Mibavademab for Fat Loss Syndrome

Not currently recruiting at 1 trial location

Overseen By Clinical Trials Administrator

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Must be taking: Metreleptin

Must not be taking: Weight loss drugs, Corticosteroids

Disqualifiers: Malignancy, Heart failure, Low GFR, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, mibavademab, for individuals with Fat Loss Syndrome (GLD) who have used metreleptin without dose changes for at least 6 months. The study aims to determine if mibavademab is safe and tolerable after switching from metreleptin. Researchers also seek to understand possible side effects, how the body processes the drug, and whether the body creates antibodies against it. Individuals with GLD on a stable metreleptin dose and consistent diet and medication for diabetes or cholesterol for the past 3 months may be eligible. As a Phase 3 trial, this study represents the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop your current medications, but it requires that you have been on a stable dose of metreleptin for at least 6 months and have a stable medication regimen for diabetes and/or dyslipidemia for the last 3 months. You cannot be on weight loss medications or high-dose corticosteroids.

Is there any evidence suggesting that mibavademab is likely to be safe for humans?

Research has shown that mibavademab was well-tolerated in past studies. For instance, one study found that mibavademab, also known as REGN4461, was safe for individuals who are overweight or obese with low leptin levels. These participants lost weight, and no major safety issues were reported.

In another study, researchers tested REGN4461, which is similar to mibavademab, and found it to be safe, as it did not cause serious side effects. While these results are encouraging, side effects can still occur. The current study aims to provide more information about the safety of mibavademab for individuals switching from metreleptin treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Mibavademab is unique because it offers a new approach to treating Fat Loss Syndrome by switching patients from metreleptin, which is currently the standard treatment. Unlike metreleptin, which is a leptin replacement therapy, mibavademab works as a monoclonal antibody that targets and modifies specific pathways associated with fat metabolism. Researchers are excited about mibavademab because it has the potential to provide more effective results and possibly fewer side effects than existing hormone-based treatments. This novel mechanism could offer a breakthrough for patients who have not responded well to current options.

What evidence suggests that mibavademab might be an effective treatment for Fat Loss Syndrome?

Research has shown that mibavademab, the investigational treatment in this trial, could help treat Fat Loss Syndrome in people with low leptin levels. One study found that mibavademab can activate the leptin receptor, potentially reducing fat and improving energy use. Another study demonstrated significant weight loss in animals, suggesting it might also benefit humans. Additionally, patients who took high doses of mibavademab for up to a year experienced positive effects, supporting its potential effectiveness. Mibavademab is designed to work even when leptin levels are low, making it a promising option for those who haven't responded to metreleptin. Participants in this trial will switch from at least 6 months of metreleptin therapy to mibavademab. ^{1 4 6 7 8}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for children and adults with Generalized Lipodystrophy who have been on metreleptin treatment for at least 6 months without dose changes in the last 3. They should be able to maintain a stable diet, manage diabetes or dyslipidemia medications alongside metreleptin, and follow study procedures. Self-injection capability or having someone to administer injections is required.

Inclusion Criteria

I have been diagnosed with a liver disease that I was born with or acquired later.

Willing and able to comply with clinic visits and study-related procedures. Participants who are unable/unwilling to self-inject, but are willing to have a capable caregiver inject, are considered eligible

My diet and diabetes or cholesterol medications have been stable for the last 3 months.

Exclusion Criteria

Any physical examination findings and/or history of any illness that, in the opinion of the study investigator, might confound the results of the study or pose an additional risk to the participant by their participation in the study, as defined in the protocol

I haven't had any cancer except for certain skin cancers or localized cervical/anal cancer in the past year.

My kidney function is low, with a GFR under 30 mL/min.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants switch from metreleptin to mibavademab to assess safety and tolerability

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 months

What Are the Treatments Tested in This Trial?

Interventions

• Mibavademab

Trial Overview The trial studies mibavademab's safety when switching from metreleptin in treating GLD. It will assess side effects, monitor mibavademab levels in blood over time, and check if the body creates antibodies against it which might reduce effectiveness or cause side effects.

How Is the Trial Designed?

Group I: mibavademab Experimental Treatment 1 Intervention

Patients switching from at least 6 months of therapy with metreleptin to mibavademab.

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

Published Research Related to This Trial

Targeting fatty acid synthase (FASN) in cancer cells is a promising new approach in cancer therapy, as cancer cells rely heavily on lipids for essential functions.

