Gene Transfer Study in Patients With Late Onset Pompe Disease

Inclusion Criteria: * Participant is aged ≥ 18 years. * Participant has a documented clinical diagnosis of Pompe disease by genetic testing. * Participant has received enzyme replacement therapy (ERT) with rhGAA for the previous ≥ 2 years. * Participant has been on a stable standard dose (at least 20 mg/kg every 2 weeks) of ERT with rhGAA for at least the previous 6 months. * Participant or legally authorized representative(s) (LAR) (if applicable) provides written informed consent. * Participant and LAR(s) are willing and able to comply with study visits and study procedures. * Participant must agree to refrain from blood or blood products donation and sperm or egg donation from the time of AT845 administration until the later of 90 days or 3 consecutive negative viral shedding samples * Participants enrolled in previous protocol versions 1 through 9: Participant has upright FVC ≥ 30% of predicted normal value. Participants enrolled starting with protocol version 10 and subsequent amendments: Participant has upright FVC ≥ 30% and ≤ 85% of predicted normal value. * Participants enrolled starting with protocol version 10 and subsequent amendments: Participant who is able to ambulate ≥ 40 m without stopping and without the use of an assistive device. The use of an assistive device for community ambulation is acceptable. (Participants enrolled under previous protocol versions 1 through 9 will not be excluded if they do not meet this criterion during Rescreening visit). Exclusion Criteria: * Participant is currently participating in an interventional study or has received gene or cell therapy. * Participant tests positive for AAV8 antibodies with titers \>1:20 neutralizing. * Participant has received immune-modulating agents within 90 days before dosing (use of inhaled corticosteroids is allowed); use of other concomitant medications to manage chronic conditions must have been stable for at least 30 days before dosing. Concomitant medications that may predispose the participant to peripheral neuropathy will be evaluated. * Participant has any clinically significant laboratory values (other than those directly associated with LOPD \[e.g., GAA, serum creatine kinase (CK)\]) that would preclude participation in the study. * Participant has serological or viral load evidence of HIV-1 or HIV-2. * Participant has received drugs for treatment of myopathy or neuropathy with immunosuppressive therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, IV immunoglobulin, rituximab) within 3 months prior to starting the study * Participant has a high risk for a severe allergic reaction to rhGAA (ie, previous moderate to severe anaphylactic reaction to alglucosidase alfa or and/or a history of sustained high immunoglobulin G \[IgG\] antibody titers to alglucosidase alfa that suggests a high risk for an allergic reaction to ERT). * Participant has a history of hypersensitivity to β2 agonist drugs such as albuterol, levalbuterol, bitolterol, pirbuterol, terbutaline, salmeterol, which contraindicates pulmonary function testing. * Participant has an active viral infection based on clinical observation. * Participant has a history of or concurrent medical condition other than Pompe disease that could jeopardize safety of the participant or impact study results. * Participant has a history of, or currently has, a clinically important cardiac condition, such as an echocardiogram (ECHO) with ejection fraction below 40% or has symptoms or signs of cardiomyopathy that precludes enrollment. * Participant has a contraindication to study drug or to corticosteroids, or has demonstrated hypersensitivity to any of the components of the study drug. * Participant tests positive for GAA antibodies with titers \> 1:50,000 total * Participant has a history of hypersensitivity to MRI contrast agents including gadolinium. * Participant has a known hypersensitivity to local anesthetics such as lidocaine. * Participant has a bleeding diathesis, e.g., due to anti-coagulation or anti-platelet treatments. * Participant has a concurrent medical condition (including uncontrolled diabetes, alcohol use disorder, certain autoimmune conditions, Lyme disease, active malignancy requiring chemotherapy and/or radiation, uremic nephropathy, known exposure to heavy metals) commonly associated with peripheral neuropathy. Other concurrent medical conditions that may predispose to peripheral neuropathy will be evaluated and action taken on a case-by-case basis, following discussion between the Investigator and Medical Monitor. * Participant who is unwilling to withdraw from ERT. * Participant has an active symptomatic large fiber peripheral neuropathy diagnosed by a neurologist at a screening visit. * Age-related sensory changes on NCS without symptoms or mononeuropathy (refers to focal involvement of a single nerve, usually due to a local cause such as trauma, compression or entrapment) will not be excluded. * Participant has clinically significant underlying liver disease at Screening, or has any of the following: * Alanine Aminotransferase (ALT) \> 2 × upper limit of normal (ULN) * Aspartate aminotransferase (AST) \> 2 × ULN * Total bilirubin \> 1.5 × ULN * Alkaline phosphatase (ALP) \> 2 × ULN * ALT and AST are often higher than the normal range in Pompe disease patients. Participants whose liver laboratory tests fall outside the above ranges may be retested and, if the eligibility criteria are met on retesting, may be enrolled after confirmation by the Medical Monitor. * In addition, participants with abnormal laboratory results related to confirmed benign liver conditions including Gilbert's syndrome (defined by asymptomatic unconjugated hyperbilirubinemia \[17 to 70 µmol/L or 1 to 4 mg/dL\]) and asymptomatic gallstones, will be considered eligible for the study notwithstanding their abnormal laboratory results and may be enrolled. * Participant is currently on antiviral therapy for hepatitis B or C, or chronic/active hepatitis B or active hepatitis C evidenced by hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), hepatitis B virus (HBV)-DNA positivity or hepatitis C virus (HCV)-RNA viral load positivity, respectively. * Negative viral load assays in 2 samples, collected at least 6 months apart, will be required to be considered negative. Both natural clearers and those who have cleared HCV on antiviral therapy are eligible. Participant has an active viral infection based on clinical observation.