Fabry Disease
Conditions
Keywords
Fabry Disease, Cell therapy, Gene therapy, Long-term follow-up, Lysosomal storage disorder, Lenti-viral
Brief summary
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
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.
Interventions
Safety evaluations, disease-specific assessments, and other assessments to monitor for long-term complications of gene therapy intervention.
Sponsors
AVROBIO
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
MALE
Age
16 Years to 50 Years
Healthy volunteers
No
Inclusion criteria
1\. Subject must have been enrolled and received AVR-RD-01 in the AVRO-RD-01-201 study.
Exclusion criteria
1. 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. 2. Subject is currently enrolled in an AVROBIO-sponsored AVR-RD-01 treatment study.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 AGA enzyme activity level and peripheral blood leukocytes (PBLs) | 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 |
| Change from baseline in Brief Pain Inventory-Short Form (BPI-SF) questionnaire scores | 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 |
Countries
Australia, Brazil
Outcome results
None listed