A Trial of Setmelanotide in Acquired Hypothalamic Obesity

NCT05774756 | Active Not Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: RM-493-040
• Study Type: interventional
• Target: 120
• Locations: 6 countries
• Sites: 28

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.

Conditions

Hypothalamic Obesity

Keywords

melancortin 4 receptor, MC4R

Outcome Measures

Primary Outcomes (1)

• Mean % change in BMI

  From Baseline after 52 weeks on a therapeutic regimen

Secondary Outcomes (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)

  From Baseline after 52 weeks on a therapeutic regimen

• Mean change in the weekly average of the daily most hunger score in patients ≥12 years old

  From Baseline after 52 weeks on a therapeutic regimen

• Proportion of patients with a ≥2 point reduction in the weekly average of the daily most hunger score

  From Baseline after 52 weeks on a therapeutic regimen

• Mean change in Symptoms of Hyperphagia total score

  From Baseline after 52 weeks on a therapeutic regimen

• Proportion of patients with a ≥10% reduction in BMI

  From Baseline after 52 weeks on a therapeutic regimen

Study Arms (2)

Setemelanotide

EXPERIMENTAL

Randomized 2:1 (Setmelanotide: Placebo)

Drug: Setmelanotide

Placebo

PLACEBO COMPARATOR

Randomized 2:1 (Setmelanotide: Placebo)

Drug: Placebo

Interventions

Setmelanotide DRUG

Solution for daily subcutaneous injection

Also known as: RM-493, Imcivree

Setemelanotide

Placebo DRUG

Placebo matched to setmelanotide for daily subcutaneous injection

Placebo

Eligibility Criteria

• Age: 4 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead

Study Sites (28)

UAN Pediatric Endocrinology

Birmingham, Alabama, 35233, United States

Location

Rady Children's Hospital

San Diego, California, 92123, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Florida

Gainesville, Florida, 32610-0296, United States

Location

Ann and Robert H. Lurie Children's Hospital

Chicago, Illinois, 60611, United States

Location

University of Iowa Stead Family Department of Pediatrics

Iowa City, Iowa, 52242, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Children's Minnesota

Saint Paul, Minnesota, 55102, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 100029, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Ohio State Wexner Medical Center

Columbus, Ohio, 43203, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73122, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University School of Medicine

Nashville, Tennessee, 37232, United States

Location

Seattle Children's Hospital, Research and Foundation - Center for Integrative Brain Research

Seattle, Washington, 98101, United States

Location

Hospital for Sick Children

Toronto, Ontario, M5G 1X8, Canada

Location

Universitaetsklinikum Hamburg-Eppendorf (UKE) - Ambulanzzentrum des UKE GmbH

Hamburg, 20246, Germany

Location

Medicover Neuroendokrinologie

München, 81667, Germany

Location

University Children's Hospital, Klinikum Oldenburg

Oldenburg, 26133, Germany

Location

Universitaetsklinikum Ulm - Klinik fuer Kinder- und Jugendmedizin

Ulm, 89075, Germany

Location

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

Nagano Children's Hospital

Azumino, Nagano, 399-8288, Japan

Location

Toranomon Hospital

Minato, Tokyo, 105-8470, Japan

Location

Prinses Maxima Center for Pediatric Oncology

Utrecht, 3584CS, Netherlands

Location

Birmingham Women and Children's Hospital NHS Trust

Birmingham, B46NH, United Kingdom

Location

Hull University Teaching Hospital

Hull, HU32RW, United Kingdom

Location

UCL Great Ormond Street Institute of Child Health

London, WC1N 1EH, United Kingdom

Location

MeSH Terms

Conditions

Sexual Infantilism

Interventions

setmelanotide

Condition Hierarchy (Ancestors)

Gonadal Dysgenesis; Disorders of Sex Development; Urogenital Abnormalities; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Gonadal Disorders; Endocrine System Diseases; Hypogonadism

Study Officials

• David Meeker, MD

  Rhythm Pharmaceuticals, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2023
• First Posted: March 20, 2023
• Study Start: April 26, 2023
• Primary Completion: March 18, 2025
• Study Completion (Estimated): April 16, 2027
• Last Updated: July 2, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (16); JP (3); GB (3); CA (1); DE (4); NL (1)