Metreleptin for Partial Lipodystrophy

(METRE-PL Trial)

Not currently recruiting at 59 trial locations

Overseen By Janet Boylan

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Amryt Pharma

Disqualifiers: Previous metreleptin, High leptin, APL, others

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: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called metreleptin for individuals with Familial Partial Lipodystrophy (FPLD), a condition where the body struggles to store fat properly. The goal is to determine if daily metreleptin injections can improve metabolic control, aiding in the management of blood sugar and cholesterol levels. Participants will receive either metreleptin or a placebo to compare effects. Suitable candidates for this trial are those with FPLD who exhibit poor metabolic control, indicated by high blood sugar (HbA1c of 7% or more) or very high triglycerides (500 mg/dL or more), and are already on stable treatment. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants the opportunity to contribute to a potentially groundbreaking treatment.

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 mentions that patients should be on optimized stable therapy. This suggests you may need to continue your current treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that metreleptin has been tested for safety in people with conditions similar to partial lipodystrophy. In earlier studies, patients using metreleptin for other types of lipodystrophy generally tolerated the treatment well. Some experienced mild side effects, such as headaches or minor reactions at the injection site.

Researchers have studied the treatment for long-term safety, examining its effects over extended periods. They found that metreleptin can be safe for long-term use in patients with lipodystrophy. The FDA has approved metreleptin for generalized lipodystrophy, suggesting it is somewhat safe for other types of lipodystrophy as well.

In summary, metreleptin has a history of being well-tolerated with manageable side effects in similar patient groups, providing reassurance for those considering joining the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Metreleptin is unique because it directly addresses the underlying hormone deficiency in partial lipodystrophy by using recombinant-methionyl human leptin. This approach is different from standard treatments that generally focus on managing symptoms like insulin resistance and high triglycerides. Researchers are excited about metreleptin because it targets the root cause of metabolic issues in this condition, potentially offering a more comprehensive and effective solution. Additionally, metreleptin is administered through a daily injection, providing a systematic and consistent approach to hormone replacement therapy.

What evidence suggests that metreleptin might be an effective treatment for Partial Lipodystrophy?

Research has shown that metreleptin, which participants in this trial may receive, can improve well-being in people with partial lipodystrophy. One study found that after 12 months of metreleptin treatment, key health indicators like blood sugar levels, insulin needs, and blood fat levels improved. Another study found that metreleptin aids in metabolic and hormonal issues, such as reducing food intake and enhancing insulin effectiveness. These improvements suggest that metreleptin could be an effective treatment option for managing partial lipodystrophy. ^{3 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for individuals with a condition called Partial Lipodystrophy, specifically those diagnosed with Familial Partial Lipodystrophy (FPLD). It's not open to people who have already been treated with metreleptin.

Inclusion Criteria

I have been diagnosed with Familial Partial Lipodystrophy.

Exclusion Criteria

I have been treated with metreleptin before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daily subcutaneous metreleptin or placebo for 12 months

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• metreleptin
• Placebo

Trial Overview The study is testing the safety and effectiveness of a daily injection of a drug called metreleptin compared to a placebo. This is done in a controlled way where neither the participants nor the researchers know who gets the real treatment or placebo.

How Is the Trial Designed?

Group I: metreleptin Active Control 1 Intervention

Metreleptin \[Recombinant-methionyl human Leptin; r-metHuLeptin\] for daily injection is a sterile, white, solid lyophilised cake

Group II: placebo Placebo Group 1 Intervention

Placebo for daily injection is a sterile, white, solid lyophilised cake

Who Is Running the Clinical Trial?

Amryt Pharma

Lead Sponsor

Trials

9

Recruited

1,000+

Published Research Related to This Trial

In a post-hoc analysis of two phase 2 clinical trials involving patients with generalized and partial lipodystrophy, metreleptin treatment led to significant improvements in HbA1c levels (average decrease of 1.57 percentage points) and fasting triglycerides (median decrease of 37.9%) after 12 months.

The study found that baseline metabolic markers, such as initial HbA1c and triglyceride levels, were significant predictors of improvement, while the use of insulin or lipid-lowering medications at baseline did not significantly affect the outcomes, indicating that metreleptin's efficacy is robust across different patient backgrounds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use. Adamski, K., Cook, K., Gupta, D., et al.[2021]

In a study involving 206 patients (103 treated with metreleptin and 103 matched metreleptin-naïve), metreleptin therapy was associated with a significant 65% reduction in mortality risk for patients with generalized and partial lipodystrophy, indicating its potential life-saving benefits.

Despite the treated patients having more severe metabolic and organ abnormalities, the results suggest that metreleptin has a positive disease-modifying effect, warranting further confirmatory studies in larger populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Leptin Therapy on Survival in Generalized and Partial Lipodystrophy: A Matched Cohort Analysis. Cook, K., Ali, O., Akinci, B., et al.[2022]

In a study involving patients with partial lipodystrophy, metreleptin treatment led to significant improvements in glycemic control, with reductions in HbA1c by 0.6% and fasting triglycerides by 20.8% after 12 months.

