Immunogenicity of Metreleptin in Patients With Generalized Lipodystrophy

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Generalized Lipodystrophy
• Intervention / Treatment: Drug: Metreleptin

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Janet Boylan; Phone Number: +353 1 518 0200; Email: janet.boylan@amrytpharma.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Univ. Alabama-Birmingham
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • Ohio
    • Columbus, Ohio, United States, 43203
      • Ohio State University
    • Columbus, Ohio, United States, 43201
      • Endocrinology Research Associates
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Childrens Hospital of Philadelphia
  • Texas
    • Dallas, Texas, United States, 75390
      • University Texas Southwestern INT
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 months and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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.
2. Female and/or male patients ≥1 years of age.
3. Physician-confirmed diagnosis of congenital or acquired generalized lipodystrophy and will begin treatment with MYALEPT for the first time.
4. Negative pregnancy test (urine or serum) for female patients of childbearing potential.
5. 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.
6. 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).
7. Patients who are blood donors should not donate blood during the study and for 3 months following their last dose of metreleptin.

Exclusion Criteria:

1. Involvement in the planning and/or conduct of the study (applies to both Aegerion staff and/or staff at the study site.)
2. Previous treatment with metreleptin.
3. Participation in another clinical study with an investigational product during the last 6 months.
4. Patients with prior severe hypersensitivity reactions to metreleptin or to any of the product components.
5. Known to have tested positive for human immunodeficiency virus, are immunocompromised, or are receiving immunomodulatory drugs.
6. Known history of drug or alcohol abuse within 1 year of screening.

7. 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.

8. For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
9. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metreleptin; 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; Subjects will receive prescribed dosage of metreleptin as indicated in the USPI

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of participants who show a significant change in hemoglobin A1c	Absolute change of Hemoglobin A1c from baseline level	Baseline and Months 1, 2, 4, 6, 9, 12, 18, 24, 30, 36
Percentage of participants who show a significant change in fasting triglycerides	Percentage change of triglycerides from baseline level	Baseline and Months 1, 2, 4, 6, 9, 12, 18, 24, 30, 36

Collaborators and Investigators

• Sponsor: Aegerion Pharmaceuticals, Inc.
• Investigators: Study Director: Janet Boylan, Aegerion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2018
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: October 30, 2018
• First Submitted That Met QC Criteria: July 17, 2019
• First Posted (Actual): July 19, 2019

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Immunogenicity; Antibodies; Lipodystrophy
• Additional Relevant MeSH Terms: Metabolic Diseases; Skin Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Lipid Metabolism, Inborn Errors; Skin Diseases, Metabolic; Lipodystrophy; Lipodystrophy, Congenital Generalized
• Other Study ID Numbers: AEGR-734-401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: only IPD that underly results in a publication
• IPD Sharing Time Frame: A copy of data generated at the study site will be provided to individual sites after the overall publication by the sponsor is completed and submitted
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No