A Fabry Disease Gene Therapy Study

Inclusion Criteria: 1. Adult males, ≥ 18 years of age with classic Fabry disease. 2. Confirmed diagnosis of classic Fabry Disease 3. Decreased plasma alpha galactosidase (αGLA) activity at screening. 4. One or more of the characteristic features of classic Fabry disease. 5. Estimated glomerular filtration rate (eGFR) ≥60mL/min/1.73m2 at screening. 6. \<500 mg/g Urine Protein to Creatinine Ratio (UPCR) in a spot urine sample OR \< 1g/24 hours of urinary protein (24hour urine analysis), at 7. Able to give full informed consent and able to comply with all requirements of the trial including the 5-year long term follow-up. 8. Willingness to practice barrier contraception whilst vector shedding via semen is present. 9. Lack of AAV neutralizing antibodies within 6 weeks prior to dosing. 10. For inclusion in Part 1, subjects must have received either a licensed ERT or PCT for at least 12 months prior to dosing. For inclusion in Part 2, subjects must never have been previously dosed with Enzyme Replacement Therapy (ER) or Pharmacological Chaperone Therapy (PCT). 11. Willingness to avoid strenuous exercise during first 3 months after dosing. Exclusion Criteria: 1. Non-classical Fabry disease. 2. Prior hypersensitivity or intolerance to ERT 3. Prior lack of response to ERT. 4. Subjects with a history of chronic kidney disease for a minimum of 3 months. 5. Subjects with severe myocardial fibrosis. 6. Use of investigational therapy for Fabry disease within 60 days before enrolment. In addition, participation in any other clinical trial of an investigational medicinal product (IMP), and/or receiving any other IMP during the course of the study 7. Evidence of liver dysfunction as demonstrated by elevated blood levels during screening. 8. Platelet count \< 100 xE9L. 9. Subjects receiving warfarin or other anticoagulants or subjects with a clinically significant bleeding disorder. 10 - 12. Either history of, or a positive serology test at screening for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis C antibody (HCAb) and human immunodeficiency virus (HIV) or a negative test at screening for anti-varicella zoster virus (VZV) IgG or hepatitis surface antibody (HBsAb). 13\. Subjects with a history of or a positive screening test for tuberculosis. 14. Subjects who have received a live attenuated vaccination within 12 weeks prior to screening or intend to receive such a vaccine within the course of the study. 15\. Uncontrolled glaucoma, diabetes mellitus, or hypertension. 16. History of any malignancy requiring treatment. 17. History or detection of significant arrhythmia during screening. 18. Subjects with uncontrolled cardiac failure, unstable chest pain, or heart attack deemed significant in the past 6 months. 19\. History of acute myocarditis or presence of acute myocarditis during screening. 20\. Prior treatment with any gene therapy medicinal product. 21. Known or suspected intolerance to gadolinium, tacrolimus and other macrolides, steroids, local anesthetics used for skin or renal biopsies, or any non-investigational medicinal products (NIMPs) or their excipients. 22\. Subjects with contraindications to MRI. Including subjects with ferromagnetic metallic implants, including pacing and defibrillator devices, nerve stimulators and cochlear implants. 23\. Subjects who have had a renal transplant. 24. Cytomegalovirus immunoglobulin positive subjects who are CMV polymerase chain reaction (PCR) positive at screening. 25-26.History of physical or psychiatric illness that could affect the subject's ability to participate or a history of substance abuse including alcohol abuse.