Open-Label Study of Setmelanotide in Hypothalamic Obesity

Open-label, single-arm study designed to evaluate the body weight response to setmelanotide administered subcutaneously (SC) daily in participants with hypothalamic obesity (HO).


Eligibility Criteria:
Inclusion Criteria:

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.

Exclusion Criteria:

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.