LEPR Agonist REGN4461 for Familial Partial Lipodystrophy

(LEAP Trial)

No longer recruiting at 10 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Metreleptin

Disqualifiers: Generalized lipodystrophy, Acquired lipodystrophy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called REGN4461 for individuals with familial partial lipodystrophy, a condition where the body does not store fat properly. The main goal is to assess how REGN4461 affects triglyceride levels and blood sugar levels. The trial consists of two parts, focusing on different groups based on their leptin levels, a hormone related to fat storage. Suitable candidates have familial partial lipodystrophy, specific leptin levels, and issues with triglycerides or blood sugar. Participants will receive either REGN4461 or a placebo (a non-active substance) during the trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it requires no major changes in your medication regimen in the 3 months before screening. This suggests you should continue your current medications without changes.

Is there any evidence suggesting that this trial's treatment is likely to be safe?

Research has shown that REGN4461 is generally safe for humans. In earlier studies, adults who were overweight or obese with low leptin levels used REGN4461 and tolerated it well, with no major safety issues. Some participants also lost weight, suggesting that the treatment may align well with the body's processes.

In a study with mice that had a condition similar to lipodystrophy, REGN4461 improved several health indicators, such as blood sugar levels and liver fat. While these results are encouraging, human trials are still ongoing to confirm long-term safety and effectiveness in a larger population. Participants in a trial will be closely monitored to ensure safety throughout the process. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lipodystrophy?

REGN4461 is unique because it targets the leptin receptor, which is different from the standard treatments for familial partial lipodystrophy that often focus on managing symptoms through diet or diabetes medications. Unlike other treatments, REGN4461 is designed to directly address the underlying metabolic issues by mimicking leptin, a hormone involved in regulating fat distribution and metabolism. Researchers are excited about this approach because it has the potential to improve metabolic health more effectively and possibly reduce the need for long-term symptom management.

What evidence suggests that REGN4461 might be an effective treatment for familial partial lipodystrophy?

Research has shown that REGN4461, a drug that activates leptin receptors, may help treat conditions caused by low leptin levels. In studies, individuals with low leptin who took REGN4461 lost weight over 12 weeks. This trial will evaluate REGN4461 for familial partial lipodystrophy. Participants in one arm will receive REGN4461 for 24 weeks, while another arm will start with a placebo for 12 weeks before switching to REGN4461 for the remaining 12 weeks. This approach suggests that REGN4461 might help manage conditions like familial partial lipodystrophy by improving high triglycerides and blood sugar levels. The treatment activates the leptin receptor, aiding in the control of fat and sugar in the body. Early results are promising, but further research is needed to confirm these effects universally. ^{1 3 5 6 7}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with familial partial lipodystrophy (FPLD) who have stable body weight and diet, and specific metabolic issues related to glucose and triglycerides. They must not be pregnant or breastfeeding, treated with metreleptin recently, or diagnosed with generalized or acquired lipodystrophy.

Inclusion Criteria

Stable body weight within the 3 months prior to screening (no gain or loss of >5% current weight)

No clinically meaningful change in medication regimen in the 3 months prior to screening as defined in the protocol

I have been diagnosed with familial partial lipodystrophy.

Exclusion Criteria

Pregnant or breastfeeding women

I have not taken metreleptin in the last 3 months.

I have been diagnosed with acquired lipodystrophy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either placebo or REGN4461 for 12 to 24 weeks depending on the study arm

24 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Periodic visits for safety assessments

What Are the Treatments Tested in This Trial?

Interventions

• REGN4461

Trial Overview The trial is testing REGN4461, a LEPR agonist antibody for FPLD patients. It's checking if the drug lowers fasting triglycerides in those with high levels and improves blood sugar control in those with high HbA1c. Patients are split into two groups based on their leptin levels.

How Is the Trial Designed?

Group I: Study Arm 2 Experimental Treatment 1 Intervention

Randomized to receive REGN4461 for 24 weeks

Group II: Study Arm 1 Experimental Treatment 2 Interventions

Randomized to placebo for 12 weeks and then crossover to REGN4461 for 12 weeks

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Citations

1. science.org science.org/doi/10.1126/scitranslmed.add4897

Preclinical, randomized phase 1, and compassionate use ... These data demonstrate that the LEPR mAb REGN4461 functions as an allosteric agonist of LEPR and does not compete with leptin binding to LEPR.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37992152/

Preclinical, randomized phase 1, and compassionate use ... Treatment of individuals with overweight or obesity with REGN4461 decreased body weight over 12 weeks in those with low circulating leptin ...

3. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0MPr0000005iPRMAY/nct05088460

A Study to Examine the Effects of the Leptin Receptor (LEPR ... A Study to Examine the Effects of the Leptin Receptor (LEPR) Agonist Antibody REGN4461 in Adult Patients With Familial Partial Lipodystrophy (FPLD).

4. aging.networkofcare.org aging.networkofcare.org/sanmateo/CommunityResources/ClinicalTrials/Detail/NCT05088460?keyword=%22Lipodystrophy%22

San Mateo Clinical Trial A Study to Examine the Effects ... A Study to Examine the Effects of the Leptin Receptor (LEPR) Agonist Antibody REGN4461 in Adult Patients With Familial Partial Lipodystrophy (FPLD).

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05088460

NCT05088460 | A Study to Examine the Effects of ... A Study to Examine the Effects of the Leptin Receptor (LEPR) Agonist Antibody REGN4461 in Adult Patients With Familial Partial Lipodystrophy (FPLD) (LEAP).

6. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0Mdy000000199JEAQ/nct05088460

A Study to Examine the Effects of the Leptin Receptor (LEPR ... A study to examine the effects of the leptin receptor (LEPR) agonist antibody REGN4461 in adult patients with familial partial lipodystrophy (FPLD).

7. academic.oup.com academic.oup.com/jes/article/7/Supplement_1/bvad114.070/7290593

FRI059 Long-term Follow-up On Partial Lipodystrophy Treated ... Here we report the long-term follow-up of a 21- year-old female patient with atypical partial lipodystrophy who developed neutralizing ...