Clinical trial NCT03018678: Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
Official title: Screening Protocol for a Gene Therapy Trial in Subjects With Homozygous Familial Hypercholesterolemia
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypercholesterolemia, Familial
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
First posted: 2017-01-12
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with clinical diagnosis compatible with homozygous familial hypercholesterolemia (HoFH)

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.

Eligibility criteria: 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

Primary outcomes:
measure: genetic analysis
timeFrame: Screening phase
measure: Neutralizing antibodies
timeFrame: Screening phase
Secondary outcomes:
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Associate Professor
name: Marina Cuchel, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: