Mucopolysaccharidosis I
Conditions
Keywords
MPS I, Hurler Syndrome, Gene Therapy
Brief summary
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
This is a prospective, multicenter, long-term 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 intracisternal (IC) or intraventricular (IVR; also referred to as intracerebroventricular \[ICV\]) infusion 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). No treatment will be directed under this observational study. 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.
Interventions
GENETICNo Intervention
Observational study
Sponsors
REGENXBIO Inc.
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of the long-term safety of RGX-111 | 5 years inclusive of parent study | Incidences of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) over time using CTCAE Version 5.0 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Long-term impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (WASI-II) | 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 in individuals from ages 6 to 90 years old. The assessment will yield composite scores that estimate verbal comprehension and perceptual reasoning abilities. The age equivalent scores are also provided for each of the subtests. |
| Long-term impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (WPPSI-IV) | 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 the cognitive development in young children approximately 30 to 91 months in age. This study utilizes the General Ability Index (GAI) comprised of 4 core subtests depending on the child's age; the subtests include receptive vocabulary, block design, information, and quiet assembly for children 3 to 47 months and block design, information, matrix reasoning and similarities for ages 48 to 91 months. The subtests have different scoring ranges, with higher subtest raw scores indicating completion of more complex items but can be normalized from cross-subtest comparison. |
| Long-term impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (BSID-III) | 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. The BSID-III assesses children aged 1 to 42 months across several domains to give a holistic view of the child's development and potential delays. Participants will be assessed for the Cognitive, Language and Motor domains of the BSID-III. The domains have different scoring ranges but can be normalized for cross-domain comparisons. |
| Long-term impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (VABS-III) | 5 years inclusive of parent study | Change from 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 comparisons. |
| Pharmacodynamic Effect of RGX-111 on CSF Biomarkers (HS) | 5 years inclusive of parent study | To assess the pharmacodynamic effect of RGX-111 on Heparan Sulfate (HS) levels measures by lumbar puncture. |
| Pharmacodynamic Effect of RGX-111 on CSF Biomarkers (IDUA) | 5 years inclusive of parent study | To assess the pharmacodynamic effect of RGX-111 on α-L-iduronidase (IDUA) levels measures by lumbar puncture. |
| Pharmacodynamic Effect of RGX-111 on Plasma Biomarkers (HS) | 5 years inclusive of parent study | To assess the pharmacodynamic effect of RGX-111 on Heparan Sulfate (HS) levels measures by plasma collection. |
| Pharmacodynamic Effect of RGX-111 on Plasma Biomarkers (IDUA) | 5 years inclusive of parent study | To assess the pharmacodynamic effect of RGX-111 on α-L-iduronidase (IDUA) levels measures by plasma collection. |
| Pharmacodynamic Effect of RGX-111 on Urine Biomarkers (GAGs) | 5 years inclusive of parent study | To assess the pharmacodynamic effect of RGX-111 on glycosaminoglycans (GAGs) levels measured by urine analysis. |
Countries
Brazil, United States
Outcome results
None listed