A Long-term Follow-up Study to Evaluate the Safety and Efficacy of RGX-501

Study Overview
=================
Brief Summary
-----------------
This long-term observational study is designed to follow subjects who, during another Clinical Study, received gene therapy treatment used to treat their Homozygous Familial Hypercholesterolemia (HoFH) disease. This study is intended to follow those subjects for up to 5 years since they received treatment to look for any long-term safety concerns. There is no investigational drug or therapy provided as part of this study.

Detailed Description
-----------------
Homozygous Familial Hypercholesterolemia (HoFH) is a rare genetic metabolic disorder characterized by absent or severely reduced capacity to catabolize circulating LDL particles by the hepatic LDL receptor. As a consequence, HoFH subjects present abnormal total plasma cholesterol (LDL-C) levels, resulting in severe atherosclerosis often leading to early onset of cardiovascular disease. Early initiation of aggressive treatment for these patients is therefore essential. Unfortunately, despite existing therapies, treated LDL-C levels could remain well above acceptable levels. Thus, the functional replacement of the defective LDLR via AAV-based liver-directed gene therapy, RGX-501, may be a viable approach to treat this disease and improve response to current lipid-lowering treatments. This is a prospective, observational study to evaluate the long-term safety and efficacy after a single administration of RGX-501. Eligible participants are those who previously have enrolled in a clinical study and received a single intravenous infusion of RGX-501.

Official Title
-----------------
A Long-term Follow-up Study to Evaluate the Safety and Efficacy of RGX-501

Conditions
-----------------
Homozygous Familial Hypercholesterolemia (HoFH)

Intervention / Treatment
-----------------
* Drug: Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: To be eligible to participate in this study, a participant must have previously received RGX-501 in a separate parent trial, and the participant or participant's legal guardian(s) is/(are) willing and able to provide written, signed informed consent after the nature of the study has been explained, prior to any research-related procedures. Exclusion Criteria: None

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RGX-501<br>Study participants who have received RGX-501 gene therapy in a separate parent trial | Drug: Single intravenous (IV) dose of human Low Density Lipoprotein Receptor (LDLR) Gene Therapy<br>* No investigational product will be administered in this study. All participants have previously received a one-time intravenous infusion of RGX-501 in a separate clinical trial<br>* Other names: RGX-501;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of incidents of new and unexpected adverse events and serious adverse events. | The number of times a new and unexpected adverse event and/or serious adverse event is reported. | Up to 5 years after receiving treatment with RGX-501 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The absolute LDL-C level in mg/dL by beta quantification | Absolute LDL-C level by beta quantification at Year 3 after receiving treatment with RGX-501 | Year 3 after receiving treatment with RGX-501 | 
| Absolute total cholesterol, LDL-C, very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), calculated non-HDL-C, triglycerides (TG), and lipoprotein a (Lp(a)) over the study duration | Absolute total cholesterol, LDL-C, very low density lipoprotein cholesterol (VLDL-C), high density lipoprotein cholesterol (HDL-C), calculated non-HDL-C, triglycerides (TG), and lipoprotein a (Lp(a)) over the study duration | Up to 5 years after receiving treatment with RGX-501 | 
| Usage of lipid-lowering therapies over time | Usage of lipid-lowering therapies over time | Up to 5 years after receiving treatment with RGX-501 | 

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