Long Term Follow-Up for RGX-111

Study Overview
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Brief Summary
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RGX-111-5101 is a long-term follow up study that evaluates the long term safety and efficacy of RGX-111 in participants who have received RGX-111 (a gene therapy intended to deliver a functional copy of the alpha-L-iduronidase gene (IDUA) to the central nervous system) in a separate parent study.

Detailed Description
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This is a prospective, multicenter, observational, follow-up study to evaluate the long-term safety and efficacy of RGX-111 after a single administration. Eligible participants are those who previously participated in a clinical study where they received a single IC or ICV administration of RGX-111. Enrollment of each participant in this study should occur on the same day or after the participant has completed the end of study (EOS) visit or early discontinuation visit (EDV) from a previous (parent) clinical study. Participants will be followed for up to five years after RGX-111 administration (inclusive of the parent study) or until RGX-111 is commercially available in the participant's country, whichever occurs first. No treatment will be directed under this observational protocol. The total study duration for each participant may vary depending on when s/he enrolls in the current study following RGX-111 administration in the parent study.

Official Title
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A Long-term Follow-up Study to Evaluate the Safety and Efficacy of RGX-111

Conditions
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Mucopolysaccharidosis I

Intervention / Treatment
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* Genetic: No Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: To be eligible, a participant must have previously received RGX-111 in a separate parent trial. Participant or participant's legal guardian(s) is/(are) willing and able to provide written, signed informed consent. Exclusion Criteria: None.
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| RGX-111 Recipients<br>Subjects who have received RGX-111 in a separate parent study. | Genetic: No Intervention<br>* Observational study<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the long-term safety of RGX-111 | Incidences of treatment-emergent adverse events (TEAE) and serious adverse events (SAEs) over time | 5 years inclusive of parent study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarkers | Change from baseline in Glycosaminoglycan levels (ng/mL) | 5 years inclusive of parent study | 
| Biomarkers | Change from baseline in measurement of biomarkers in cerebrospinal fluid (CSF). | 5 years inclusive of parent study | 
| Biomarkers | Change from baseline in measurement of biomarkers in plasma. | 5 years inclusive of parent study | 
| Biomarkers | Change from baseline in measurement of biomarkers in urine. | 5 years inclusive of parent study | 
| Change from baseline in neurodevelopmental parameters | as measured by the Bayley Scales of Infant and Toddler Development Third Edition (BSID-III). The BSID-III assesses children with developmental functioning ranging from 1-42 months. In this study, participants will be assessed for the Cognitive, Language, and Motor domains. The domains have different scoring ranges, with higher subtest raw scores indicating better function, but can be normalized for cross-domain comparison. | 5 years inclusive of parent study | 
| Change from baseline in neurodevelopmental parameters | Change in baseline adaptive behavior as measured by Vineland Adaptive Behavior Scales Third Edition (VABS-III). The VABS-III assesses adaptive behavior in individuals from infancy to age 90 years. In this study, 4 domains of Communication, Daily Living Skills, Socialization, and Motor Skills will be assessed. The domains have different scoring ranges, with higher subdomain raw scores indicating greater function, but can be normalized for cross-domain comparison. | 5 years inclusive of parent study | 
| Change from baseline in neurodevelopmental parameters | As measured by the Wechsler Abbreviated Scale of Intelligence (WASI-II). The WASI-II assesses intelligence for individuals from ages 6 to 90 years old. The assessment yields composite scores that estimates verbal comprehension and perceptual reasoning abilities. The subtests have different scoring ranges, with higher subtest raw scores indicating completion of more complex items, but can be normalized for cross-subtest comparison. | 5 years inclusive of parent study | 
| Change from baseline in neurodevelopmental parameters | As measured by the Wechsler Preschool and Primary Scale of Intelligence Fourth Edition (WPPSI-IV). The WPPSI-IV measures cognitive development in young children from ages 30-91 months of age. This study utilizes the General Ability Index (GAI) comprised of 4 core subtests depending on the child's age. The subtests have different scoring ranges, with higher subtest raw scores indicating completion of more complex items, but can be normalized for cross-subtest comparison. | 5 years inclusive of parent study | 
| Change from baseline in neurodevelopmental parameters | As measured by the Tests of Variables of Attention (TOVA) | 5 years inclusive of parent study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MPS I, hurler syndrome, gene therapy