Open-Label Study of Setmelanotide in Hypothalamic Obesity
Condition: Hypothalamic Obesity
MeSH terms: Obesity
Intervention: Setmelanotide
Intervention description: Setmelanotide for SC injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 18.0
Sex: All
Minimum age: 6 Years
Maximum age: 40 Years
Healthy volunteers: No

Summary:

      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.