Identifying and Genotyping Homozygous Familial Hypercholesterolemia (HoFH) Patients

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

Detailed Description
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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.

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

Conditions
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Homozygous Familial Hypercholesterolemia (HoFH)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years of age Clinical presentation consistent with HoFH Exclusion Criteria: History of cirrhosis based on documented histological evaluation or noninvasive imaging Documented diagnosis of liver diseases History of immunodeficiency diseases, including a positive HIV test result Previous organ transplantation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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LDL Receptors, Gene Therapy, Metabolic Diseases, Rare Diseases, Genetic Diseases, Atherosclerosis, Cardiovascular Disease, Genotype