CAMPSIITE™ RGX-121 Gene Therapy in Subjects With MPS II (Hunter Syndrome)

For males ages 4 months to 5 years

Part 1 Inclusion Criteria:

• The subject's legal guardian(s) is (are) willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
• Is a male ≥4 months to < 5 years of age on Day 1
• Must meet any of the following criteria:
  • Has a documented diagnosis of MPS II and a has a neurocognitive testing score ≤ 77 (Bayley or Kaufman), OR
  • Has a documented diagnosis of MPS II AND has a decline of ≥ 1 standard deviation on serial neurocognitive testing administered between 3 to 36 months apart (Bayley or Kaufman) OR
  • Has a relative clinically diagnosed with severe MPS II who has the same IDS mutation as the subject AND in the opinion of a geneticist has inherited a severe form of MPS II OR
  • Has documented mutation (s) in IDS that in the opinion of a geneticist is always known to result in a neuronopathic phenotype AND in the opinion of a clinician has a severe form of MPS II

Part 2 Inclusion Criteria:

• The subject's legal guardian(s) is (are) willing and able to provide written, signed informed consent after the nature of the study has been explained, and prior to any research-related procedures
• Is a male ≥4 months to < 5 years of age on Day 1
• Has a documented diagnosis of neuronopathic MPS II. Neuronopathic MPS II can be documented with any of the following methods:
  • Has a BSID-III Cognitive Composite score at or below -1 SD (85) from normative mean
  • Has two consecutive neurodevelopmental assessments that support a decline on MSEL visual receptive, expressive language, or fine motor, or BSID-III cognition, expressive language, or fine motor ≥ 1 SD on serial neurocognitive testing administered between 3 to 36 months apart
  • Has a relative clinically diagnosed with neuronopathic MPS II who has the same IDS mutation as the subject AND the subject, in the opinion of a geneticist, has inherited a neuronopathic form of MPS II
  • Has documented mutation(s) in IDS known to result in a neuronopathic phenotype

Part 1 Exclusion Criteria:

• Has contraindications for intracisternal (IC) injection, intracerebroventricular (ICV) injection or lumbar puncture
• Has contraindications for immunosuppressive therapy
• Has neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition
• Has a (cerebral) ventricular shunt that may impact the proper dosing of the subject
• Received hematopoietic stem cell transplantation
• Has had prior treatment with an AAV-based gene therapy product
• Received ELAPRASE® via intrathecal (IT) administration within 4 months of signing the ICF or experienced a serious hypersensitivity reaction to ELAPRASE®
• Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing the ICF, whichever is longer

Part 2 Exclusion Criteria:

• Has a contraindication for an IC injection, ICV injection or lumbar puncture
• Has contraindications for immunosuppressive therapy
• Has neurocognitive deficit not attributable to MPS II or diagnosis of a neuropsychiatric condition
• Has a (cerebral) ventricular shunt that may impact the proper dosing of the subject
• Received hematopoietic stem cell transplantation
• Has had prior treatment with an AAV-based gene therapy product
• Is receiving idursulfase (ELAPRASE®) via intrathecal (IT) administration, or a blood brain barrier-crossing enzyme replacement therapy. Subjects receiving IT ELAPRASE® or a blood brain barrier-crossing ERT may enroll if they agree to discontinue these therapies starting at least 3 months prior to dosing with RGX-121, and for the 24 months of follow-up
• Has received any investigational product within 30 days of Day 1 or 5 half-lives before signing the ICF, whichever is longer