Identifying and Genotyping Homozygous Familial Hypercholesterolemia (HoFH) Patients

Clinical and Laboratory Assessment Study of Patients With a Clinical Presentation Consistent With Homozygous Familial Hypercholesterolemia (HoFH)

This study is designed to help identify patients with HoFH due to mutations in the LDLR as confirmed by genotyping.

Study Overview

• Status: Completed
• Conditions: Homozygous Familial Hypercholesterolemia (HoFH)

Detailed Description

This is a non-interventional study; no investigational product is administered in this study. Information collected in this study may be used to identify potential participants for clinical gene therapy trials in HoFH.

The investigator will discuss the study with participants who have a clinical presentation consistent with HoFH and where possible, the treating physician, in order to assess their interest to participate. After informed consent has been obtained, participants will be asked to provide a blood sample (up to 40 mL) for genotyping to confirm genetic diagnosis of HoFH due to mutations in LDLR, a lipid panel and anti-AAV8 NAb titer. Participants and, whenever possible, their treating physician will complete a medical history questionnaire and provide supporting documentation. The informed consent form (ICF) and data collection methods may vary depending whether the informed consent is obtained remotely or at a participating study site.

Information collected will include the following:

• patient demographics (age, sex, weight)
• medical history
• previous genotype results (if available)
• results of most recent lipid panel(s)
• use of lipid lowering therapies, including failure to respond
• assessment of presence of liver disease, including history of hepatitis B and C, human immunodeficiency virus (HIV), cirrhosis, and alcohol use

Once this information is received by the investigator and Sponsor, a preliminary assessment of confirmation of a diagnosis of HoFH will be performed. Participants and/or their treating physician will be informed of the results of the genetic testing. All participants will be provided an opportunity to speak with a genetic counselor upon receiving the results of the genetic testing.

Data collected in this study may be used to identify potential candidates for separate clinical trial(s) using gene therapy.

• Study Type: Observational
• Enrollment (Actual): 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials, LLC

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

Males and females ≥ 18 years of age

Description

Inclusion Criteria:

1. Males and females ≥ 18 years of age
2. Clinical presentation consistent with HoFH

Exclusion Criteria:

1. History of cirrhosis based on documented histological evaluation or noninvasive imaging
2. Documented diagnosis of liver diseases
3. History of immunodeficiency diseases, including a positive HIV test result
4. Previous organ transplantation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of participants who have HoFH due to mutations in the LDLR gene measured by genetic testing	The number of participants who have HoFH due to mutations in the LDLR (low density lipoprotein receptor) gene as confirmed by genetic testing.	baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The measurement of AAV8 NAb titers	The measurement of anti-AAV8 (adeno-associated virus serotype 8) neutralizing antibody (NAb) titers	baseline
The measurement of LDL-C, total cholesterol, very low density lipoprotein cholesterol (VLDL-C), non-high density lipoprotein cholesterol (non-HDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), and lipoprotein a (Lp[a])	The measurement of LDL-C, total cholesterol, very low density lipoprotein cholesterol (VLDL-C), non-high density lipoprotein cholesterol (non-HDL-C), high density lipoprotein cholesterol (HDL-C), triglycerides (TG), and lipoprotein a (Lp[a]).	baseline
The number and types of the participant's current and historical lipid lowering therapies	The number and types of lipid lowering therapies, including LDL-C apheresis, the participant has been on or is currently on	baseline
The participant's completion of the medical history questionnaire to determine relevant medical history	Collection of the participant's relevant medical history	baseline

Collaborators and Investigators

• Sponsor: REGENXBIO Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2019
• Primary Completion (Actual): April 8, 2020
• Study Completion (Actual): April 8, 2020

Study Registration Dates

• First Submitted: October 11, 2019
• First Submitted That Met QC Criteria: October 31, 2019
• First Posted (Actual): November 1, 2019

Study Record Updates

• Last Update Posted (Actual): February 2, 2021
• Last Update Submitted That Met QC Criteria: January 28, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Keywords: Gene Therapy; Cardiovascular Disease; Atherosclerosis; Genotype; Rare Diseases; Genetic Diseases; Metabolic Diseases; LDL Receptors
• 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: RGX-501-9101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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