RGX-111 Gene Therapy in Patients With MPS I

NCT03580083 | Suspended Phase 1 DMC FDA Drug

• 1 other identifier: RGX-111-002
• Study Type: interventional
• Target: 21
• Locations: 2 countries
• Sites: 2

Brief Summary

RGX-111 is a gene therapy which is intended to deliver a functional copy of the α-L-iduronidase (IDUA) gene to the central nervous system. This is a safety and dose ranging study to determine whether RGX-111 is safe and tolerated by patients with MPS I.

Conditions

Mucopolysaccharidosis Type I (MPS I); Hurler Syndrome; Hurler-Scheie Syndrome

Keywords

MPS I , gene therapy, Hurler, Hurler- Scheie

Outcome Measures

Primary Outcomes (1)

• Safety and Tolerability

  Number of participants with treatment-related adverse events and serious adverse events. To evaluate safety and tolerability following a single IC or IVR dose administered to participants who have documented CNS involvement due to MPS I.

  24 Weeks

Secondary Outcomes (12)

• Long-term Safety and Tolerability

  104 Weeks

• Evaluation of the impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (WASI-II)

  104 Weeks

• Evaluation of the impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (BSID-II)

  104 Weeks

• Evaluation of the impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (WPPSI-IV)

  104 Weeks

• Evaluation of the long-term impact of RGX-111 on neurodevelopmental parameters of cognitive, behavioral, and adaptive function (VABS-III)

  104 Weeks

Study Arms (2)

Dose 1; 1x10^10 GC/g brain mass of RGX-111

EXPERIMENTAL

Genetic: RGX-111

Dose 2; 5x10^10 GC/g brain mass of RGX-111

EXPERIMENTAL

Genetic: RGX-111

Interventions

RGX-111 GENETIC

Recombinant adeno-associated virus serotype 9 capsid containing α-L-iduronidase expression cassette

Dose 1; 1x10^10 GC/g brain mass of RGX-111; Dose 2; 5x10^10 GC/g brain mass of RGX-111

Eligibility Criteria

• Age: 4 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• A male or female ≥ 4 months of age.
• Willing and able to provide written, signed informed consent after the nature of the study has been explained and prior to any study-related procedures. If the participant is unable to provide informed consent, then informed assent will be obtained, and informed consent must be provided by the participant's legal guardian.
• Having previously documented diagnosis of MPS I confirmed by molecular genetic testing, or IDUA deficiency in leucocytes or fibroblasts.
• Has documented evidence of CNS involvement due to MPS I based on one of the following criteria, if not explainable by any other neurologic or psychiatric factors:
• A score of ≥ 1 standard deviation below mean on neurodevelopmental testing or in 1 domain of neuropsychological function.
• A decline of \> 1 standard deviation on sequential neurodevelopmental testing or in 1 domain of neuropsychological function administered between 3 to 36 months apart.
• Has a documented diagnosis of severe MPS I confirmed by biallelic mutations predictive of the severe phenotype or has a relative clinically diagnosed with severe MPS I and the same IDUA mutations. This participant is not required to have documented evidence of neurocognitive deficit.
• Participants who have had HSCT may be enrolled in the study if the investigator, Medical Monitor, and Sponsor agree that he/she can safely and successfully participate in the study.
• Has sufficient auditory and visual capacity, with or without aids, to complete the required protocol testing and willing to be compliant with wearing the aid, if applicable, on testing days.
• Females of childbearing potential must have negative serum pregnancy test at the screening visit, have negative results on Day 1, and be willing to have additional pregnancy tests during the study.
• Sexually active male participants must be willing to use a medically accepted method of barrier contraception (eg, condom or female diaphragm) from the screening visit until 24 weeks after vector administration. Cessation of birth control after this point should be discussed with the participant's physician.
• Sexually active females must be willing to use an effective method of birth control from the screening visit until 12 weeks after the last dose of sirolimus or tacrolimus, whichever is later. Cessation of birth control after this point should be discussed with the participant's physician. Effective methods of birth control include a double barrier method (eg, male condom plus a diaphragm), an intrauterine device, or hormonal contraception. Sustained abstinence is an acceptable practice; however, periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception.

You may not qualify if:

• Has any contradiction to MRI, contrast or to general anesthesia
• Has any contradiction to gadolinium
• Has renal insufficiency as determined by an estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2, based on creatinine. If the laboratory determines that the creatinine level is less than the lower limit of assay validation or detection, then the lowest limit cutoff value will be used for the eGFR.
• Has a contradiction for an IC and IVR infusion, including any of the following:
• Review of baseline MRI testing by the team of neuroradiologists/neurosurgeons participating in the study (1 per site) shows a contraindication for an IC and an IVR infusion.
• History of prior head/neck surgery, which resulted in a contraindication to IC and IVR infusion, based on review of available information by the team of neuroradiologists/neurosurgeons participating in the study.
• Has previously experienced a clinically significant intracranial bleed that, in the opinion of the investigator and team of neuroradiologists/neurosurgeons, is a contraindication to IC and IVR infusion.
• Has any neurocognitive deficit not attributable to MPS I or has a diagnosis of a neuropsychiatric condition that may, in the opinion of the investigator, confound interpretation of study results.
• Has any contradiction to lumbar puncture.
• Has received IT laronidase at any time and experienced a significant AE considered related to IT administration that, in the opinion of the investigator, would put the participant at undue risk.
• Has received IV laronidase at any time and experienced a significant AE considered related to IV administration that, in the opinion of the investigator, would put the participant at undue risk.
• Has imminent plans to receive HSCT within the next year.
• Has any history of lymphoma or history of another cancer other than squamous cell or basal cell carcinoma of the skin that has not been in full remission for at least 3 months before screening.
• Has uncontrolled hypertension (systolic BP \> 180 mmHg, diastolic BP \> 100 mmHg) despite maximal medical treatment.
• Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3 × ULN or total bilirubin \> 1.5 × ULN at screening, unless the participant has a previously known history of Gilbert's syndrome and a fractionated bilirubin that shows conjugated bilirubin \< 35% of total bilirubin.

Sponsors & Collaborators

• REGENXBIO Inc.: lead

Study Sites (2)

Children's Hospital of Orange County

Orange, California, 92868, United States

Location

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Related Publications (1)

• De BP, Rosenberg JB, Selvan N, Wilson I, Yusufzai N, Greco A, Kaminsky SM, Heier LA, Ricart Arbona RJ, Miranda IC, Monette S, Nair A, Khanna R, Crystal RG, Sondhi D. Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease. Hum Gene Ther. 2023 Sep;34(17-18):905-916. doi: 10.1089/hum.2023.067.

  PMID: 37624739 DERIVED

MeSH Terms

Conditions

Mucopolysaccharidosis I

Condition Hierarchy (Ancestors)

Mucopolysaccharidoses; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lysosomal Storage Diseases; Mucinoses; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open-Label
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Sequential Assignment Dose escalation

Study Record Dates

• First Submitted: June 18, 2018
• First Posted: July 9, 2018
• Study Start: April 3, 2019
• Primary Completion (Estimated): July 7, 2027
• Study Completion (Estimated): March 6, 2029
• Last Updated: March 12, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); BR (1)