Vanderbilt Clinical Trials

Participants must meet all of the following criteria to be eligible for study participation: - Participant has documented evidence of HO, including: - Recent evidence of hypothalamic injury on magnetic resonance imaging (MRI); AND - Diagnosis of craniopharyngioma or other non-malignant brain tumor affecting the hypothalamic region; AND - Has undergone surgery, or chemotherapy, or radiation ≥6 months and ≤15 years before Screening. - Participant has either unilateral hypothalamic lesions or bilateral hypothalamic lesions, as assessed by MRI. - Obesity, documented by a body mass index (BMI) ≥35 kilograms/square meter (kg/m^2) for participants ≥18 years of age or BMI ≥95th percentile for age and gender for participants 6 to <18 years of age. - Documented increase in BMI (change from pre-surgery baseline in BMI z-score ≥0.2 for participants <18 years of age or BMI >5% for participants >18 years of age) either during the first 6 months following surgery or within 1 year before surgery AND still present at Screening. - More than 6 months after the end of post-tumor treatment, including chemotherapy, surgery, or radiation. - Highly effective contraception throughout the study and for 90 days following the study. - Ability to communicate well with the Investigator, understand and comply with the requirements of the study, and understand and sign the written informed consent, or, for participants aged <18 years, a parent/legal guardian that can sign. - If receiving hormone replacement therapy, the dose of such therapy has remained stable for at least 2 months prior to Screening.

Participants meeting any of the following criteria are not eligible for study participation: - Weight gain >5% in the previous 3 months. - Weight loss ≥2% in the previous 3 months. - Bariatric surgery or procedure within the last 6 months. - Diagnosis of severe psychiatric disorders - Glycated hemoglobin (HbA1c) >10.0% at Screening. - Current, clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results. - Glomerular filtration rate (GFR) <30mL/min/1.73m^2 during Screening. - Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions. - History or close family history (parents or siblings) of skin cancer or melanoma - Participation in any clinical study with an investigational drug/device within 3 months or 5 half-lives, whichever is longer, prior to the first setmelanotide dose. - Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide. - Inability to comply with QD injection regimen. - Pregnant and/or breastfeeding, or desiring to become pregnant during this trial. - Cognitive impairment that, in the Investigator's opinion, precludes participation to the study and completions of study procedures or questionnaires. - Participant is, in Investigator's opinion, otherwise not suitable to participate in the study.