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

Prior treatment

• 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
• 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

Other illness

• 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
• Documented diagnosis of current unstable major psychiatric disorder or a documented worsening of psychiatric condition that required changes in treatment within 2 years
• 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
• History of significant liver disease
• History or close family history of melanoma or participant history of oculocutaneous albinism
• Significant hypersensitivity to any excipient in the study drug

Lab values

• Glycated hemoglobin (HbA1C) \>10.0% at Screening
• Glomerular filtration rate (GFR) \<30 milliliter per minute (mL/min) at Screening

Other

• 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.
• Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions
• Females who were breastfeeding or nursing
  • Other protocol defined Inclusion/Exclusion criteria applied.

• 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