Mucopolysaccharidosis type I
Conditions
Interventions
Approximately 5 subjects will be treated in 2 dose cohorts (dose groups), 1 × 10e10 Genome Copies (GC)/g brain mass (n=2) or 5 × 10e10 Genome Copies (GC)/g brain mass (n=3) and will receive a single
Drug
E02.095.301
Sponsors
Hospitais de Clínicas de Porto Alegre
REGENXBIO Inc.
Medpace do Brasil Pesquisa Clínica Ltda.
Eligibility
Age
0 Months to 3 Years
Inclusion criteria
Inclusion criteria: A male or female less than 3 years of age; 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; Has a documented diagnosis of severe Mucopolysaccharidosis Type I (MPS I) -Hurler confirmed by homozygosity or compound heterozygosity for mutations exclusively associated with the severe phenotype; Has an intelligent quotient (IQ) score of greater than or equal to 55; 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
Exclusion criteria
Exclusion criteria: Has a contraindication for an intracisternal injection (IC); Has any neurocognitive deficit not attributable to Mucopolysaccharidosis Type I (MPS I) or has a diagnosis of a neuropsychiatric condition that may, in the opinion of the PI, confound interpretation of study results; Has any contraindication to lumbar puncture; Has undergone hematopoetic stem cell transplantation (HSCT); Has had prior treatment with an Adeno-associated virus (AAV)-based gene therapy product; Has received intrathecal (IT) laronidase at any time and experienced a significant Adverse event (AE) considered related to IT administration that, in the opinion of the PI, would put the subject at undue risk; Has a platelet count less than 100,000 per microliter; Has alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 3 × upper limit of normal (ULN) or total bilirubin greater than 1.5 × ULN at screening, unless the subject has a previously known history of Gilbert’s syndrome; Has a history of human immunodeficiency virus (HIV) or hepatitis B or hepatitis C virus infection, or positive screening tests for hepatitis B surface antigen or hepatitis B core antibody, or hepatitis C or HIV antibodies
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Expected outcome 1: Safety through Week 24: Adverse event(s) and serious adverse events (SAEs) | — |
Secondary
| Measure | Time frame |
|---|---|
| Expected outcome 1: Pharmacodynamics biomarkers in plasma (GAGs and IDUA), Cerebrospinal fluid (GAGs, IDUA and spermin), and urine (GAGs) ;Expected outcome 2: Validated instruments for intelligence quotient (IQ) [Bayley Scale of Infant and Toddler Development, Third Edition (Bayley-III) and/or the Wechsler Preschool and Primary Scales of Intelligence, Fourth Edition (WPPSI-IV)] and adaptive behavior (Vineland-2);Expected outcome 3: Safety through Week 104: Adverse event reporting, laboratory evaluations, vital signs, Electrocardiograms, physical examinations, and neurologic assessments;Expected outcome 4: Vector concentration (quantitative polymerase chain reaction [qPCR] to RGX-111 deoxyribonucleic acid [DNA]) in Cerebrospinal fluid, serum, and urine | — |
Countries
Brazil
Contacts
Public ContactFernando ;Lisa DÀgostino;Carlton
Medpace do Brasil Pesquisa Clínica Ltda.;REGENXBIO Inc.
Outcome results
None listed