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

NCT06046443 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: LG-MCCL005
• Study Type: interventional
• Target: 28
• Locations: 2 countries
• Sites: 10

Brief Summary

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.

Conditions

Hypothalamic Obesity

Keywords

melanocortin 4 receptor, MC4R; MC4R agonism

Outcome Measures

Primary Outcomes (1)

• Mean percentage change in BMI

  From Baseline to Week 14

Secondary Outcomes (7)

• 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

Study Arms (5)

LB54640 Low dose

EXPERIMENTAL

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

LB54640 Middle dose

EXPERIMENTAL

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

LB54640 High dose

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Open-label LB54640

EXPERIMENTAL

Eligible participants who provide consent to continue into the open-label portion of the study will receive open-label LB54640.

Drug: LB54640

Interventions

LB54640 DRUG

Oral daily administration

LB54640 High dose; LB54640 Low dose; LB54640 Middle dose; Open-label LB54640

Placebo DRUG

Placebo matched to LB54640

Placebo

Eligibility Criteria

• Age: 12 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 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rhythm Pharmaceuticals, Inc.: lead

Study Sites (10)

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

University of Iowa Children's Hospital

Iowa City, Iowa, 52242, United States

Location

Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

Columbia University

New York, New York, 10027, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27514, United States

Location

Lynn Health Science Institute

Oklahoma City, Oklahoma, 73112, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Birmingham Women's and Children's NHS Foundation Trust

Birmingham, B15 2TG, United Kingdom

Location

University of Cambridge

Cambridge, CB2 1TN, United Kingdom

Location

Great Ormond Street Hospital for Children

London, WC1N 3JH, United Kingdom

Location

MeSH Terms

Conditions

Sexual Infantilism

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 2
• 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: September 14, 2023
• First Posted: September 21, 2023
• Study Start: July 11, 2024
• Primary Completion: February 9, 2026
• Study Completion: February 9, 2026
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GB (3); US (7)