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

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.

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

Conditions:
• Obesity