A Study to Assess Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity

A Randomized, Placebo-controlled, Double-Blind Phase 2 Study to Assess Efficacy and Safety of LB54640 in Patients With Hypothalamic Obesity, With an Open-Label Extension

The goal of this study is to determine how well LB54640 works and how safe it is in patients with Hypothalamic Obesity (HO). The study will evaluate the effect of LB54640 on safety, weight reduction, hunger, and quality of life in patients 12 years of age and older with HO. Patients will take an oral daily dose of either LB54640 (low, middle, or high dose) or placebo through Week 14. Eligible patients who consent to continue in the study after Week 14 will take an oral daily dose of LB54640 through Week 56.

Study Overview

• Status: Completed
• Conditions: Hypothalamic Obesity
• Intervention / Treatment: Drug: LB54640; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Birmingham, United Kingdom, B15 2TG
    • Birmingham Women's and Children's NHS Foundation Trust
  • Cambridge, United Kingdom, CB2 1TN
    • University of Cambridge
  • London, United Kingdom, WC1N 3JH
    • Great Ormond Street Hospital for Children
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Children's Hospital
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center
  • New York
    • New York, New York, United States, 10027
      • Columbia University
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • The University of North Carolina at Chapel Hill
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Lynn Health Science Institute
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude Children's Research Hospital

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Documented evidence of acquired hypothalamic obesity (HO)
• Age 12 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 <18 years of age
• Male and female participants agree to follow study contraception requirements and use a highly effective form of contraception throughout the study and for 90 days after the study

Key Exclusion Criteria:

• Weight loss >2% in the previous 3 months for patients ≥18 years of age or >2% reduction in BMI for patients <18 years of age
• History of major surgical procedure within 30 days
• HbA1c >10.9%
• Fasting glucose level >270 mg/dL
• Previous use of MC4R agonists
• Diagnosis of Prader-Willi syndrome (PWS) or Rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor syndrome (ROHHADNET).
• Diagnosis of severe psychiatric disorders; any suicidal ideation, attempt or behavior
• History or close family history of skin cancer or melanoma
• Current clinically significant pulmonary, cardiac, or oncologic disease considered severe enough to interfere with the study and/or confound the results

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LB54640 Low dose; Participants will be randomized to receive LB54640 low dose, middle dose, or high dose, or placebo by oral administration in a 1:1:1:1 ratio.	Drug: LB54640; Oral daily administration
Experimental: LB54640 Middle dose; Participants will be randomized to receive LB54640 low dose, middle dose, or high dose, or placebo by oral administration in a 1:1:1:1 ratio.	Drug: LB54640; Oral daily administration
Experimental: LB54640 High dose; Participants will be randomized to receive LB54640 low dose, middle dose, or high dose, or placebo by oral administration in a 1:1:1:1 ratio.	Drug: LB54640; Oral daily administration
Placebo Comparator: Placebo; Participants will be randomized to receive LB54640 low dose, middle dose, or high dose, or placebo by oral administration in a 1:1:1:1 ratio.	Drug: Placebo; Placebo matched to LB54640
Experimental: Open-label LB54640; Eligible participants who provide consent to continue into the open-label portion of the study will receive open-label LB54640.	Drug: LB54640; Oral daily administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Mean percentage change in BMI	From Baseline to Week 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of adverse events (AEs)		From Baseline to Week 52
Mean change in BMI		Baseline to Weeks 6, 10, 14
Proportion of patients who achieve ≥5% reduction in body weight		Baseline to Week 14
Mean change in the weekly average of the daily most hunger score		Baseline to Week 14
Mean change and mean percentage change from baseline in body weight		From Baseline to Week 52
Mean change and mean percentage change from baseline in waist circumference.		From Baseline to Week 52
Mean change and mean percentage change from baseline in body composition assessed by dual energy x-ray absorptiometry	Fat mass and lean mass will be measured through dual energy x-ray absorptiometry	From Baseline to Week 52

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): July 11, 2024
• Primary Completion (Actual): February 9, 2026
• Study Completion (Actual): February 9, 2026

Study Registration Dates

• First Submitted: September 14, 2023
• First Submitted That Met QC Criteria: September 14, 2023
• First Posted (Actual): September 21, 2023

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: MC4R agonism; melanocortin 4 receptor, MC4R
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Gonadal Disorders; Congenital Abnormalities; Disorders of Sex Development; Urogenital Abnormalities; Gonadal Dysgenesis; Hypogonadism; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Sexual Infantilism
• Other Study ID Numbers: LG-MCCL005

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
• product manufactured in and exported from the U.S.: No