Inclusion Criteria: * Male or female 5 years to 65 years of age. * Clinical diagnosis of MPS II (based on evidence of hepatosplenomegaly, dysostosis multiplex by X-ray, valvular heart disease, or obstructive airway disease) IDS deficiency confirmed by gene sequencing. Exclusion Criteria: * Known to be unresponsive to ERT * Neutralizing antibodies to AAV 2/6 * Serious intercurrent illness or clinically significant organic disease (unless secondary to MPS II) * Receiving antiviral therapy for hepatitis B or C, or with active hepatitis B or hepatitis C or HIV 1/2 * Lack of tolerance to idursulfase treatment with significant IARs or occurrence of anaphylaxis * Markers of hepatic dysfunction * Creatinine ≥ 1.5 mg/dL * Contraindication to the use of corticosteroids for immunosuppression * Current treatment with systemic (IV or oral) immunomodulatory agent or steroid use (topical treatment allowed) * Participation in prior investigational drug or medical device study within the previous 3 months * Prior treatment with a gene therapy product * Elevated or abnormal circulating α-fetoprotein (AFP) * Weight \< 20 kg at Screening Visit