A new generation of FASN inhibitors, particularly TVB-2640, is progressing into clinical trials, showing potential for effective cancer treatment with improved pharmacologic properties compared to earlier inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Molecular Pathways: Fatty Acid Synthase. Jones, SF., Infante, JR.[2021]

Lipotropes, which are essential nutrients containing methyl groups, significantly reduced the growth of MCF-7 human breast cancer cells and increased apoptosis, indicating potential tumor-suppressive effects.

When combined with chemotherapeutic drugs like SAHA and doxorubicin, lipotropes showed additive effects in inhibiting cell growth, suggesting they could enhance the efficacy of existing cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lipotropes enhance the anti-proliferative effect of chemotherapeutic drugs in MCF-7 human breast cancer cells. Cho, K., Mabasa, L., Walters, MW., et al.[2021]

The FASN inhibitor TVB-3664 demonstrated significant anti-tumor activity in 30% of colorectal cancer patient-derived xenografts (PDXs), indicating its potential effectiveness in treating certain CRC cases.

Treatment with TVB-3664 led to notable changes in tumor lipid composition and reduced activation of key oncogenic pathways (Akt and Erk1/2), suggesting a mechanism of action that could inform personalized treatment strategies for CRC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of novel fatty acid synthase inhibitors in primary colorectal cancer cells and a patient-derived xenograft model of colorectal cancer. Zaytseva, YY., Rychahou, PG., Le, AT., et al.[2022]

GDF15, an adipocyte-secreted factor, has been identified as a key player in promoting resistance to trastuzumab in HER2-positive breast cancer by stimulating PI3K signaling, which reduces the drug's effectiveness.

Inhibition of PI3K can restore sensitivity to trastuzumab, suggesting that targeting GDF15 could be a promising strategy to overcome resistance in patients with HER2-over-expressing metastatic breast cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of Adipocytokine-Mediated Trastuzumab Resistance in HER2-Positive Breast Cancer Cell Lines. Griner, SE., Wang, KJ., Joshi, JP., et al.[2021]

FASN, an enzyme overexpressed in various cancers including melanoma, can be inhibited by drugs like orlistat and cerulenin, leading to reduced melanoma cell proliferation and increased apoptosis.

The apoptosis induced by FASN inhibition occurs through the intrinsic pathway, involving mitochondrial changes and increased reactive oxygen species and calcium levels, but does not depend on p53 activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibition of fatty acid synthase in melanoma cells activates the intrinsic pathway of apoptosis. Zecchin, KG., Rossato, FA., Raposo, HF., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05088460

NCT05088460 | A Study to Examine the Effects of ... Two cohorts are being studied based on leptin levels. Cohort A is composed of patients with baseline leptin <8.0 ng/mL and Cohort B is composed of patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11003274/

Pharmacokinetics and pharmacodynamics of mibavademab ... These results are also consistent with nonclinical findings where mibavademab promoted dramatic weight loss in mice with genetic leptin ...

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

Preclinical, randomized phase 1, and compassionate use ... We developed a fully human monoclonal antibody (mAb), REGN4461 (mibavademab), that activates the human LEPR in the absence or presence of leptin.

4. academic.oup.com academic.oup.com/jes/article/doi/10.1210/jendso/bvaf149.870/8299744

SUN-253 The Impact of Mibavademab, a Novel Leptin ... ... mibavademab from a phase 2 trial (NCT04159415). Here we report safety and efficacy with high-dose mibavademab for up to 52 weeks. Patients ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT07220785

Efficacy and Safety of Mibavademab in Adult and Pediatric ... This study is researching a new drug called mibavademab (called "study drug"). The study involves participants with a condition called ...

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

Preclinical, randomized phase 1, and compassionate use ... In a phase 1, randomized, double-blind, placebo-controlled two-part study, REGN4461 was well tolerated with an acceptable safety profile.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06548100

NCT06548100 | A Study of the Safety of Mibavademab in ... The aim of the study is to see how safe and tolerable mibavademab is when switching from treatment with metreleptin. The study is looking at several other ...

8. clinicaltrials.regeneron.com clinicaltrials.regeneron.com/clinical-trials/a0Mdy00000098XzEAI/nct06548100

A Study of the Safety of Mibavademab in Pediatric and Adult ... This study is researching an experimental drug called mibavademab. The study is focused on participants with GLD who have been on metreleptin treatment for ...