A Long-Term Follow-up Study of Subjects With Gaucher Disease Who Previously Received AVR-RD-02

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, multinational long-term follow-up study to assess the long-term safety and durability of effect of AVR-RD-02 treatment in subjects who previously received AVR-RD-02 treatment (single dose administration).

Detailed Description
-----------------
Subjects who received AVR-RD-02 in the preceding treatment study and who meet all eligibility criteria may participate in the AVRO-RD-02-LTF01 study. For individual participating subjects, the Baseline visit for the AVRO-RD-02-LTF01 study will coincide with the subject's last visit in the preceding treatment study, whenever feasible. Subjects will be asked to return for study visits at approximately 6-month intervals for the first 4 years of the study and then annually thereafter for 10 years (for a total follow-up of 14 years in this study), during which time periodic safety and efficacy assessments will be performed to assess measures of safety, engraftment, and clinical response after AVR-RD-02 treatment.

Official Title
-----------------
A Long-Term Follow-up Study of Subjects With Gaucher Disease Who Previously Received AVR-RD-02

Conditions
-----------------
Type 1 Gaucher Disease

Intervention / Treatment
-----------------
* Other: Safety and efficacy assessments


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subject must have been enrolled and received AVR-RD-02 as single dose administration Subject must be willing and able to provide written informed consent for the AVRO-RD-02-LTF01 study in accordance with applicable regulations and guidelines and to comply with all study visits and procedures. Exclusion Criteria: Subject is currently enrolled in an AVROBIO-sponsored AVR-RD-02 treatment study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 99 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 |
| --- | --- |
| Subjects with Gaucher 1 Disease<br>This is a long-term follow-up study of subjects who previously received AVR-RD-02 (single dose administration) in a preceding treatment study. No investigational product will be administered in this study. | Other: Safety and efficacy assessments<br>* Safety evaluations, disease-specific assessments, and other assessments to monitor for long-term complications of gene therapy intervention<br>* Other names: Gene Therapy Intervention;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline over time in spleen volume as assessed by abdominal Magnetic Resonance Imaging (MRI) |  | Baseline to Year 15 post gene therapy infusion | 
| Baseline over time in liver volume as assessed by abdominal MRI |  | Baseline to Year 15 post gene therapy infusion | 
| Baseline over time in hemoglobin |  | Baseline to Year 15 post gene therapy infusion | 
| Change from Baseline over time in platelet count |  | Baseline to Year 15 post gene therapy infusion | 
| Change from Baseline in plasma lyso-Gb1 levels by liquid chromatography tandem mass spectrometry (LC/MS/MS) |  | Baseline to Year 15 post gene therapy infusion | 
| Incidence of newly-diagnosed malignancy, hematologic disorder, and/or immune related events/immunogenicity |  | Baseline to Year 15 post gene therapy infusion | 
| Number of participants with clinically relevant abnormalities as assessed by vital signs |  | Baseline to Year 15 post gene therapy infusion | 
| Number of participants with clinically relevant abnormalities, as assessed by physical examinations findings |  | Baseline to Year 15 post gene therapy infusion | 
| Number of participants with clinically relevant abnormalities, as assessed by clinical laboratory tests |  | Baseline to Year 15 post gene therapy infusion | 
| Number of participants with clinically relevant abnormalities, as assessed by electrocardiograms (ECGs) |  | Baseline to Year 15 post gene therapy infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline over time in glucocerebrosidase (GCase) GCase enzyme activity level in |  | Baseline to Year 15 post gene therapy infusion | 
| Change from baseline over time in Enzyme Replacement Therapy (ERT) frequency and dosing |  | Baseline to Year 15 post gene therapy infusion | 
| Changes in Gaucher biomarker indices of Gaucher disease in chitotriosidase enzyme activity levels in plasma |  | Baseline to Year 15 post gene therapy infusion | 
| Changes in Gaucher biomarker indices of Gaucher disease in bone marrow burden (BMB) score as assessed by bone MRI |  | Baseline to Year 15 post gene therapy infusion | 
| Changes in Gaucher biomarker indices of Gaucher disease in bone mineral density (BMD) as assessed by dual-energy X-ray absorptiometry (DXA) |  | Baseline to Year 15 post gene therapy infusion | 
| Average Vector Copy Number (VCN) in bone marrow aspirate as assessed by quantitative polymerase chain reaction (qPCR) and/or droplet digital polymerase chain reaction (ddPCR) |  | Baseline to Year 15 post gene therapy infusion | 
| Change from Baseline in anti-GCase total antibodies and subsequent titers by an electrochemiluminescence method |  | Baseline to Year 15 post gene therapy infusion | 
| Changes in Gaucher disease in potential aberrant clonal expansion(s) assessed by performing insertional site analysis (ISA) |  | Baseline to Year 15 post gene therapy infusion | 
| Presence of replication competent lentivirus (RCL) |  | Baseline to Year 15 post gene therapy infusion | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Gaucher, Guard1