Metreleptin for Generalized Lipodystrophy

Not currently recruiting at 1 trial location

Overseen By Rebecca J Brown, M.D.

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Must be taking: Metreleptin

Disqualifiers: HIV, Alcohol abuse, E. coli allergy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: Ongoing

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of metreleptin, a drug that may help individuals with generalized lipodystrophy manage high blood fat levels and insulin resistance, which can lead to diabetes and other health issues. Participants will receive metreleptin injections and undergo various health tests. The trial suits those with generalized lipodystrophy who have previously received metreleptin through NIH studies and cannot access it in their home country. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to the potential availability of a new treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if any of your medications increase your risk during the trial, you might need to stop them.

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

Research has shown that metreleptin is generally safe for people with generalized lipodystrophy. Studies have found that it helps improve issues like insulin resistance and high levels of fats in the blood for these patients.

In a study with 48 patients, metreleptin was well-tolerated, with few serious side effects. The most common minor side effects included headaches and weight loss. Since metreleptin is already approved for treating metabolic problems related to lipodystrophy, this supports its safety.

For those considering joining a trial for metreleptin, previous patients have responded well to it. Always consult a doctor to determine if it’s the right choice. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Metreleptin is unique because it directly addresses the root cause of generalized lipodystrophy by supplementing leptin, a hormone that people with this condition lack. Unlike current treatments that primarily manage symptoms like insulin resistance or high triglycerides, metreleptin targets the hormonal imbalance itself, potentially offering more comprehensive benefits. Researchers are excited because this approach not only helps improve metabolic abnormalities but also offers a more targeted and holistic treatment option for patients with this rare condition.

What evidence suggests that metreleptin might be an effective treatment for generalized lipodystrophy?

Research has shown that metreleptin, the study drug in this trial, works well for people with generalized lipodystrophy. Studies have found that it helps with issues like high blood fat levels and insulin resistance, which can lead to diabetes. Patients using metreleptin experience significant improvements in overall health. It also helps them eat less and improves their bodies' response to insulin. Overall, metreleptin offers significant benefits in managing symptoms of generalized lipodystrophy. ^{2 4 5 6 7}

Who Is on the Research Team?

Rebecca J Brown, M.D.

Principal Investigator

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Are You a Good Fit for This Trial?

This trial is for people aged 6 months and older with generalized lipodystrophy who have used metreleptin in NIH studies but can't get it where they live. It's not for those with current substance abuse, increased risk from other conditions or medications, sensitivity to E. coli proteins, HIV, or if they can access metreleptin locally.

Inclusion Criteria

You have a condition called generalized lipodystrophy.

You cannot get access to metreleptin through approved methods in your home country.

I am at least 6 months old.

Exclusion Criteria

I have HIV or a condition related to HIV that affects my body shape.

I do not have any health conditions or take medications that would increase my risk.

I can get metreleptin through prescription, compassionate use, or a special program.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metreleptin for daily injections, with evaluations approximately every 6-12 months

Ongoing

1 visit every 6-12 months (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with regular blood tests and evaluations

Ongoing

Regular visits with local doctors every 3-6 months

Long-term follow-up

Continued monitoring of long-term efficacy of metreleptin in ameliorating metabolic complications

Indefinite

What Are the Treatments Tested in This Trial?

Interventions

• Metreleptin

Trial Overview The trial tests the safety and effectiveness of metreleptin in treating complications of generalized lipodystrophy like diabetes. Participants will receive regular supplies of the drug for daily injections and undergo various health checks including blood tests and scans at NIH.

How Is the Trial Designed?

Group I: Leptin study drug Experimental Treatment 1 Intervention

Administration of study drug SQ BID

Metreleptin is already approved in United States, Canada for the following indications:

Approved in United States as Myalept for:

• Complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy

Approved in Canada as Myalept for:

• Complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy
• Patients with partial lipodystrophy

Who Is Running the Clinical Trial?

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Lead Sponsor

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

Metreleptin has been approved by the FDA for treating generalized lipodystrophy, indicating its efficacy as a hormone replacement therapy for leptin deficiency, which may also benefit conditions like familial partial lipodystrophy and obesity.

