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

Inclusion Criteria:

1. Patients must have a pre-identified genetic variant in an established MC4R pathway gene that contributes to obesity
2. Age 6 to 65 years, inclusive
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
4. Study participant and/or parent or guardian is able to understand all study procedures and provide consent/assent
5. Use of highly effective contraception
6. Symptoms or behaviors of hyperphagia

Exclusion Criteria:

1. 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
2. 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
3. Bariatric surgery within the previous 6 months.
4. Documented diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
5. 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.
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
10. Glomerular filtration rate (GFR) <30 mL/min at Screening
11. History or close family history of melanoma or patient history of oculocutaneous albinism
12. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions
13. Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing
14. Patients previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide
15. Significant hypersensitivity to any excipient in the study drug
16. Females who are breastfeeding or nursing