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

NCT06760546 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: RM-493-040-A
• Study Type: interventional
• Target: 39
• Locations: 2 countries
• Sites: 11

Brief Summary

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.

Conditions

Hypothalamic Obesity; Septo-Optic Dysplasia; Multiple Pituitary Hormone Deficiency Genetic Form; Optic Nerve Hypoplasia; Childhood-onset Combined Pituitary Hormone Deficiency; Pituitary Stalk Interruption Syndrome

Keywords

melancortin 4 receptor, MC4R

Outcome Measures

Primary Outcomes (1)

• Mean % change in BMI

  From Baseline after 26 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 26 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 26 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 26 weeks on a therapeutic regimen

• Mean change in Symptoms of Hyperphagia total score

  From Baseline after 26 weeks on a therapeutic regimen

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

  From Baseline after 26 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:

• 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

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

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead

Study Sites (11)

University of Alabama

Birmingham, Alabama, 35233, United States

RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

RECRUITING

Lurie Children's Hospital

Chicago, Illinois, 60611, United States

RECRUITING

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Children's Minnesota

Saint Paul, Minnesota, 55102, United States

RECRUITING

Columbia University Irving Medical Center

New York, New York, 10032, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Seattle Children's Research Institute

Seattle, Washington, 98105, United States

RECRUITING

UCL Great Ormond Street Institute of Child Health

London, Greater London, WC1N 1EH, United Kingdom

RECRUITING

Birmingham Women and Children's Hospital NHS Trust

Birmingham, West Midlands, B46NH, United Kingdom

RECRUITING

Hull Royal Infirmary

Hull, HU32RW, United Kingdom

RECRUITING

Related Links

• This is a sub-study of RM-493-040.

MeSH Terms

Conditions

Sexual Infantilism; Septo-Optic Dysplasia; Optic Nerve Hypoplasia

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; Congenital Cranial Dysinnervation Disorders; Oculomotor Nerve Diseases; Ocular Motility Disorders; Cranial Nerve Diseases; Nervous System Diseases; Agenesis of Corpus Callosum; Nervous System Malformations; Eye Diseases; Optic Nerve Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn

Study Officials

• David Meeker, MD

  Rhythm Pharmaceuticals, Inc.

  STUDY CHAIR

Central Study Contacts

Rhythm Clinical Trials

CONTACT

(857) 264-4280; clinicaltrials@rhythmtx.com

Physician Inquiry Clinical Trials

CONTACT

(857) 264-4280; clinicaltrials@rhythmtx.com

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: December 31, 2024
• First Posted: January 7, 2025
• Study Start: September 23, 2025
• Primary Completion (Estimated): March 13, 2027
• Study Completion (Estimated): March 13, 2028
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); US (8)