Metreleptin for Lipodystrophy

Recruiting at 6 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called Metreleptin to evaluate its safety and effectiveness for people with partial lipodystrophy, a condition where the body doesn't produce enough fat tissue. Metreleptin, administered as a daily injection, helps manage symptoms by replacing missing hormones. This study is for those who participated in the initial study (APG-20) and completed it successfully. Individuals with partial lipodystrophy who were part of the APG-20 study might be suitable candidates for this trial. As a Phase 3 trial, it represents the final step before FDA approval, offering participants a chance to help bring a potentially effective treatment to more patients.

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.

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

Studies have shown that metreleptin is generally well-tolerated in humans. In a previous study with patients who have generalized lipodystrophy, some reported side effects. About 13% of patients experienced low blood sugar, or hypoglycemia. A small number (4%) had reactions at the injection site, such as redness and hives.

The FDA has already approved metreleptin for treating generalized lipodystrophy, indicating its safety for that condition. However, researchers are still studying its safety for partial lipodystrophy. While some evidence suggests safety, more information is needed for this specific use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lipodystrophy?

Metreleptin is unique because it directly targets the hormone leptin, which is often deficient in individuals with lipodystrophy. Unlike other treatments that may focus on managing symptoms like insulin resistance or hyperlipidemia separately, metreleptin addresses the underlying hormonal imbalance. Researchers are excited about this treatment because it offers a more holistic approach by potentially normalizing metabolism and reducing complications associated with lipodystrophy. This could lead to improved overall health outcomes for patients, making it a promising option compared to conventional therapies.

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

Research has shown that metreleptin, which participants in this trial will receive, effectively treats lipodystrophy, a condition where the body can't produce enough fat tissue. It addresses metabolic issues by reducing food intake and enhancing insulin use. One study found that metreleptin treatment significantly improved the quality of life for patients with partial lipodystrophy, with estimated gains in life quality measured at 0.117. Although studies are limited due to the rarity of the condition, existing evidence supports its effectiveness in managing lipodystrophy symptoms. ^{6 7 8 9 10}

Are You a Good Fit for This Trial?

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 not pregnant.

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

Citations

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

The Metreleptin Effectiveness and Safety Registry (MEASuRE) However, it is recognized that the low prevalence of lipodystrophy limits published studies involving metreleptin to small sample sizes.

2. 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 ...

3. 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 ...

4. 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, ...

5. 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 ...

6. myalept.com myalept.com/hcp/safety

Safety | Myalept® (metreleptin) for injection | HCP Six patients (13%) had 7 adverse reactions of hypoglycemia. · Two patients (4%) with generalized lipodystrophy reported injection-site erythema and urticaria.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2014/125390s004lbl.pdf

MYALEPT Label - accessdata.fda.gov The safety of MYALEPT was evaluated in 48 patients with generalized lipodystrophy in a single-arm, open-label study [see Clinical Studies (14.1)]. The ...

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

The Metreleptin Effectiveness and Safety Registry (MEASuRE) One approach to address the paucity of information regarding rare diseases, including lipodystrophy, is to use patient registries—organized ...

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

Metreleptin (Myalept) - Medical Clinical Policy Bulletins Metreleptin is approved by the FDA for treatment of generalized forms of lipodystrophy. In an open-label study, these researchers determined the long-term ...

10. molinahealthcare.com molinahealthcare.com/-/media/Molina/PublicWebsite/PDF/Providers/common/pa-criteria/Myalept-metreleptin-C17341-A.pdf

Myalept (metreleptin) C17341-A • The safety and effectiveness of Myalept for the treatment of complications of partial lipodystrophy have not been established. • The ...