Clinical trial NCT05774756: A Trial of Setmelanotide in Acquired Hypothalamic Obesity
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Hypothalamic Obesity
Keywords: melancortin 4 receptor, MC4R
Lead sponsor: Rhythm Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2023-03-20
Enrollment: 120
Sex: ALL
Minimum age (years): 4
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 52 weeks on a therapeutic regimen.

A separate sub-study in patients with congenital HO is detailed under NCT06760546.


Eligibility criteria: Key Inclusion Criteria:

1. Documented evidence of acquired hypothalamic obesity (HO)
2. Age 4 years and older
3. 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
4. Agree to use a highly effective form of contraception throughout the study and for 90 days after the study

Key Exclusion Criteria:

1. Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET)
2. 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
3. Bariatric surgery or procedure within last 2 years
4. Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior
5. Current, clinically significant pulmonary, cardiac, metabolic, or oncologic disease
6. Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
7. History or close family history of skin cancer or melanoma
8. Participation in any clinical trial with an investigational drug/device within 3 months prior to the first trial dose
9. Previously enrolled in a clinical trial involving setmelanotide or any previous exposure to setmelanotide
10. Inability to comply with once daily (QD) injection regimen
11. If female, pregnant and/or breastfeeding
12. Patients with obesity attributable to other genetic or syndromic conditions (eg, PPL \[POMC, PCSK1, LEPR, collectively\], BBS) prior to the hypothalamic injury.
13. If receiving hormone replacement therapy, dose has remained stable for at least 2 months before Screening

Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Mean % change in BMI
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
Secondary outcomes:
measure: 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)
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Mean change in the weekly average of the daily most hunger score in patients ≥12 years old
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Proportion of patients with a ≥2 point reduction in the weekly average of the daily most hunger score
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Mean change in Symptoms of Hyperphagia total score
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Proportion of patients with a ≥10% reduction in BMI
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Mean percent change in weight in patients ≥18 years
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Mean BMI-z score and BMI percentile reduction in patients <18 (using combined height and weight to report BMI in kg/m2)
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Proportion of patients aged ≥4 to <18 years with ≥0.2-point reduction of BMI Z-score
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Proportion of patients with BMI <30 kg/m2 (patients aged ≥18 years) or <95th percentile (patients aged <18 years)
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Mean change in physical functioning score and total score for the Impact of Weight on Quality of Life-Lite (IWQOL)
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
measure: Safety and tolerability of setmelanotide compared to placebo assessed by frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: From Baseline after 52 weeks on a therapeutic regimen
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAN Pediatric Endocrinology
state: Alabama
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Chicago
country: United States
facility: Ann and Robert H. Lurie Children's Hospital
state: Illinois
city: Iowa City
country: United States
facility: University of Iowa Stead Family Department of Pediatrics
state: Iowa
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: Saint Paul
country: United States
facility: Children's Minnesota
state: Minnesota
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Irving Medical Center
state: New York
city: Columbus
country: United States
facility: Ohio State Wexner Medical Center
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Health Science Institute
state: Oklahoma
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt University School of Medicine
state: Tennessee
city: Seattle
country: United States
facility: Seattle Children's Hospital, Research and Foundation - Center for Integrative Brain Research
state: Washington
city: Toronto
country: Canada
facility: Hospital for Sick Children
state: Ontario
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf (UKE) - Ambulanzzentrum des UKE GmbH
city: München
country: Germany
facility: Medicover Neuroendokrinologie
city: Oldenburg
country: Germany
facility: University Children's Hospital, Klinikum Oldenburg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm - Klinik fuer Kinder- und Jugendmedizin
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
state: Aichi
city: Azumino City
country: Japan
facility: Nagano Children's Hospital
state: Nagano
city: Minato City
country: Japan
facility: Toranomon Hospital
state: Tokyo
city: Utrecht
country: Netherlands
facility: Prinses Maxima Center for Pediatric Oncology
city: Birmingham
country: United Kingdom
facility: Birmingham Women and Children's Hospital NHS Trust
city: Hull
country: United Kingdom
facility: Hull University Teaching Hospital
city: London
country: United Kingdom
facility: UCL Great Ormond Street Institute of Child Health
Study officials:
affiliation: Rhythm Pharmaceuticals, Inc.
name: David Meeker, MD
role: STUDY_CHAIR
References: