A Trial of Setmelanotide in Acquired Hypothalamic Obesity

Study Overview
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Brief Summary
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The goal of this trial is to learn how well Setmelanotide works to improve weight reduction, hunger, and quality of life in patients 4 years of age and older with acquired Hypothalamic Obesity (HO). To determine how well setmelanotide works and how safe it is, patients with HO will take a daily injection of either setmelanotide or placebo and complete trial assessments for up to 60 weeks.

Official Title
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A Phase 3, Double Blind, Randomized, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Setmelanotide in Patients With Acquired Hypothalamic Obesity

Conditions
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Hypothalamic Obesity

Intervention / Treatment
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* Drug: Setmelanotide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented evidence of acquired hypothalamic obesity (HO) Age 4 years and older Weight gain associated with the hypothalamic injury and a BMI of ≥30 kg/m2 for patients ≥18 years of age or BMI ≥95th percentile for age and sex for patients 4 to <18 years of age Agree to use a highly effective form of contraception throughout the study and for 90 days after the study Key Exclusion Criteria: Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET) Weight loss >2% in the previous 3 months for patients aged ≥18 years or >2% reduction in BMI for patients aged 4 to <18 years Bariatric surgery or procedure within last 2 years Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion) History or close family history of skin cancer or melanoma Participation in any clinical trial with an investigational drug/device within 3 months prior to the first trial dose Previously enrolled in a clinical trial involving setmelanotide or any previous exposure to setmelanotide Inability to comply with once daily (QD) injection regimen If female, pregnant and/or breastfeeding Patients with obesity attributable to other genetic or syndromic conditions (eg, PPL [POMC, PCSK1, LEPR, collectively], BBS) prior to the hypothalamic injury. If receiving hormone replacement therapy, dose has remained stable for at least 2 months before Screening Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 4 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Setemelanotide<br>Randomized 2:1 (Setmelanotide: Placebo) | Drug: Setmelanotide<br>* Solution for daily subcutaneous injection<br>* Other names: Imcivree;|
| Placebo Comparator: Placebo<br>Randomized 2:1 (Setmelanotide: Placebo) | Drug: Placebo<br>* Placebo matched to setmelanotide for daily subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean % change in BMI |  | From Baseline to Week 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with ≥5% reduction in BMI in adult patients (≥18 years of age) or a BMI Z-score reduction of ≥0.2 points in pediatric patients (<18 years of age) |  | From Baseline to Week 60 | 
| Mean change in the weekly average of the daily most hunger score in patients ≥12 years old |  | From Baseline to Week 60 | 
| Proportion of patients with a ≥2 point reduction in the weekly average of the daily most hunger score |  | From Baseline to Week 60 | 
| Mean change in Symptoms of Hyperphagia total score |  | From Baseline to Week 60 | 
| Proportion of patients with a ≥10% reduction in BMI |  | From Baseline to Week 60 | 
| Mean percent change in weight in patients ≥18 years |  | From Baseline to Week 60 | 
| Mean BMI-z score and BMI percentile reduction in patients <18 (using combined height and weight to report BMI in kg/m2) |  | From Baseline to Week 60 | 
| Proportion of patients aged ≥4 to <18 years with ≥0.2-point reduction of BMI Z-score |  | From Baseline to Week 60 | 
| Proportion of patients with BMI <30 kg/m2 (patients aged ≥18 years) or <95th percentile (patients aged <18 years) |  | From Baseline to Week 60 | 
| Mean change in physical functioning score and total score for the Impact of Weight on Quality of Life-Lite (IWQOL) |  | From Baseline to Week 60 | 
| Safety and tolerability of setmelanotide compared to placebo assessed by frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | From Baseline to Week 60 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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melancortin 4 receptor, MC4R