Long-Term Follow-up Study of Subjects With Fabry Disease Who Received Lentiviral Gene Therapy in Study AVRO-RD-01-201

Study Overview
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Brief Summary
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This is a multinational, long-term follow-up study to assess the long-term safety and durability of AVR-RD-01 treatment in participants who received a single dose administration of lentiviral gene therapy in Study AVRO-RD-01-201 (treatment study). No investigational product will be administered in this study. Participants will continue periodic safety and efficacy assessments in this long-term follow-up study up to 15 years from AVR-RD-01 gene therapy infusion.

Detailed Description
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Participants enrolled in the AVRO-RD-01-201 study will be offered participation in the AVRO-RD-01-LTF01 study. The Baseline visit for the AVRO-RD-01-LTF01 study will coincide with the participant's last visit in the AVRO-RD-01-201 study. Participants confirmed eligible for the AVRO-RD-01-LTF01 study will be asked to return for study visits at approximately 6-month intervals for the first 4 years and annually thereafter for 10 years (for a total of 15 years from AVR-RD-01 infusion) during which time continued safety, engraftment, and efficacy of treatment will be assessed.

Official Title
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A Long-Term Follow-Up Study of Subjects With Fabry Disease Who Previously Received Ex-Vivo, Lentiviral Vector-Mediated Gene-Modified Autologous Cell Therapy AVR-RD-01 in Study AVRO-RD-01-201

Conditions
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Fabry Disease

Intervention / Treatment
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* Other: Safety and Efficacy Assessments


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Subject must have been enrolled and received AVR-RD-01 in the AVRO-RD-01-201 study. Exclusion Criteria: Subject has any medical, psychological, or other condition that, in the opinion of the Investigator: Might interfere with the subject's participation in the study (including consenting to procedures); and/or Poses any additional risk to the subject; and/or Might confound the results of any study-required assessments. Subject is currently enrolled in an AVROBIO-sponsored AVR-RD-01 treatment study.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with Fabry Disease<br>This is a long-term follow-up study of participants who previously received AVR-RD-01 (single dose administration) in the AVRO-RD-01-201 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?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of clinically significant AEs and SAEs |  | 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 vital signs |  | Baseline to Year 15 post gene therapy infusion | 
| Presence of anti-Alpha-galactosidase A (AGA) antibodies |  | Baseline to Year 15 post gene therapy infusion | 
| Presence of replication competent lentivirus (RCL) |  | Baseline to Year 15 post gene therapy infusion | 
| Evaluate for the presence of aberrant clonal expansion as assessed by integration site analysis (ISA) |  | Baseline to Year 15 post gene therapy infusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in AGA enzyme activity level and peripheral blood leukocytes (PBLs) |  | Baseline to Year 15 post gene therapy infusion | 
| Average Vector Copy Number (VCN) in peripheral blood leukocytes 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 Globotriaosylceramide (Gb3) biomarkers for Fabry disease in plasma and urine |  | Baseline to Year 15 post gene therapy infusion | 
| Average Vector Copy Number (VCN) in bone marrow / progenitor cells 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 eGFR |  | Baseline to Year 15 post gene therapy infusion | 
| Change from baseline in left ventricular mass index (LVMI) as assessed by cardiac magnetic resonance imaging (MRI) |  | Baseline to Year 15 post gene therapy infusion | 
| Change from baseline in abdominal pain and stool consistency as assessed by the Diary for Irritable Bowel Syndrome Symptoms-Diarrhea (DIBSS-D) |  | Baseline to Year 15 post gene therapy infusion | 
| Change from baseline in Brief Pain Inventory-Short Form (BPI-SF) questionnaire scores |  | Baseline to Year 15 post gene therapy infusion | 
| Change from baseline in physical and mental functioning as assessed by the Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores |  | Baseline to Year 15 post gene therapy infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fabry Disease, Cell therapy, Gene therapy, Long-term follow-up, Lysosomal storage disorder, Lenti-viral