Clinical trial NCT04026178: Immunogenicity of Metreleptin in Patients With Generalized Lipodystrophy
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Generalized Lipodystrophy
Keywords: Immunogenicity
Antibodies
Lipodystrophy
Lead sponsor: Aegerion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-07-19
Enrollment: 10
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of participants who develop anti-metreleptin/leptin antibodies at any timepoint after treatment with metreleptin
timeFrame: Month 36
measure: Percentage of participants who develop anti-metreleptin/leptin antibodies with neutralizing activity at any timepoint after treatment with metreleptin
timeFrame: Month 36
Secondary outcomes:
measure: Percentage of participants with SAEs, AESIs or adverse events leading to discontinuation
timeFrame: Baseline and Months 1, 2, 4, 6, 9, 12, 18, 24, 30, 36
measure: 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
timeFrame: Baseline and Months 1, 2, 4, 6, 9, 12, 18, 24, 30, 36
Other outcomes:
measure: Percentage of participants who show a significant change in hemoglobin A1c
timeFrame: Baseline and Months 1, 2, 4, 6, 9, 12, 18, 24, 30, 36
measure: Percentage of participants who show a significant change in fasting triglycerides
timeFrame: Baseline and Months 1, 2, 4, 6, 9, 12, 18, 24, 30, 36
Locations:
city: Birmingham
country: United States
facility: Univ. Alabama-Birmingham
state: Alabama
city: New Orleans
country: United States
facility: Ochsner Clinic
state: Louisiana
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Columbus
country: United States
facility: Endocrinology Research Associates
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: Childrens Hospital of Philadelphia
state: Pennsylvania
city: Dallas
country: United States
facility: University Texas Southwestern INT
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Aegerion Pharmaceuticals, Inc.
name: Janet Boylan
role: STUDY_DIRECTOR
References: