Metreleptin for Lipodystrophy

Recruiting at 4 trial locations

Overseen By Lori Hartnett, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 3

Sponsor: Amryt Pharma

Must not be taking: Immunomodulatory drugs

Disqualifiers: HIV, Immunocompromised, eGFR <30, Malignancy, 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: Unknown

15 Participants Needed

Trial Summary

What is the purpose of this trial?

This Phase 3 study is an Open Label Extension of the APG-20 Study To Evaluate the Long-term Safety and Efficacy of Daily Subcutaneous Metreleptin Treatment in Subjects with Partial Lipodystrophy

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 does mention that subjects on oral contraceptives will not be required to discontinue them. It is best to discuss your specific medications with the study team.

How does the drug Metreleptin differ from other treatments for lipodystrophy?

Metreleptin is unique because it is a synthetic form of the hormone leptin, which helps regulate energy balance and fat storage, making it particularly effective for treating lipodystrophy, a condition characterized by abnormal fat distribution. Unlike other treatments, Metreleptin directly addresses the hormone deficiency that contributes to the symptoms of lipodystrophy. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for individuals with Partial Lipodystrophy, specifically those who have already participated in the APG-20 Study. It's designed to assess long-term safety and effectiveness of Metreleptin when taken daily.

Inclusion Criteria

I am postmenopausal, surgically sterile, or I use effective birth control.

Subjects who are willing to follow the dietary restrictions recommended by the Investigator

I am not pregnant.

Exclusion Criteria

Severe hypersensitivity reactions to the study treatment of the Parent study APG-20

I have tested positive for HIV.

I am immunocompromised or taking drugs that affect my immune system.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Open-label Extension

Participants receive daily subcutaneous metreleptin treatment to evaluate long-term safety and efficacy

24 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Metreleptin

Trial Overview The study tests the ongoing effects of a drug called Metreleptin given by daily injection under the skin. As an open-label extension, all participants know they are receiving Metreleptin and there is no comparison group.

Participant Groups

Group I: Metreleptin Experimental Treatment 1 Intervention

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

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?

Amryt Pharma

Lead Sponsor

Trials

9

Recruited

1,000+

Findings from Research

The study developed a new myostatin inhibitor, MID-35, which is a more stable d-peptide compared to the previously studied MIPE-1686, showing equivalent in vitro effectiveness in inhibiting myostatin.

In vivo tests in mice demonstrated that MID-35 significantly increased muscle mass in the tibialis anterior compared to MIPE-1686, suggesting it could be a promising treatment for muscular atrophy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Myostatin Inhibitory d-Peptides to Enhance the Potency, Increasing Skeletal Muscle Mass in Mice. Takayama, K., Hitachi, K., Okamoto, H., et al.[2023]

The synthetic peptide ovine beta-lipotropin-(41--91) was produced with a 5% yield and demonstrated significantly enhanced lipolytic activity, being 5.4 times more effective than natural ovine beta-lipotropin.

In terms of melanotropic activity, the synthetic peptide was 2.4 times more active than ovine beta-lipotropin but only 5% as active as bovine beta-melanotropin, indicating its potential for specific therapeutic applications without significant opiate effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis and biological activity of ovine beta-lipotropin-(41--91)-henkaipentekontapeptide. Lemaire, S., Yamashiro, D., Li, CH.[2019]

A peptide made up of 50 amino acids from ovine beta-lipotropin was successfully synthesized using solid-phase methods, indicating a reliable technique for peptide production.

This synthetic peptide demonstrated lipolytic activity in isolated rabbit fat cells that was approximately six times greater than that of natural beta-lipotropin, suggesting its potential as a more effective agent for fat breakdown.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synthesis of a pentekontapeptide with high lipolytic activity corresponding to the carboxyl-terminal fifty amino acids of ovine beta-lipotropin. Yamashiro, D., Li, CH.[2019]

The amino acid sequence of beta-lipotropin from the ostrich pituitary has been identified as consisting of 79 amino acids, providing valuable information for understanding its structure and function.

Comparative analysis shows significant variability in the NH2-terminal regions of beta-lipotropin, beta-melanotropin, and beta-endorphin, suggesting potential differences in their biological roles across species.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

beta-Lipotropin: primary structure of the hormone from the ostrich pituitary gland. Naudé, RJ., Chung, D., Li, CH., et al.[2019]

A new peptide isolated from human pituitary glands exhibits both lipolytic (fat-reducing) and melanotropic (skin pigment-increasing) properties, with a unique amino acid composition that sets it apart from known hormones.

This peptide shows significant activity in stimulating melanocyte function and is effective in promoting lipolysis in rabbit fat cells, although it has limited effectiveness in human cells and is inactive in rat cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation of a new lipolytic-melanotropic peptide from human pituitary glands. Smith, G., Gilardeau, C., Lis, M., et al.[2016]

References

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

Development of Myostatin Inhibitory d-Peptides to Enhance the Potency, Increasing Skeletal Muscle Mass in Mice. [2023]

2. Denmark pubmed.ncbi.nlm.nih.gov

Synthesis and biological activity of ovine beta-lipotropin-(41--91)-henkaipentekontapeptide. [2019]

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

Synthesis of a pentekontapeptide with high lipolytic activity corresponding to the carboxyl-terminal fifty amino acids of ovine beta-lipotropin. [2019]

4. Denmark pubmed.ncbi.nlm.nih.gov

beta-Lipotropin: primary structure of the hormone from the ostrich pituitary gland. [2019]

5. Canada pubmed.ncbi.nlm.nih.gov

Isolation of a new lipolytic-melanotropic peptide from human pituitary glands. [2016]