Key Inclusion Criteria:
* Male of age ≥ 18 years and ≤50 years
* Confirmed clinical diagnosis of classic Fabry disease (FD) defined as:
1. Absent or minimal αGAL A enzyme activity \< 1% of mean normal measured in plasma regardless of variant status; OR
2. α-galactosidase A (GLA) pathogenic or likely pathogenic variant associated with classic FD phenotype identified on molecular genetic testing with plasma αGLA A enzyme activity below lower bound of the reference range (as measured at trough enzyme replacement therapy \[ERT\] levels).
* eGFR ≥ 40 mL/min/1.73 m2
* Suboptimal response after at least 12 months of enzyme replacement therapy (ERT) treatment. Suboptimal response is defined as plasma lyso-Gb3 ≥ 2.3 nanograms per milliliter (ng/mL) at Screening and one or both of the following:
* Persistent moderate or severe neuropathic pain (intermittent or continuous) over a period of at least 3 months prior to consent
* Presence of gastrointestinal symptoms (abdominal cramping, constipation, or diarrhea), reported by the Participant as moderate or severe and that are either persistent or occurring two or more times over the 12 weeks prior to consent
* Weight ≤ 120 kilograms (kg)
Key Exclusion Criteria:
* Any allergic hypersensitivity reaction to ERT or infusion reaction in the 12 months prior to consent that was of severity grade 3 or above based on Common Terminology Criteria for Adverse Events (CTCAE v5.0) and required emergency intervention for hypertension/hypotension to stabilize blood pressure or hypoxia OR any other life-threatening complication.
* Proteinuria, with random urine protein/creatinine ratio (rUPCR) ≥1 mg/mg at Screening
* Current use of chaperone therapy such as migalastat (Galafold®)
* Malignancy within 5 years of Screening, except for basal or squamous cell carcinoma of the skin
* Presence of chronic, active, or latent infection with hepatitis B or C, human immunodeficiency virus (HIV), or tuberculosis (TB) as assessed at the screening visit
* Active or ongoing infection or any other significant concurrent, uncontrolled medical condition including, but not limited to, renal, hepatic, cardiovascular, hematological, GI, endocrine (such as diabetes mellitus with poor glycemic control), pulmonary, neurological, cerebral, or psychiatric disease, alcoholism, drug dependency, or any other psychological disorder that could, in the opinion of the Investigator, risk the safety of the Participant, or interfere with adherence to the protocol procedures or interpretation of results
* Evidence of any liver disease, including hepatitis, fibrosis, cirrhosis of the liver, neoplastic lesion, or any known medical condition that could impact the intended transduction of the vector and/or expression and activity of the protein
* History of kidney transplantation or currently on hemodialysis or peritoneal dialysis
* Uncontrolled hypertension, defined as systolic blood pressure \>140 millimeters of mercury (mmHg) (inclusive) and/or diastolic blood pressure outside the range of 60 to 85 mmHg (inclusive) at Screening, confirmed on at least 2 repeated measurements
* Patients taking blood pressure medication to control blood pressure or proteinuria (eg, angiotensin-converting enzyme \[ACE\] inhibitors and angiotensin II receptor blockers \[ARBs\]) and have been titrated to a stable dose for at least 3 months prior to Screening are allowed in the study.
* Glycated hemoglobin (HbA1c) at Screening ≥7%
* Contraindication to systemic corticosteroid therapy or immunosuppressive therapy
* Chronic steroid use, defined as ≥ 3 months of oral corticosteroid use within the 12 months prior to Screening
* Screening laboratory values for renal and liver function that meet or exceed any of the following:
1. Alanine transaminase (ALT) \> 2 x upper limit of normal for the testing laboratory (ULN)
2. Aspartate aminotransferase (AST) \> 2 x ULN
3. Total Bilirubin \> 2 x ULN (except if this is caused by Gilbert disease)
4. Alkaline phosphatase (ALP) \> 2 x ULN
5. Creatinine \> 2 x ULN
* Screening laboratory values for hematologic and coagulation function that meet any of the following:
1. Hemoglobin \< lower limit of normal (LLN) (as per reference laboratory ranges)
2. Platelet count \< 150 x1000/μl
3. International normalized ratio (INR) \>1.1
4. Soluble terminal complement complex (sC5b-9)\>ULN
* Significant anatomical abnormalities on renal ultrasound such as the presence of only 1 kidney, significant differences in kidney sizes between the right and left kidneys \>1.5 centimeters (about 0.59 inch), or presence of kidney cysts
