Mibavademab for Fat Loss Syndrome

Recruiting at 1 trial location

Overseen By Clinical Trials Administrator

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

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

Pivotal Trial (Near Approval)

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This study is researching an experimental drug called mibavademab. The study is focused on participants with GLD who have been on metreleptin treatment for at least 6 months with no change in dose for the last 3 months. 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 research questions, including: * What side effects may happen from taking mibavademab * How much mibavademab is in the blood at different times * Whether the body makes antibodies against mibavademab (which could make mibavademab less effective or could lead to side effects)

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.

How does the drug Mibavademab differ from other treatments for Fat Loss Syndrome?

Mibavademab is unique because it targets fatty acid synthase (FASN), an enzyme involved in fat production, which is not a common approach for treating Fat Loss Syndrome. This mechanism is more often associated with cancer treatments, where inhibiting FASN can reduce tumor growth. ^{1 2 3 4 5}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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.

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

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

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.

Trial Timeline

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

Treatment Details

Interventions

• Mibavademab (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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]

References

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

Inhibition of fatty acid synthase in melanoma cells activates the intrinsic pathway of apoptosis. [2023]

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

Molecular Pathways: Fatty Acid Synthase. [2021]

3. Greece pubmed.ncbi.nlm.nih.gov

Lipotropes enhance the anti-proliferative effect of chemotherapeutic drugs in MCF-7 human breast cancer cells. [2021]

4. United States 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. [2022]

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

Mechanisms of Adipocytokine-Mediated Trastuzumab Resistance in HER2-Positive Breast Cancer Cell Lines. [2021]