Open-Label Study of Setmelanotide in Hypothalamic Obesity

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

Official Title
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A Phase 2, Open-Label 20-Week Study to Evaluate the Safety and Efficacy of Setmelanotide in Subjects With Hypothalamic Obesity

Conditions
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Hypothalamic Obesity

Intervention / Treatment
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* Drug: Setmelanotide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Setmelanotide<br>Participants received setmelanotide once daily (QD) via SC injection for 16 weeks. All participants initiated treatment with setmelanotide (starting dose being age dependent) and dose escalated up to a maximum dose of 3.0 milligrams (mg) QD. | Drug: Setmelanotide<br>* Setmelanotide for SC injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 5% Reduction in BMI From Baseline After 16 Weeks of Setmelanotide Treatment | BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. Baseline was defined as the most recent measurement prior to the first administration of study drug. | Baseline to 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Percentage of Participants Aged ≥6 to <18 Years With ≥0.2 Reduction of BMI Z-Score or Participants Aged ≥18 Years With 5% Reduction of Body Weight From Baseline After 16 Weeks of Setmelanotide Treatment | For participants aged ≥6 to <18 years, a participant's BMI Z-score was considered for the analysis; for participants ≥18 years, a participant's body weight (kg) was considered for the analysis. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. The BMI Z-score indicated the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score indicates a reduction in BMI from Baseline whereas an increase of BMI-Z score indicates an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug. | Baseline to Week 16 | 
| Percentage of Participants Aged ≥6 to <18 Years With ≥0.2 Reduction of BMI Z-Score From Baseline After 16 Weeks of Setmelanotide Treatment | BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m^2. The BMI Z-score indicated the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score indicates a reduction in BMI from Baseline whereas an increase of BMI-Z score indicates an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug. | Baseline to 16 weeks | 
| Percentage of Participants Aged ≥18 Years With ≥5% Reduction of Body Weight From Baseline After 16 Weeks of Setmelanotide Treatment | Baseline was defined as the most recent measurement prior to the first administration of study drug. | Baseline to Week 16 | 
| Change From Baseline in Waist Circumference in Participants Aged ≥18 Years After 16 Weeks of Setmelanotide Treatment | Waist circumference was measured after participants had fasted for at least 8 hours and at approximately the same time at each visit. Baseline was defined as the most recent measurement prior to the first administration of study drug. | Baseline, Week 16 | 
| Change From Baseline in Daily Hunger Questionnaire Score in Participants Aged <12 Years After 16 Weeks of Setmelanotide Treatment | Daily Hunger Questionnaire for participants <12 years of age: Three aspects of hunger (average hunger in the last 24 hours, most/worst hunger in the last 24 hours, and morning hunger) were assessed daily using a pictorial (smiley face) version of the Likert rating scale with scores from 0 to 4, with 0 = not hungry at all and 4 = hungriest possible. Responses were recorded in the electronic diary. Each of the 3 items (average hunger, most/worst hunger, and morning hunger) was scored separately and averaged to calculate a total score ranging from 0 (not hungry at all) to 4 (hungriest possible) with higher score indicating more hunger. Baseline daily hunger score was calculated as the average of 7 days prior to Baseline visit. | Baseline, Week 16 | 
| Change From Baseline in Daily Hunger Questionnaire Scores in Participants Aged ≥12 Years After 16 Weeks of Setmelanotide Treatment | Daily Hunger Questionnaire for participants ≥12 years of age: Three aspects of hunger (average hunger in the last 24 hours, most/worst hunger in the last 24 hours, and morning hunger) were assessed daily using a numeric rating score for each from 0 to 10, with 0 = not hungry at all and 10 = hungriest possible. The responses to the Daily Hunger Questionnaire were recorded in the electronic diary. Baseline daily hunger score was calculated as the average of 7 days prior to Baseline visit. | Baseline, Week 16 | 
| Number of Participants With Shift From Baseline in Global Hunger Questionnaire Score to Week 16 in Participants Aged < 12 Years | Parents or caregivers of participants <12 years old answered the Caregiver Reported Global Hunger Question for participants who were <12 years old. The following question was asked: How hungry is your child acting now? Possible responses were: Not hungry at all; A little hungry; Moderately hungry; and Extremely hungry. Baseline was defined as the most recent measurement prior to the first administration of study drug. | Baseline, Week 16 | 
| Number of Participants With Shift From Baseline in Global Hunger Questionnaire Score to Week 16 in Participants Aged ≥12 Years | Global Hunger Questionnaire for participants ≥12 years of age. The following question was asked: Overall, how would you rate the hunger you experience now? Possible responses were: No hunger; Mild hunger; Moderate hunger; and Severe hunger. Baseline was defined as the most recent measurement prior to the first administration of study drug. | Baseline, Week 16 | 
| Number of Participants With Adverse Events (AEs) | An AE was defined as any untoward medical occurrence or clinically significant worsening of an existing condition associated with the use of a drug in humans, whether or not considered drug related. An AE (also referred to as an adverse experience) could be any unfavorable and unintended sign (e.g., an abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, without any judgment about causality. | From first dose of study drug up to Day 141 |