmelanotide

Experimental group

Description:

Patients with specific gene variants in the MC4R pathway on setmelanotide

Treatment:

Drug: Setmelanotide

Placebo

Placebo Comparator group

Description:

Patients with specific gene variants in the MC4R pathway on placebo

Treatment:

Drug: Placebo