Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT03018678

Enrollment

Registered

2017-01-12

Start date

2016-03-31

Completion date

2019-12-03

Last updated

2020-03-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hypercholesterolemia, Familial

Brief summary

The purpose of this protocol is to identify and screen potential candidates for future enrollment in a gene therapy clinical trial for HoFH.

Detailed description

Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder characterized by markedly elevated LDL-cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset of cardiovascular disease. The most frequent cause is mutation in the LDL receptor gene (LDLR). LDL-C levels remain frequently above acceptable levels despite treatment with multiple existing lipid lowering drugs and/or LDL apheresis. Thus, the functional replacement of the defective LDLR via AAV-based liver-directed gene therapy may be a viable approach to treat this disease and improve response to current lipid-lowering treatments. The purpose of this protocol is to identify and screen potential candidates for future enrollment in a gene therapy clinical trial. No study drug will be administered in this screening study.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* Males and females ≥ 18 years of age * Clinical presentation consistent with homozygous FH * Subjects must be able to comprehend and willing to provide a signed IRB approved Informed Consent Form

Exclusion criteria

* Known to carry confirmed mutations in genes affecting LDL receptor functionality other than the LDLR gene * History of cirrhosis based on documented histological evaluation or non-invasive imaging * Documented diagnosis of any of the following liver diseases: Hepatitis B or C; Biopsy-proven nonalcoholic steatohepatitis; Biopsy-proven alcoholic liver disease; Autoimmune hepatitis; Primary biliary cirrhosis; Primary sclerosing cholangitis; Wilson's disease; Hemochromatosis; alpha1 anti-trypsin deficiency * History of immunodeficiency diseases, including a positive HIV test result * Previous organ transplantation * Serious or unstable medical or psychological conditions that, in the opinion of the investigator, would compromise the subject's safety or successful participation in the study * Inability to participate

Design outcomes

Primary

Measure	Time frame	Description
genetic analysis	Screening phase	identification of genetic, confirmation of FH
Neutralizing antibodies	Screening phase	identification of subjects with no or minimal neutralizing antibodies titer \<= 1:10

Countries

United States

Outcome results