Open-Label Extension Study of Setmelanotide

Open-Label Extension Study of Setmelanotide in Patients With a Rare Genetic, Syndromic or Acquired Disease of the MC4R Pathway

This is an open-label extension study designed to evaluate the long-term safety and tolerability of continued setmelanotide treatment in male and female patients ≥2 years of age who have completed or transitioned from a previous study with setmelanotide for rare genetic, syndromic, or acquired diseases of obesity upstream of the MC4R pathway.

Study Overview

• Status: Enrolling by invitation
• Conditions: Obesity Associated With Defects in Leptin-melanocortin Pathway
• Intervention / Treatment: Drug: Setmelanotide

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Research Institute
  • California
    • San Diego, California, United States, 92123
      • UC San Diego- Rady Children's Hospital
  • Florida
    • Gainesville, Florida, United States, 32611
      • University of Florida at Gainesville
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
    • Saint Paul, Minnesota, United States, 55102
      • Children's Minnesota
  • New York
    • Getzville, New York, United States, 14068
      • University of Buffalo
  • North Carolina
    • Raleigh, North Carolina, United States, 27612
      • M3 Wake Research, Inc
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17821
      • Geisinger Health System
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • WR-ClinSearch
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University School of Medicine
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Research Institute
  • Wisconsin
    • Marshfield, Wisconsin, United States, 54449
      • Marshfield Clinical Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Males and females ≥2 years of age who have completed a previous setmelanotide clinical study and who have a condition or indication for which Rhythm plans further clinical development.
• Agree to use a highly effective form of contraception and follow the study contraception requirements throughout study duration and for 90 days after.
• Demonstrated clinical benefit in the previous setmelanotide study, as determined by the Investigator.

Key Exclusion Criteria:

• Any gene variant, syndromic, or acquired disease for which setmelanotide is currently approved in the United States (i.e., patients eligible for commercial setmelanotide (IMCIVREE®).
• Any new or worsening depression resulting in suicidal thoughts and/or behaviors.
• Discontinuation from a previous setmelanotide study.
• History or close family history (parents or siblings) of melanoma.
• Pregnant and/or breastfeeding women

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Setelanotide (Open-label); Once daily (QD) subcutaneous injection of setmelanotide	Drug: Setmelanotide; Open-label daily injections of setmelanotide; Other Names: RM-493; Imcivree

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and tolerability of setmelanotide assessed by frequency and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs)	Up to 3 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2024
• Primary Completion (Estimated): October 30, 2027
• Study Completion (Estimated): October 30, 2027

Study Registration Dates

• First Submitted: September 10, 2024
• First Submitted That Met QC Criteria: September 13, 2024
• First Posted (Actual): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 4, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: obesity; setmelanotide; RM-493; melanocortin 4 receptor; hypothalamic obesity
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Nutrition Disorders; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Overnutrition; Body Weight; Gonadal Disorders; Congenital Abnormalities; Overweight; Disorders of Sex Development; Urogenital Abnormalities; Gonadal Dysgenesis; Hypogonadism; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity; Sexual Infantilism; setmelanotide
• Other Study ID Numbers: RM-493-042

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