Immunogenicity of Metreleptin in Patients With Generalized Lipodystrophy

Study Overview
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Brief Summary
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MYALEPT™ (metreleptin) has been approved as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy (MYALEPT Prescribing Information). This study is a multicenter, open-label, Phase 4 trial to provide an assessment of the immunogenicity associated with metreleptin and of any major potential risks due to development of antibodies to metreleptin. The study is being conducted to comply with a postmarketing requirement.

Official Title
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A 36-Month, Multicenter, Open Label Phase 4 Study to Evaluate the Immunogenicity of Daily SC Metreleptin Treatment in Patients With Generalized Lipodystrophy

Conditions
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Generalized Lipodystrophy

Intervention / Treatment
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* Drug: Metreleptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provision of informed consent prior to any study specific procedures. If <18 years of age, has a parent or guardian able to read, understand, and sign the Informed Consent Form (ICF) and a Child Assent form, communicate with the Investigator, and understand and comply with protocol requirements. Adolescent patients must also read and understand the Child Assent Form. If the child is too young or unable to read, then the Child Assent form must be explained to the child. Female and/or male patients ≥1 years of age. Physician-confirmed diagnosis of congenital or acquired generalized lipodystrophy and will begin treatment with MYALEPT for the first time. Negative pregnancy test (urine or serum) for female patients of childbearing potential. Female patients of childbearing potential must be 1 year postmenopausal, surgically sterile, or be willing to use an acceptable method of contraception (an acceptable method of contraception is defined as a barrier method in conjunction with a spermicide) for the duration of the study (from the time they sign consent). In addition, oral contraceptives, approved contraceptive implant, long-term injectable contraception, intrauterine device, or tubal ligation are allowed. Oral contraception alone is not acceptable; additional barrier methods in conjunction with spermicide must be used. Male patients must be surgically sterile or be willing to use an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign consent). Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of metreleptin. Exclusion Criteria: Involvement in the planning and/or conduct of the study (applies to both Aegerion staff and/or staff at the study site.) Previous treatment with metreleptin. Participation in another clinical study with an investigational product during the last 6 months. Patients with prior severe hypersensitivity reactions to metreleptin or to any of the product components. Known to have tested positive for human immunodeficiency virus, are immunocompromised, or are receiving immunomodulatory drugs. Known history of drug or alcohol abuse within 1 year of screening. Creatinine clearance <30 mL/min using institutional standards: e.g., calculated using Cockcroft-Gault formula for patients ≥18 years of age; calculated using Schwartz equation for patients <18 years of age. For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding. Any condition where, in the opinion of the Investigator, participation in this study may pose a significant risk to the patient or could render the patient unable to successfully complete the study.

Ages Eligible for Study
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Minimum Age: 1 Year

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metreleptin<br>Subjects will receive prescribed dosage of metreleptin as indicated in the USPI Patients (males and females) ≤ 40 kg: 0.06mg/kg Male patients > 40 kg: 2.5mg Female patients > 40 kg: 5mg | Drug: Metreleptin<br>* Subjects will receive prescribed dosage of metreleptin as indicated in the USPI<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants who develop anti-metreleptin/leptin antibodies at any timepoint after treatment with metreleptin | Antibody titers are determined by the ADA Binding Assay | Month 36 | 
| Percentage of participants who develop anti-metreleptin/leptin antibodies with neutralizing activity at any timepoint after treatment with metreleptin | In vitro neutralizing activity is determined in samples that tested positive for metreleptin/leptin-antibody by the ADA Binding Assay by two methods: Method A: Cell-Based Assay Method B: Receptor-Binding Assay | Month 36 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of participants with SAEs, AESIs or adverse events leading to discontinuation | Percentage of participants with SAEs, AESIs or adverse events leading to discontinuation | Baseline and Months 1, 2, 4, 6, 9, 12, 18, 24, 30, 36 | 
| Percentage of participants with neutralizing or non-neutralizing antibodies who also show one or several of: a. Significant change of HbA1c b. Significant change of triglycerides c. Concomitant SAEs, AESIs or AEs leading to discontinuation | Percentage of participants with neutralizing or non-neutralizing anti-metroleptin/leptin antibodies who also show one or several of: Significant change of hemoglobin A1c Significant change of triglycerides Concomitant SAEs, AESIs or adverse events leading to discontinuation | Baseline and Months 1, 2, 4, 6, 9, 12, 18, 24, 30, 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immunogenicity, Antibodies, Lipodystrophy