Metreleptin for Generalized Lipodystrophy

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

30 Participants Needed

Trial Summary

What is the purpose of this trial?

Background: - Generalized lipodystrophy can cause high blood fat levels and resistance to insulin. This can lead to health problems including diabetes. Researchers have found that the drug metreleptin improves health in people with this disease. Objective: - To test the safety and effectiveness of metreleptin. Eligibility: * People ages 6 months and older with generalized lipodystrophy who: * have received metreleptin through NIH studies AND * cannot get it through approved or compassionate use mechanisms in their home country. Design: * Participants will come to NIH approximately every 6 months during year one, then every 1 2 years. Financial assistance may be available for travel within the U.S. * At visits, participants will get a supply of metreleptin to take home for daily injections. They will have: * plastic catheter placed in an arm vein. * blood tests, urine collection, and physical exam. * oral glucose tolerance test, drinking a sweet liquid. * ultrasound of the heart, liver, uterus, and ovaries. A gel and a probe are placed on the skin and pictures are taken of the organs. * echocardiogram, which takes pictures of the heart with sound waves. * Resting Metabolic Rate taken. A plastic hood is worn over the head while the oxygen they breathe is measured. * Participants will have up to 3 DEXA scan x-rays per year. * Participants may have: * annual bone x-rays. * liver biopsies every few years. A needle will be inserted into the liver to obtain a small piece. Participants will sign a separate consent for this. * Participants must be seen regularly by their local doctors and have blood tests at least every 3 6 months at home.

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.

How is the drug metreleptin unique in treating generalized lipodystrophy?

Metreleptin is unique because it is a synthetic version of the hormone leptin, which helps regulate metabolism and is deficient in people with generalized lipodystrophy. It improves metabolic issues like high blood sugar and fat levels, which are common in this condition, and is administered as a daily injection under the skin. ^{1 2 3 4 5}

Research Team

Rebecca J Brown, M.D.

Principal Investigator

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

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

References

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

Metreleptin Treatment in Patients with Non-HIV Associated Lipodystrophy. [2019]

2. England pubmed.ncbi.nlm.nih.gov

The Metreleptin Effectiveness and Safety Registry (MEASuRE): concept, design and challenges. [2023]

3. New Zealand pubmed.ncbi.nlm.nih.gov

New advances in the treatment of generalized lipodystrophy: role of metreleptin. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Diagnosis of acquired generalized lipodystrophy in a single patient with T-cell lymphoma and no exposure to Metreleptin. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives. [2018]