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

February 10, 2026 updated by: Rhythm Pharmaceuticals, Inc.

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

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

39

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United Kingdom
      • Hull, United Kingdom, HU32RW
        • Recruiting
        • Hull Royal Infirmary
    • Greater London
      • London, Greater London, United Kingdom, WC1N 1EH
        • Recruiting
        • UCL Great Ormond Street Institute of Child Health
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B46NH
        • Recruiting
        • Birmingham Women and Children's Hospital NHS Trust
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • Recruiting
        • University of Alabama
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Children's Hospital Colorado
    • Illinois
      • Chicago, Illinois, United States, 60611
        • Recruiting
        • Lurie Children's Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Recruiting
        • Boston Children's Hospital
    • Minnesota
      • Saint Paul, Minnesota, United States, 55102
        • Recruiting
        • Children's Minnesota
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
    • Washington
      • Seattle, Washington, United States, 98105
        • Recruiting
        • Seattle Children's Research Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria:

  1. 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
  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. If receiving hormone replacement therapy, dose has remained stable for at least 2 months before Screening

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Setemelanotide
Randomized 2:1 (Setmelanotide: Placebo)
Drug: Setmelanotide
Solution for daily subcutaneous injection
Other Names:
  • RM-493
  • Imcivree
Placebo Comparator: Placebo
Randomized 2:1 (Setmelanotide: Placebo)
Drug: Placebo
Placebo matched to setmelanotide for daily subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Mean % change in BMI
Time Frame: From Baseline after 26 weeks on a therapeutic regimen
From Baseline after 26 weeks on a therapeutic regimen

Secondary Outcome Measures

Outcome Measure
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)
Time Frame: From Baseline after 26 weeks on a therapeutic regimen
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
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
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
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
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
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
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
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
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
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
From Baseline after 26 weeks on a therapeutic regimen

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Rhythm Pharmaceuticals, Inc.

Investigators

  • Study Chair: David Meeker, MD, Rhythm Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 23, 2025

Primary Completion (Estimated)

March 13, 2027

Study Completion (Estimated)

March 13, 2028

Study Registration Dates

First Submitted

December 31, 2024

First Submitted That Met QC Criteria

December 31, 2024

First Posted (Actual)

January 7, 2025

Study Record Updates

Last Update Posted (Actual)

February 12, 2026

Last Update Submitted That Met QC Criteria

February 10, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RM-493-040-A

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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