Setmelanotide in Pediatric Patients With Rare Genetic Diseases of Obesity

Study Overview
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Brief Summary
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This is a phase 3 open-label, one-arm, clinical study to evaluate the efficacy, safety and tolerability of setmelanotide over 1 year of treatment, in pediatric patients aged 2 to <6 years with obesity due to either biallelic variants of the POMC, PCSK1 or LEPR genes or Bardet-Biedl Syndrome (BBS).

Detailed Description
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Pediatric patients aged 2 to <6 years with obesity due to either biallelic variants of the POMC, PCSK1 or LEPR genes or Bardet-Biedl Syndrome (BBS) will be enrolled into this phase 3 open-label clinical trial at one of approximately 8 clinical centers in North America, Europe, or Australia. All patients will be assigned to receive setmelanotide via daily subcutaneous injection for 1 year.

Official Title
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A Phase 3 Multi-Center, One-Year, Open-Label Study of Setmelanotide in Pediatric Patients Aged 2 to <6 Years of Age With Rare Genetic Causes of Obesity

Conditions
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Bardet-Biedl Syndrome, POMC Deficiency Obesity, PCSK1 Deficiency Obesity, LEPR Deficiency Obesity

Intervention / Treatment
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* Drug: Setmelanotide


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Patients must have obesity due to either: POMC, PCSK1, or LEPR deficiency, confirmed by genetic testing demonstrating biallelic variants that are interpreted as pathogenic, likely pathogenic, or of undetermined significance (VUS) by the American College of Medical Genetics and Genomics criteria (ACMG), or BBS confirmed clinical and genetic diagnosis Age between 2 to <6 years at the time of informed consent Obesity, defined as BMI ≥97th percentile for age and gender AND body weight of at least 15 kg at the time of enrollment. Symptoms or behaviors of hyperphagia Parent or guardian of study participant is able to understand and comply with the requirements of the study (including once daily [QD] injection regimen and all other study procedures) and is able to understand and sign the written consent/assent. Key Exclusion Criteria HbA1c >9.0% at screening History of significant liver disease Glomerular filtration rate (GFR) <60 mL/min/1.73 m2 History or close family history of melanoma, or patient history of oculocutaneous albinism. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion) Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing. Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide. Significant hypersensitivity to any excipient in the study drug. Inadequate hepatic function Any other uncontrolled endocrine, metabolic or medical condition(s) known to impact body weight Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 5 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>Investigational product: Setmelanotide,10 mg/mL in a sterile solution for Subcutaneous (SC) injection | Drug: Setmelanotide<br>* All patients will begin treatment at a dose of 0.5 mg of setmelanotide per day. Patients will then increase their dose by 0.5 mg increments, every 2 weeks, until reaching their target maximum dose (not to exceed 2mg daily). The target maximum dose of setmelanotide used in this study will be based on the weight bands.<br>* Other names: IMCIVREE;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients demonstrating >0.2 decrease from baseline in body weight | To evaluate the effect of setmelanotide on weight-related parameters by using measurement of decrease in body weight | Baseline to Week 52 | 
| Mean percent change in BMI | To evaluate the effect of setmelanotide on weight-related parameters by using the Body Mass Index measurement | Baseline to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean absolute change from baseline in BMI Z-score | Mean absolute change from baseline in BMI Z-score by age and gender | Baseline to Week 52 | 
| Mean change in percent of the 95th percentile of BMI | Mean change in percent of the 95th percentile of BMI by age and gender | Baseline to Week 52 | 
| Mean change in bone age | Mean change in bone age | Baseline to Week 52 | 
| Mean change in Ages & Stages Questionnaires (ASQ®-3) | Mean change in Ages & Stages Questionnaires score (ASQ®-3) | Baseline to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bardet Biedl Syndrome, POMC Deficiency, PCSK1, LEPR, Obesity, Pediatric Obesity