LB54640 for Obesity

Recruiting in Palo Alto (17 mi)

+14 other locations

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: LG Chem

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

What data supports the idea that LB54640 for Obesity is an effective drug?

The available research shows that melanocortin 4 receptor (MC4R) agonists, like LB54640, can help reduce food intake and body weight. Studies on similar drugs have shown that activating MC4R can lead to weight loss in rodent models. This suggests that LB54640, which is a small molecule MC4R agonist, might also be effective in treating obesity by reducing appetite and promoting weight loss. ^{1 2 3 4 5}

What safety data exists for LB54640 for obesity?

The provided research does not directly mention safety data for LB54640 or its other names. The studies focus on the efficacy of melanocortin 4 receptor (MC4R) agonists in activating mutated receptors associated with obesity, but do not provide specific safety data for LB54640. ^{1 3 4 6 7}

Is the drug LB54640 a promising treatment for obesity?

Yes, LB54640 is a promising drug for obesity because it targets the melanocortin 4 receptor (MC4R), which plays a key role in controlling appetite and body weight. Similar drugs have shown success in activating MC4R, even in cases where genetic mutations make it hard for the body to respond to natural signals. This suggests that LB54640 could help people with obesity, especially those with specific genetic conditions. ^{1 2 3 4 8}

Research Team

David Meeker, MD

Principal Investigator

Rhythm Pharmaceuticals, Inc.

Eligibility Criteria

This trial is for individuals aged 12 and older with Hypothalamic Obesity, marked by weight gain after hypothalamic injury. Adults must have a BMI of ≥30 kg/m2, while those under 18 should be at or above the 95th percentile for their age and sex. Participants must agree to use effective contraception during the study and for three months after.

Inclusion Criteria

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

I have gained weight due to a brain injury and my BMI is over 30 if I'm an adult, or over the 95th percentile for my age and sex if I'm under 18.

I have been diagnosed with hypothalamic obesity.

Exclusion Criteria

I have been diagnosed with Prader-Willi syndrome or ROHHADNET.

Fasting glucose level >270 mg/dL

I have lost more than 2% of my weight in the last 3 months.

Treatment Details

Interventions

• LB54640 (Other)

Trial Overview The study tests LB54640's effectiveness in reducing weight, hunger, and improving quality of life in patients with Hypothalamic Obesity compared to a placebo. It involves taking an oral dose daily up to Week 14, with an option to continue until Week 56.

Participant Groups

Group I: Open-label LB54640 Experimental Treatment 1 Intervention

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

Group II: LB54640 Middle dose Experimental Treatment 1 Intervention

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.

Group III: LB54640 Low dose Experimental Treatment 1 Intervention

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.

Group IV: LB54640 High dose Experimental Treatment 1 Intervention

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.

Group V: Placebo Placebo Group 1 Intervention

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Children's Hospital Colorado Aurora, CO

Research Site Boston, MA

Research Site New York, NY

Research Site Chapel Hill, NC

More Trial Locations

Who Is Running the Clinical Trial?

LG Chem

Lead Sponsor

Trials

66

Patients Recruited

33,800+

Rhythm Pharmaceuticals, Inc.

Lead Sponsor

Trials

31

Patients Recruited

10,400+

Findings from Research

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and SAR of potent and orally bioavailable tert-butylpyrrolidine archetype derived melanocortin subtype-4 receptor modulators. Guo, L., Ye, Z., Ujjainwalla, F., et al.[2008]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular determinants of human melanocortin-4 receptor responsible for antagonist SHU9119 selective activity. Yang, Y., Chen, M., Lai, Y., et al.[2021]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel pharmacological MC4R agonists can efficiently activate mutated MC4R from obese patient with impaired endogenous agonist response. Roubert, P., Dubern, B., Plas, P., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Structural analysis of setmelanotide binding to MC4R variants in comparison to wild-type receptor. Hammad, MM., Mohammad, A., Alam-Eldin, N., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Melanocortin-4 receptor agonists for the treatment of obesity. Emmerson, PJ., Fisher, MJ., Yan, LZ., et al.[2019]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular mechanism of the constitutive activation of the L250Q human melanocortin-4 receptor polymorphism. Proneth, B., Xiang, Z., Pogozheva, ID., et al.[2013]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genetic screening for melanocortin-4 receptor mutations in a cohort of Italian obese patients: description and functional characterization of a novel mutation. Santini, F., Maffei, M., Ceccarini, G., et al.[2022]

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional characterization and pharmacological rescue of melanocortin-4 receptor mutations identified from obese patients. Fan, ZC., Tao, YX.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Synthesis and SAR of potent and orally bioavailable tert-butylpyrrolidine archetype derived melanocortin subtype-4 receptor modulators. [2008]

2. United States pubmed.ncbi.nlm.nih.gov

Molecular determinants of human melanocortin-4 receptor responsible for antagonist SHU9119 selective activity. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Novel pharmacological MC4R agonists can efficiently activate mutated MC4R from obese patient with impaired endogenous agonist response. [2013]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Structural analysis of setmelanotide binding to MC4R variants in comparison to wild-type receptor. [2022]

5. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Melanocortin-4 receptor agonists for the treatment of obesity. [2019]

6. England pubmed.ncbi.nlm.nih.gov

Molecular mechanism of the constitutive activation of the L250Q human melanocortin-4 receptor polymorphism. [2013]

7. United States pubmed.ncbi.nlm.nih.gov

Genetic screening for melanocortin-4 receptor mutations in a cohort of Italian obese patients: description and functional characterization of a novel mutation. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Functional characterization and pharmacological rescue of melanocortin-4 receptor mutations identified from obese patients. [2021]