A Phase III Study of JR-141 in Patients With Mucopolysaccharidosis II (STARLIGHT)

Inclusion Criteria:

• A patient who voluntarily signs an Institutional Review Board or Independent EthicsCommittee-approved written informed consent form. If the patient is aged under 18years (aged under 16 years in the UK) at the time of enrollment or willingness toparticipate in the study cannot be confirmed due to MPS II-related intellectualdisability, the patient's legally acceptable representative (e.g., his/her parentsor guardians) may sign the informed consent on behalf of the patient. Writteninformed assent should be obtained from the patient, wherever possible.

• Patients with confirmed diagnosis of MPS II

• Naïve patients or patients who are receiving stable enzyme replacement therapy withidursulfase for more than 12 weeks before starting administration of JR-141 oridursulfase for this study.

• Patients or patients whose partners are of child-bearing potential agree to use amedically accepted, highly effective method of contraception being use of condomsfrom the time of informed consent.

<Cohort A>

• Patients aged 36-42 months old at the time of ICF signing: patients must have astandard score measured by the BSID-III of 85 or less at screening.

• Patients aged 43-71 months old at the time of ICF signing: patients must EITHER have (1) A DQ measured by BSID-III of 20 to 85 at screening OR (2) A composite standardscore on NVI measured by KABC-II of 85 or less at screening (only who can performKABC-II)

• Patients aged 30-35 months old at the time of randomization and who are judged ashaving the severe phenotype by the Expert Board.

<Cohort B>

• Patients 6 years of age or older at the time of ICF signing and whose IQ are 70 andhigher.

• Enrollment of subjects in Cohort B is contingent on the availability in that countryof a validated country-specific version of the test (either WISC-V, WAIS-IV, orT.O.V.A.).

• Attenuated patients with 1 SD deficiency in the omission errors or variabilitydomains of the T.O.V.A..

Exclusion Criteria:

• A patient with a history of HSCT with successful engraftment.

• A patient who has received gene therapy treatment at any point.

• Unable to undergo lumbar puncture.

• A patient who is enrolled in another clinical study that involves clinicalinvestigations or use of any investigational product (drug or device) within 4months before obtaining informed consent.

• Unable to comply with the protocol as determined by the principal investigator orsubinvestigator.

• Judged by the principal investigator or subinvestigator to be ineligible toparticipate in the study due to a history of serious drug allergy or sensitivityincluding anesthesia or hypersensitivity to any component of JR-141.

• A patient who has a known or suspected local or general infection or is at risk ofabnormal bleeding due to medical conditions or therapies.

• A patient who has documented mutation of other genes, including loci adjacent to theIDS gene that are known to be associated with developmental delay, seizures, orother significant CNS disorders.

• A patient who has documented loss of activity of sulfatases other than IDS.

• A patient who has had a ventriculoperitoneal shunt placed or any other brainsurgery, or has a clinically significant ventriculoperitoneal shunt malfunctionwithin 30 days of screening.

• full time employee of the sponsor or research site personnel directly affiliatedwith this study or their immediate family members.

• A patient who otherwise is judged by the principle investigator or sub-investigatorto be ineligible to participate in the study.

[Only in France]

• Persons deprived of their liberty by a judicial or administrative decision,according to article L.1121-6 the Public Health Code (Code de la santé publique),adults who are the subject of a measure of legal protection or unable to expresstheir consent according to article L. 1121-8 of the Code de la santé publique)