Metreleptin was well tolerated, with common side effects including abdominal pain and hypoglycemia, but no unexpected safety issues, indicating it is a safe option for managing metabolic complications in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy. Oral, EA., Gorden, P., Cochran, E., et al.[2022]

In a study of 47 patients with lipodystrophy treated with metreleptin, significant improvements in metabolic outcomes were observed in those with generalized lipodystrophy (GLD), including a notable decrease in glycated hemoglobin (HbA1c) and fasting triglyceride levels after one year of treatment.

While some patients with partial lipodystrophy (PLD) showed initial improvements in triglyceride levels, the overall efficacy of metreleptin in this group was less clear, indicating a need for further clarification on its therapeutic use for PLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic indications and metabolic effects of metreleptin in patients with lipodystrophy syndromes: Real-life experience from a national reference network. Mosbah, H., Vantyghem, MC., Nobécourt, E., et al.[2022]

In a study of 66 patients with generalized lipodystrophy, metreleptin treatment led to significant improvements in metabolic parameters, including a 2.2% reduction in HbA1c and a 32.1% decrease in fasting triglycerides after 12 months.

The treatment was well tolerated, with most adverse events being mild to moderate, and resulted in a notable 33.8% reduction in liver volume, indicating its potential effectiveness in managing complications associated with lipodystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy. Brown, RJ., Oral, EA., Cochran, E., et al.[2023]

In a study of 5 female lipodystrophy patients treated with metreleptin for over 150 weeks, significant improvements in eating behavior were observed, including a marked decrease in hunger and an increase in feelings of satiety after meals.

The long-term treatment resulted in sustained effects, with hunger ratings dropping significantly and measures of cognitive restraint and desire to eat also improving, indicating that metreleptin can effectively regulate appetite over an extended period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial effects of leptin substitution on impaired eating behavior in lipodystrophy are sustained beyond 150 weeks of treatment. Püschel, J., Miehle, K., Müller, K., et al.[2020]

In a study involving 23 patients with partial lipodystrophy, metreleptin treatment led to significant reductions in key metabolic markers such as HbA1c, fasting plasma glucose, and triglycerides over one year, particularly in those with more severe baseline abnormalities.

The treatment was generally well-tolerated, with mild to moderate side effects like nausea and hypoglycemia, and no new safety concerns were identified, suggesting that metreleptin could be a beneficial option for managing metabolic issues in partial lipodystrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program. Ajluni, N., Dar, M., Xu, J., et al.[2020]

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. clinicaltrials.gov clinicaltrials.gov/study/NCT00025883?cond=Lipodystrophy&page=1&rank=10

Study Details | NCT00025883 | Leptin to Treat Lipodystrophy This study will evaluate the safety and effectiveness of leptin replacement therapy in patients with lipodystrophy (also called lipoatrophy).

3. sciencedirect.com sciencedirect.com/science/article/pii/S0003426624000775

Leptin replacement therapy in the management of ... Although consistent data are in favor of positive effects of metreleptin therapy in generalized forms of lipodystrophy, its metabolic benefit seem more variable ...

4. academic.oup.com academic.oup.com/jcem/article/104/8/3068/5371329

Efficacy of Metreleptin Treatment in Familial Partial ... Metreleptin treatment of 12 months led to similar improvements in HbA1c, insulin dose, and triglycerides in patients with familial partial lipodystrophy du.

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT02262832/compassionate-use-of-metreleptin-in-previously-treated-people-with-generalized-lipodystrophy

Compassionate Use of Metreleptin in Previously Treated ... 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/PMC5026130/

Efficacy and Safety of Metreleptin in Patients with Partial ... We aimed to determine the efficacy and safety of metreleptin among patients with partial lipodystrophy using an expanded-access model.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05164341

NCT05164341 | Study to Evaluate the Safety and Efficacy ... This is a Phase III, double-blind, placebo-controlled, safety and efficacy study of daily SC metreleptin in subjects with Partial Lipodystrophy.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT00025883

Study Details | NCT00025883 | Leptin to Treat Lipodystrophy This study will evaluate the safety and effectiveness of leptin replacement therapy in patients with lipodystrophy (also called lipoatrophy).

9. trial.medpath.com trial.medpath.com/clinical-trial/8fac07c31fdb24ba/nct02654977-clinical-protocol-recombinant-human-leptin-lipodystrophy

CLINICAL PROTOCOL to Investigate the Long-term Safety ... The study investigators' aim is to determine the long term safety and efficacy of Metreleptin (Myalept,) in promoting amelioration of metabolic ...