A Trial of Setmelanotide in Patients With Congenital Hypothalamic Obesity (Sub-study of NCT05774756)

Official title

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

Overview

This is a sub-study of Study RM-493-040 (NCT05774756). The goal of this sub-study 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 congenital Hypothalamic Obesity (cHO). To determine how well setmelanotide works and how safe it is, patients with cHO will take a daily injection of either setmelanotide or placebo and complete trial assessments for up to 26 weeks on a therapeutic regimen.

Interventions

• Drug Setmelanotide
  Solution for daily subcutaneous injection
• Drug Placebo
  Placebo matched to setmelanotide for daily subcutaneous injection

Primary outcome measures

• Mean % change in BMI [Time frame: From Baseline after 26 weeks on a therapeutic regimen]

Secondary outcome measures (11)

• 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) [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Mean change in the weekly average of the daily most hunger score in patients ≥12 years old [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Proportion of patients with a ≥2 point reduction in the weekly average of the daily most hunger score [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Mean change in Symptoms of Hyperphagia total score [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Proportion of patients with a ≥10% reduction in BMI [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Mean percent change in weight in patients ≥18 years [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Mean BMI-z score and BMI percentile reduction in patients <18 (using combined height and weight to report BMI in kg/m2) [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Proportion of patients aged ≥4 to <18 years with ≥0.2-point reduction of BMI Z-score [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Proportion of patients with BMI <30 kg/m2 (patients aged ≥18 years) or <95th percentile (patients aged <18 years) [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Mean change in physical functioning score and total score for the Impact of Weight on Quality of Life-Lite (IWQOL) [Time frame: From Baseline after 26 weeks on a therapeutic regimen]
• Safety and tolerability of setmelanotide compared to placebo assessed by frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) [Time frame: From Baseline after 26 weeks on a therapeutic regimen]

Eligibility criteria

Inclusion criteria

• Diagnosis of multiple pituitary hormone deficiency (MPHD), or septo-optic dysplasia (SOD), or optic nerve hypoplasia (ONH), or Childhood-onset combined pituitary hormone deficiency (CPHD), or Pituitary Stalk Interruption Syndrome (PSIS) with at least one pituitary deficiency AND a body mass index (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
• 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

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.
• If receiving hormone replacement therapy, dose has remained stable for at least 2 months before Screening

Other protocol defined Inclusion/Exclusion criteria may apply.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 8 centers

• University of Alabama — Birmingham
• Children's Hospital Colorado — Aurora
• Lurie Children's Hospital — Chicago
• Boston Children's Hospital — Boston
• Children's Minnesota — Saint Paul
• Columbia University Irving Medical Center — New York
• Children's Hospital of Philadelphia — Philadelphia
• Seattle Children's Research Institute — Seattle

United Kingdom · 3 centers

• UCL Great Ormond Street Institute of Child Health — London
• Birmingham Women and Children's Hospital NHS Trust — Birmingham
• Hull Royal Infirmary — Hull

Identifiers

NCT: NCT06760546 · RM-493-040-A

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