Type 1 Gaucher Disease
Conditions
Keywords
Gaucher, Guard1
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.
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
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with clinically relevant abnormalities, as assessed by electrocardiograms (ECGs) | 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 |
| Change from baseline over time in spleen volume as assessed by abdominal Magnetic Resonance Imaging (MRI) | Baseline to Year 15 post gene therapy infusion |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Change from baseline over time in glucocerebrosidase (GCase) GCase enzyme activity level in | Baseline to Year 15 post gene therapy infusion |
Countries
Canada, United States
Outcome results
None listed