Intervention: Setmelanotide
Trial phase: Phase 2
ATC code: A08AA12
SMILES: [H]N([H])C(=O)[C@@H]1CSSC[C@H](N([H])C(=O)[C@H](CCCN=C(N([H])[H])N([H])[H])N([H])C(C)=O)C(=O)N[C@H](C)C(=O)N[C@@H](Cc2cncn2[H])C(=O)N[C@H](Cc2ccccc2)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](Cc2cn([H])c3ccccc23)C(=O)N1
Sex: All
Age groups: Child | Adult | Older Adult
Healthy volunteers: No
Participants at risk: 32
Group description: Participants with SRC1 mutations received setmelanotide QD via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and the dose was escalated up to a maximum dose of 3.0 mg QD. Participants either continued setmelanotide treatment by enrolling in an extension study (RM-493-022; NCT03651765) immediately following the last dose in this study or if the extension study was not open at the current clinic site, participants continued treatment in the current study for up to 1 year, resulting in treatment duration of up to 16 months.
Eligibility criteria:
Inclusion Criteria:

Participants with the following genotypes and/or clinical assessment:

POMC/PCSK1/LEPR heterozygous - not currently enrolling new participants
POMC/PCSK1/LEPR compound heterozygous (two different mutations in gene) or homozygous deficiency obesity
POMC/PCSK1/LEPR composite heterozygous (two or more mutations in two or more genes) deficiency obesity
SMS
SH2B1 deficiency obesity
Chromosomal rearrangement of the 16p11.2 locus causing obesity
Carboxypeptidase E (CPE) compound heterozygous or homozygous deficiency obesity
Leptin deficiency obesity with loss of response to metreleptin
SRC1 deficiency obesity
MC4R deficiency obesity
Age 6 years and above
Obese, defined as Body Mass Index (BMI) ≥ 30 kilogram per meter square (kg/m^2) for participants ≥16 years of age or BMI≥ 95th percentile for age and gender for participants 6 up to 16 years of age.
Participant and/or parent or guardian is able to understand and comply with the requirements of the study and is able to understand and sign the written informed consent/assent
Female participants of childbearing potential must be confirmed non-pregnant, and agree to use contraception as outlined in the protocol.
Male participants with female partners of childbearing potential must agree to a double barrier method if they become sexually active during the study. Male participants must not donate sperm during and for 90 days following their participation in the study.

Key Exclusion Criteria:

Recent intensive (within 2 months) diet and/or exercise regimen with or without the use of weight loss agents that has resulted in > 2% weight loss.
Use of any medication that is approved to treat obesity within three months of first dose of study drug (e.g., orlistat, lorcaserin, phentermine-topiramate, naltrexone-bupropion).
Gastric bypass surgery within the previous six months or any prior gastric bypass surgery resulting in >10% weight loss durably maintained
Diagnosis of schizophrenia, bipolar disorder, personality disorder, major depressive disorder, or other psychiatric disorder(s)
Suicidal ideation, attempt or behavior
Clinically significant pulmonary, cardiac, or oncologic disease
hemoglobin A1c (HbA1c) > 9.0% at Screening
History of significant liver disease
Glomerular filtration rate (GFR) < 30 milliliter/minute (mL/min) at Screening.
History or close family history of melanoma or participant 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.
Participants previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
Inability to comply with QD injection regimen.
Females who are breastfeeding or nursing.

Other protocol defined Inclusion/Exclusion criteria may apply.