Study to determine the effectiveness and safety of DNL310 vs idursulfase in pediatric participants with neuronopathic or non-neuronopathic Hunter Syndrome

INTERVENTION: Study interventions: 1. Dose of DNL310: 15 mg/kg dosed once per week as an IV infusion. 2. Idursulfase: recommended dose (0.5 mg/kg) once per week as an IV infusion. Study cohorts and trial arm details: Cohort A: Approximately 33 participants aged =2 to <6 years with nMPS II, as determined based on genetic testing (and cognitive testing or family history, as applicable), will be randomized 2:1 to receive either DNL310 or IV idursulfase until Week 96. Target enrollment is for at least 70% of the participants to be aged =24 and =48 months at randomization. Randomization will be stratified by chronological age (=48 months or > 48 months) and genotype (presence or absence of a known severe IDS variant [eg, whole‐gene deletion or large rearrangement]). Cohort B: Approximately 21 participants aged =6 to <17 years with nnMPS II, as determined based on genetic and cognitive testing, will be randomized 2:1 to receive either DNL310 or IV idursulfase until Week 48. Randomization will be stratified by chronological age (<12 years or =12 years). Dose of DNL310: 15 mg/kg dosed once per week as an IV infusion. Dose of idursulfase: recommended dose (0.5 mg/kg) once per week as an IV infusion. CONDITION: Mucopolysaccharidosis Type II [MPS II] ; Nutritional, Metabolic, Endocrine ; Mucopolysaccharidosis, type II PRIMARY OUTCOME: 1. Cerebrospinal fluid (CSF) heparan sulfate (HS) concentration is measured via CSF samples taken at baseline and Week 24 (Cohort A only); 2. Adaptive behaviour is assessed by the Vineland‐3 scale at baseline and Week 96 (Cohort A only) SECONDARY OUTCOME: 1. Neurocognitive development is assessed by the Bayley Scales of Infant and Toddler Development, Third Edition (BSID‐III) at baseline and Week 96 (Cohort A only); 2. Physical endurance is measured as distance walked in the 6 Minute Walk Test (6MWT) at baseline and Week 48 (Cohort B only); 3. Onset and durability of peripheral efficacy are measured by the sum of urine heparan sulfate (HS) and dermatan sulfate (DS) concentrations at baseline and Week 48 (Cohorts A and B); 4. Liver volume within the normal range (normal vs abnormal) as measured by MRI at Week 48 (Cohorts A and B); 5. Spleen volume within the normal range (normal vs abnormal) as measured by MRI at Week 48 (Cohorts A and B); 6. Parents’/caregivers’ assessment of efficacy is measured by improvement in the Parent/Caregiver Global Impression Assessment (CaGI‐C) Overall MPS II at Week 48 (Cohorts A and B) INCLUSION CRITERIA: 1. Participants aged =2 to <6 years (Cohort A) or =6 to <17 years (Cohort B) 2. Confirmed diagnosis of MPS II (for Cohort A, nMPS II; for Cohort B, nnMPS II) 3. Be on maintenance enzyme replacement therapy (ERT) and have tolerated idursulfase for a minimum of 4 months prior to screening