LEPR Agonist REGN4461 for Familial Partial Lipodystrophy

(LEAP Trial)

Recruiting at 9 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

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests REGN4461, a medication for managing high blood sugar and fat levels, in patients with low to moderate leptin levels. The treatment aims to improve how the body processes these substances, possibly reducing liver fat and hunger.

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 REGN4461 safe for humans?

In a phase 1 study, REGN4461 was well tolerated and had an acceptable safety profile in humans. ^{1 2 3 4 5}

How does the drug REGN4461 differ from other treatments for familial partial lipodystrophy?

REGN4461 is unique because it is a monoclonal antibody that activates the leptin receptor, potentially improving metabolic issues related to leptin deficiency. Unlike other treatments, it works by directly enhancing leptin signaling, which may help with weight management and metabolic control in patients with lipodystrophy. ^{1 3 6 7 8}

What data supports the effectiveness of the drug REGN4461 for treating Familial Partial Lipodystrophy?

REGN4461, a drug that helps activate the leptin receptor, has shown promise in animal studies by improving body weight, food intake, and blood sugar levels in mice with conditions similar to lipodystrophy. In early human trials, it was well tolerated and helped reduce body weight in people with low leptin levels. ^{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. United States pubmed.ncbi.nlm.nih.gov

Preclinical, randomized phase 1, and compassionate use evaluation of REGN4461, a leptin receptor agonist antibody for leptin deficiency. [2023]

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

Quantitative whole-body MRI in familial partial lipodystrophy type 2: changes in adipose tissue distribution coincide with biochemical improvement. [2018]

3. France pubmed.ncbi.nlm.nih.gov

LMNA gene mutation as a model of cardiometabolic dysfunction: from genetic analysis to treatment response. [2014]

4. Brazil pubmed.ncbi.nlm.nih.gov

[Biochemical, hormonal and genetic evaluation of the families of two Brazilian patients with type 2 familial partial lipodystrophy]. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance. [2022]

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

A recurrent familial partial lipodystrophy due to a monoallelic or biallelic LMNA founder variant highlights the multifaceted cardiac manifestations of metabolic laminopathies. [2022]

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

Serum retinol binding protein 4 in patients with familial partial lipodystrophy. [2009]

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

The complicated clinical course in a case of atypical lipodystrophy after development of neutralizing antibody to metreleptin: treatment with setmelanotide. [2022]