Metreleptin for Partial Lipodystrophy

(METRE-PL Trial)

Recruiting at 55 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

65 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug metreleptin for partial lipodystrophy?

Research shows that metreleptin helps improve eating behavior in lipodystrophy patients by increasing feelings of fullness and reducing hunger, and these benefits last for a long time. ^{1 2 3 4 5}

How is the drug metreleptin unique for treating partial lipodystrophy?

Metreleptin is unique because it is specifically designed to replace leptin, a hormone that helps regulate fat and sugar levels in the body, which is often deficient in people with lipodystrophy. Unlike other treatments, it directly addresses the underlying hormone imbalance rather than just managing symptoms like high blood sugar or cholesterol. ^{1 3 5 6 7}

What is the purpose of this trial?

This trial tests the safety and effectiveness of daily injections of metreleptin for people with Partial Lipodystrophy. The treatment aims to replace a missing hormone to help their bodies manage fat and sugar levels better. Metreleptin is approved by the United States Food and Drug Administration for the treatment of generalized forms of lipodystrophy and has shown improvement in many patients.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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 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 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 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]

References

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

Long-term effectiveness and safety of metreleptin in the treatment of patients with partial lipodystrophy. [2022]

2. England 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. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Beneficial effects of leptin substitution on impaired eating behavior in lipodystrophy are sustained beyond 150 weeks of treatment. [2020]

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

Effect of Leptin Therapy on Survival in Generalized and Partial Lipodystrophy: A Matched Cohort Analysis. [2022]

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

Long-term effectiveness and safety of metreleptin in the treatment of patients with generalized lipodystrophy. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Effects of metreleptin in patients with lipodystrophy with and without baseline concomitant medication use. [2021]

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

Efficacy and Safety of Metreleptin in Patients with Partial Lipodystrophy: Lessons from an Expanded Access Program. [2020]