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

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

Study Overview

• Status: Completed
• Conditions: Hypercholesterolemia, Familial

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.

• Study Type: Observational
• Enrollment (Actual): 21

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with clinical diagnosis compatible with homozygous familial hypercholesterolemia (HoFH)

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Patients with HOFH; No intervention

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Marina Cuchel, MD, PhD, Associate Professor

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): May 30, 2017
• Study Completion (Actual): December 3, 2019

Study Registration Dates

• First Submitted: January 10, 2017
• First Submitted That Met QC Criteria: January 10, 2017
• First Posted (Estimate): January 12, 2017

Study Record Updates

• Last Update Posted (Actual): March 6, 2020
• Last Update Submitted That Met QC Criteria: March 4, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Lipid Metabolism, Inborn Errors; Hyperlipoproteinemias; Hypercholesterolemia; Hyperlipoproteinemia Type II
• Other Study ID Numbers: 822899

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The following entities may use or share information: (1) the investigator for the study and the study team, (2) the University of Pennsylvania Institutional Review Boards (the committees who oversee research on human subjects) and University of Pennsylvania Office of Regulatory Affairs, (3) The University of Pennsylvania Office of Clinical Research (the office which monitors research studies), and (4) authorized members of the University of Pennsylvania and the University of Pennsylvania Health System and School of Medicine workforce who may need to access your information in the performance of their duties (for example: to provide treatment, to ensure integrity of the research, accounting or billing matters, etc).
• IPD Sharing Time Frame: Has been open until 2015. Data is open until decided.
• IPD Sharing Access Criteria: Data will be de-identified prior to sharing with other entities.

Drug and device information, study documents

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