Long Term Follow-Up for RGX-111

A Long-term Follow-up Study to Evaluate the Safety of RGX-111

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Mucopolysaccharidosis I
• Intervention / Treatment: Genetic: No Intervention

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.

• Study Type: Observational
• Enrollment (Estimated): 21

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre
• United States
  • California
    • Orange, California, United States, 92868
      • Children's Hospital of Orange County

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Received RGX-111 in a separate parent trial.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
RGX-111 Recipients; Subjects who have received RGX-111 in a separate parent study.	Genetic: No Intervention; Observational study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation of the long-term safety of RGX-111	Incidences of treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) over time using CTCAE Version 5.0	5 years inclusive of parent study

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (WASI-II)	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.	5 years inclusive of parent study
Long-term impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (WPPSI-IV)	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.	5 years inclusive of parent study
Long-term impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (BSID-III)	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.	5 years inclusive of parent study
Long-term impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (VABS-III)	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.	5 years inclusive of parent study
Pharmacodynamic Effect of RGX-111 on CSF Biomarkers (HS)	To assess the pharmacodynamic effect of RGX-111 on Heparan Sulfate (HS) levels measures by lumbar puncture.	5 years inclusive of parent study
Pharmacodynamic Effect of RGX-111 on CSF Biomarkers (IDUA)	To assess the pharmacodynamic effect of RGX-111 on α-L-iduronidase (IDUA) levels measures by lumbar puncture.	5 years inclusive of parent study
Pharmacodynamic Effect of RGX-111 on Plasma Biomarkers (HS)	To assess the pharmacodynamic effect of RGX-111 on Heparan Sulfate (HS) levels measures by plasma collection.	5 years inclusive of parent study
Pharmacodynamic Effect of RGX-111 on Plasma Biomarkers (IDUA)	To assess the pharmacodynamic effect of RGX-111 on α-L-iduronidase (IDUA) levels measures by plasma collection.	5 years inclusive of parent study
Pharmacodynamic Effect of RGX-111 on Urine Biomarkers (GAGs)	To assess the pharmacodynamic effect of RGX-111 on glycosaminoglycans (GAGs) levels measured by urine analysis.	5 years inclusive of parent study

Collaborators and Investigators

• Sponsor: REGENXBIO Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 5, 2023
• First Submitted That Met QC Criteria: October 25, 2023
• First Posted (Actual): October 26, 2023

Study Record Updates

• Last Update Posted (Actual): April 29, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Gene Therapy; MPS I; Hurler Syndrome
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Connective Tissue Diseases; Carbohydrate Metabolism, Inborn Errors; Lysosomal Storage Diseases; Mucinoses; Mucopolysaccharidoses; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Skin and Connective Tissue Diseases; Mucopolysaccharidosis I
• Other Study ID Numbers: RGX-111-5101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No