Setmelanotide in Pediatric Participants With Rare Genetic Diseases of Obesity

NCT04966741 | Completed Phase 3 Results FDA Drug

• 1 other identifier: RM-493-033
• Study Type: interventional
• Target: 12
• Locations: 4 countries
• Sites: 6

Brief Summary

This is a phase 3 open-label, clinical study to evaluate the efficacy, safety and tolerability of setmelanotide over 1 year of treatment, in pediatric participants aged 2 to \<6 years with obesity due to either biallelic variants of the pro-opiomelanocortin (POMC), proprotein convertase subtilisin/kexin type 1 (PCSK1) or leptin receptor (LEPR) genes or Bardet-Biedl Syndrome (BBS).

Conditions

Bardet-Biedl Syndrome; POMC Deficiency Obesity; PCSK1 Deficiency Obesity; LEPR Deficiency Obesity

Keywords

Bardet Biedl Syndrome; POMC Deficiency; PCSK1; LEPR; Obesity; Pediatric Obesity

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Greater Than or Equal to (≥) 0.2 Reduction of BMI Z-Score From Baseline to Week 52

  A "responder" was defined as a decrease from baseline to 52 weeks in the participant's BMI z-score of ≥0.2. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. The BMI Z-scores were based on the World Health Organization's Child Growth Standards 2007 and indicated the number of standard deviations away from the mean. A Z-score of 0 was equal to the mean of a reference population (i.e., healthy, age and sex-matched individuals). A decrease of BMI Z-score (\< 0) indicated a reduction in BMI from Baseline whereas an increase of BMI-Z score (\> 0) indicated an increase in BMI from Baseline. Baseline was defined as the most recent measurement prior to the first administration of study drug.

  Baseline up to Week 52

• Mean Percent Change From Baseline in BMI

  Mean percent change from baseline to Week 52 in BMI was reported. BMI was calculated using participant's weight and height assessments, using the following formula: BMI = kg/m\^2. Baseline was defined as the most recent measurement prior to the first administration of study drug.

  Baseline, Week 52

Secondary Outcomes (7)

• Mean Absolute Change From Baseline in BMI Z-score

  Baseline, Week 52

• Mean Change From Baseline in Percent of the 95th Percentile of BMI

  Baseline, Week 52

• Mean Change From Baseline in Bone Age

  Baseline, Week 52

• Number of Participants With Shift From Baseline in Ages & Stages Questionnaires, Third Edition (ASQ-3)

  From Baseline to Week 52

• Change From Baseline in Body Weight

  Baseline, Week 52

Study Arms (2)

Setmelanotide: PPL Group

EXPERIMENTAL

Participants with POMC)/PCSK1/LEPR biallelic mutations collectively referred to as PPL received setmelanotide at a dose of 0.5 milligrams (mg) per day (QD) via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide.

Drug: Setmelanotide

Setmelanotide: BBS Group

EXPERIMENTAL

Participants with BBS received setmelanotide at a dose of 0.5 mg QD via SC injection for 52 weeks. The dose was escalated by increments of 0.5 mg every 2 weeks, if tolerated, at the dose escalation visits (Weeks 2, 4, and 6) to a maximum dose of 0.5 to 2.0 mg QD with the maximum dose based on body weight. Following the last dose in this study, participants who were considered likely to benefit from continued setmelanotide treatment and who had completed this trial could be eligible to enter an open-label long-term extension (LTE) trial with setmelanotide.

Drug: Setmelanotide

Interventions

Setmelanotide DRUG

SC injection once daily.

Also known as: IMCIVREE

Setmelanotide: BBS Group; Setmelanotide: PPL Group

Eligibility Criteria

• Age: 2 Years - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Participants must have obesity due to either:
• POMC, PCSK1, or LEPR deficiency, confirmed by genetic testing demonstrating biallelic variants that are interpreted as pathogenic, likely pathogenic, or of undetermined significance (VUS) by the American College of Medical Genetics and Genomics criteria (ACMG), or
• BBS confirmed clinical and genetic diagnosis
• Age between 2 to \<6 years at the time of informed consent
• Obesity, defined as body mass index (BMI) ≥97th percentile for age and gender and body weight of at least 15 kilograms (kg) at the time of enrollment.
• Symptoms or behaviors of hyperphagia
• Parent or guardian of study participant is able to understand and comply with the requirements of the study (including QD injection regimen and all other study procedures) and is able to understand and sign the written consent/assent.

You may not qualify if:

• Glycated hemoglobin (HbA1c) \>9.0% at screening
• History of significant liver disease
• Glomerular filtration rate (GFR) \<60 milliliter per minute per 1.73 meter square (mL/min/1.73 m\^2)
• History or close family history of melanoma, or participant history of oculocutaneous albinism.
• Significant dermatologic findings relating to melanoma or pre-melanoma skin lesions (excluding non-invasive basal or squamous cell lesion)
• Participation in any clinical study with an investigational drug/device within 3 months prior to the first day of dosing.
• Previously enrolled in a clinical study involving setmelanotide or any previous exposure to setmelanotide.
• Significant hypersensitivity to any excipient in the study drug.
• Inadequate hepatic function
• Any other uncontrolled endocrine, metabolic or medical condition(s) known to impact body weight

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead

Study Sites (6)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

Columbia University Medical Center, Division of Pediatric Endocrinology, Diabetes and Metabolism

New York, New York, 10032, United States

Location

Marshfield Clinic Research Foundation

Marshfield, Wisconsin, 54449, United States

Location

Sydney Children's Hospital

Randwick, NSW 2031, Australia

Location

Hospital Infantil Niño Jesus

Madrid, 28009, Spain

Location

Addenbrooke's Hospital, Wellcome Trust-MRC Institute of Metabolic Science

Cambridge, CB2 0QQ, United Kingdom

Location

Related Publications (1)

• Argente J, Verge CF, Okorie U, Fennoy I, Kelsey MM, Cokkinias C, Scimia C, Lee HM, Farooqi IS. Setmelanotide in patients aged 2-5 years with rare MC4R pathway-associated obesity (VENTURE): a 1 year, open-label, multicenter, phase 3 trial. Lancet Diabetes Endocrinol. 2025 Jan;13(1):29-37. doi: 10.1016/S2213-8587(24)00273-0. Epub 2024 Nov 13.

  PMID: 39549719 DERIVED

MeSH Terms

Conditions

Bardet-Biedl Syndrome; Proopiomelanocortin Deficiency; Obesity; Pediatric Obesity

Interventions

setmelanotide

Condition Hierarchy (Ancestors)

Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Retinitis Pigmentosa; Eye Diseases, Hereditary; Eye Diseases; Ciliopathies; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Rhythm Clinical Trials
• Organization: Rhythm Pharmaceuticals, Inc.

clinicaltrials@rhythmtx.com

857-264-4280

Study Officials

• David Meeker, MD

  Rhythm Pharmaceuticals, Inc.

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2021
• First Posted: July 19, 2021
• Study Start: March 8, 2022
• Primary Completion: September 18, 2023
• Study Completion: November 8, 2024
• Last Updated: November 27, 2024
• Results First Posted: July 10, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); AU (1); US (3); GB (1)