Immunogenicity of Metreleptin in Patients With Generalized Lipodystrophy

Generalized Lipodystrophy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04026178
• Other study ID #: AEGR-734-401
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: November 14, 2018
• Est. completion date: April 2025

Study information

• Verified date: March 2024
• Source: Aegerion Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 10
• Est. completion date: April 2025
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year and older

Eligibility

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.

Related Conditions & MeSH terms

• Generalized Lipodystrophy
• Lipodystrophy

Intervention

Drug:
• Metreleptin
Subjects will receive prescribed dosage of metreleptin as indicated in the USPI

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Univ. Alabama-Birmingham	Birmingham	Alabama
United States	Endocrinology Research Associates	Columbus	Ohio
United States	Ohio State University	Columbus	Ohio
United States	University Texas Southwestern INT	Dallas	Texas
United States	Ochsner Clinic	New Orleans	Louisiana
United States	Childrens Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Aegerion Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Primary	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
Primary	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	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
Secondary	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