Title
Open Label, Study Of Efficacy and Safety Of AVR-RD-01 for Treatment-Naive Subjects With Classic Fabry Disease
An Open-Label, Multinational Study Of The Efficacy And Safety of Ex Vivo, Lentiviral Vector-Mediated Gene Therapy AVR-RD-01 For Treatment-Naive Subjects With Classic Fabry Disease
Phase
Phase 1/Phase 2Lead Sponsor
AvroBioStudy Type
InterventionalStatus
TerminatedIndication/Condition
Fabry DiseaseIntervention/Treatment
AVR-RD-01Study Participants
11This is a multinational, open-label study to assess the efficacy and safety of AVR-RD-01 in approximately 8 to 12 male subjects 16 years of age or older and postpubertal with a confirmed diagnosis of classic Fabry disease based on deficient AGA enzyme activity who have not previously received treatment with enzyme replacement therapy (ERT) and/or chaperone therapy within 3 years of the time of Screening.
The duration of each subject's participation in this study will be approximately 64 weeks (or 1 year, 12 weeks), comprised of a five study periods (Screening, Baseline, Pre-transplant, Transplant, and Post-transplant Follow-up). During the Screening Period (approximately 8 weeks), written informed consent (and assent, if applicable) will be obtained and the subject will complete other Screening procedures to confirm study eligibility. Once study eligibility is confirmed, subjects will enter the Baseline Period (up to 3 days) during which time assessments will be performed to establish a pre-transplant baseline. Once baseline assessments are complete, the subject will enter the Pre-transplant Period (approximately 6 weeks) during which time mobilization, apheresis, AVR-RD-01 drug product preparation and testing for release, and conditioning regimen administration to achieve myeloablation will take place. Following completion of the Pre-transplant Period, the subject will enter the Transplant Period (1 day) during which time AVR-RD-01 infusion will take place. After AVR-RD-01 infusion, the subject will enter the Post-transplant Follow-up Period (approximately 48 weeks), during which time periodic safety and efficacy assessments will be performed to assess measures of engraftment, clinical response, and safety post-transplant.
After study completion, consenting subjects will continue periodic safety and efficacy assessments for approximately 14 years (for a total of 15 years post-transplant follow-up) in a long-term follow-up study to AVRO-RD-01-201.
The subject will receive a one-time IV infusion of AVR-RD-01.
AVR-RD-01 Drug Product (autologous CD34+ cell-enriched fraction that contains cells transduced with Lentiviral Vector/alpha-galactosidase A (AGA) encoding for the human AGA complementary deoxyribonucleic acid (cDNA) sequence
Inclusion Criteria: Subject is male, 16 years of age or older (18 years of age or older in the US), and postpubertal,(minimum age by region) Subject has a confirmed diagnosis of classic Fabry disease based on deficient AGA enzyme activity (defined as < 1% of normal). Exclusion Criteria: Subject has a GLA gene mutation associated with late-onset cardiac variant Fabry disease. Subject has previously received ERT and/or chaperone therapy within 3 years for treatment of Fabry disease. Subject has tested positive for anti-AGA antibodies at the time of screening. Subject has eGFR < 60 mL/min/1.73 m² (ie, chronic kidney disease [CKD] stage ≥ 3) at Screening. Subject has a prior history of myocardial infarction (MI). Subject has a history of coronary artery disease (CAD) with angina requiring percutaneous transluminal coronary angioplasty (with or without stent placement) and/or coronary artery bypass graft (CABG). Subject has a history of moderate to severe valvular heart disease requiring valve replacement. Subject has a history of heart failure, moderate to severe diastolic dysfunction, and/or left ventricular ejection fraction (LVEF) ≤ 45% on echocardiogram (ECHO) performed at rest at Screening. Subject has a history of clinically significant cardiac arrhythmia (eg, heart block [second or third degree], atrial fibrillation requiring therapy, ventricular fibrillation, ventricular tachycardia, supraventricular tachycardia, or cardiac arrest). Note [history of intermittent atrial fibrillation not requiring treatment is allowed]. Subject has a prior history of stroke and/or transient ischemic attack (TIA). Subject has aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal (ULN) at Screening. Subject has a prior history of (or current) malignancy; the one exception is a prior history of resected basal cell carcinoma. Subject has previously received treatment with AVR-RD-01 or any other gene therapy. Other inclusion/exclusion criteria apply.
