Inclusion Criteria: * Provide written informed consent; * Males and Females ≥18 years of age with late-onset Pompe disease; * Received ERT for at least the previous 24 months * Have clinically moderate, late-onset Pompe disease characteristics; * Agree to use reliable contraception. Exclusion Criteria: * Active hepatitis B and/or C; * Significant underlying liver disease; * Human immunodeficiency virus (HIV) infection; * Prior hypersensitivity to rhGAA; * Pre-existing anti-AAV neutralizing antibody titers; * High titer antibody responses to rhGAA; * Requires any invasive ventilation or requires noninvasive ventilation while awake and upright; * Received any prior vector or gene transfer agent; * Active malignancy (except non-melanoma skin cancer); * History of liver cancer; * Pregnant or nursing women; * Any evidence of active infection at the time of SPK-3006 infusion.