While metreleptin shows promise for broader applications in metabolic diseases, concerns about its safety and potential immunogenicity need to be addressed before it can be widely used for conditions beyond generalized lipodystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives. Tchang, BG., Shukla, AP., Aronne, LJ.[2018]

Metreleptin, a synthetic leptin analog, has been approved by the FDA for treating generalized lipodystrophy and has shown significant efficacy in reversing severe metabolic complications like hyperglycemia and fatty liver disease in patients with leptin deficiency.

While metreleptin is generally safe for daily subcutaneous administration, there are concerns about potential immune complications, such as lymphoma, and further research is needed to understand its long-term effects and the development of anti-leptin antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New advances in the treatment of generalized lipodystrophy: role of metreleptin. Rodriguez, AJ., Mastronardi, CA., Paz-Filho, GJ.[2022]

A 33-year-old woman with a history of T-cell lymphoma in remission was diagnosed with Acquired Generalized Lipodystrophy (AGL) without ever receiving Metreleptin therapy, suggesting that AGL can occur independently of leptin treatment.

The case highlights the uncertainty regarding the causal relationship between leptin therapy and lymphoma development, as the patient developed AGL after her lymphoma treatment, indicating that other factors like chemotherapy may have influenced her condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis of acquired generalized lipodystrophy in a single patient with T-cell lymphoma and no exposure to Metreleptin. Esfandiari, NH., Rubenfire, M., Neidert, AH., et al.[2022]

The MEASuRE registry is collecting long-term safety and effectiveness data on metreleptin, a treatment for metabolic complications in patients with lipodystrophy, involving 85 patients from 15 US and 4 EU sites as of October 2022.

The integration of MEASuRE with the existing European Registry of Lipodystrophies (ECLip) has allowed for efficient data collection and validation, demonstrating that collaboration can enhance patient enrollment and streamline data gathering for new registries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Metreleptin Effectiveness and Safety Registry (MEASuRE): concept, design and challenges. Haymond, MW., Araújo-Vilar, D., Balser, J., et al.[2023]

Metreleptin, a recombinant human leptin analog, has been approved for treating generalized lipodystrophy and has shown significant improvements in metabolic issues like high blood sugar and triglycerides, as well as liver health.

There is emerging evidence that metreleptin may also help with metabolic problems in patients with partial lipodystrophy, although more research is needed to confirm its efficacy in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metreleptin Treatment in Patients with Non-HIV Associated Lipodystrophy. Akinci, G., Akinci, B.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7993583/

Effects of Metreleptin on Patient Outcomes and Quality of Life ... Quality-adjusted life-year gains associated with 12 months of treatment with metreleptin were estimated at 0.313 for generalized and 0.117 for partial ...

2. myalept.com myalept.com/hcp/efficacy

Efficacy | Myalept® (metreleptin) for injection | HCP Effects of Metreleptin on patient outcomes and quality of life in generalized and partial lipodystrophy. J Endocrin Soc. 2021;5(4):1-16. IMPORTANT SAFETY ...

3. academic.oup.com academic.oup.com/jcem/article/110/4/e1051/7675889

Effects of Metreleptin in Patients With Generalized ... Metreleptin was shown to be effective in causing sustained improvement in metabolic abnormalities in patients with generalized lipodystrophy (4-6). However, ...

4. ojrd.biomedcentral.com ojrd.biomedcentral.com/articles/10.1186/s13023-023-02714-5

The Metreleptin Effectiveness and Safety Registry (MEASuRE) Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy. Endocrine. 2018;60(3):479–89 ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT02262832

NCT02262832 | Compassionate Use of Metreleptin in ... This study showed that metreleptin ameliorates metabolic and endocrine abnormalities in lipodystrophy, including reducing food intake, improving insulin ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10214317/

The Metreleptin Effectiveness and Safety Registry (MEASuRE) Metreleptin, a recombinant analog of human leptin, is an approved therapy, adjunct to diet, to treat the metabolic complications of leptin ...

7. aetna.com aetna.com/cpb/medical/data/800_899/0882.html?ref=counterforcehealth.org

Metreleptin (Myalept) - Medical Clinical Policy Bulletins The safety and effectiveness of Myalept were evaluated in an open-label, single-arm study that included 48 patients with congenital or acquired generalized ...