Gene transfer clinical trial for Mucopolysaccharidosis IIIA

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: Not specified

Target Recruitment: 22

Inclusion Criteria

• Diagnosis of MPS IIIA confirmed by the following methods:
o No detectable or significantly reduced SGSH enzyme activity by leukocyte assay, and
o Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the SGSH gene
• Age 6 months to 2 years or children older than 2 years with a minimum cognitive Development Quotient (DQ) of 60 or above (calculated by Bayley Scales of Infant and Toddler Development - Third Edition)
Are the trial subjects under 18? yes
Number of subjects for this age range: 22
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

• Inability to participate in the clinical evaluation as determined by Principal Investigator
• Identification of two nonsense or null variants on genetic testing of the SGSH gene
• At least one S298P mutation in the SGSH gene
• Has evidence of an attenuated phenotype of MPS IIIA
• Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
• Active viral infection based on clinical observations
• Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer, or precludes the child from participating in the protocol assessments and follow up
• Subjects with total anti-AAV9 antibody titers = 1:100 as determined by ELISA binding immunoassay
• Subjects with a positive response for the ELISPOT for T-cell responses to AAV9
• Serology consistent with exposure to HIV, or serology consistent with active hepatitis B or C infection
• Bleeding disorder or any other medical condition or circumstance in which a lumbar puncture (for collection of CSF) is contraindicated according to local institutional policy
• Visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing
• Uncontrolled seizure disorder
• Any item (braces, etc.) which would exclude the subject from being able to undergo MRI according to local institutional policy
• Any other situation that precludes the subject from undergoing procedures required in this study
• Subjects with cardiomyopathy or significant congenital heart abnormalities
• The presence of significant non-MPS IlIA related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
• Abnormal laboratory values Grade 2 or higher as defined in CTCAE v4.03 for GGT, total bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT and aPTT
• Female participant who is pregnant or demonstrates a positive urine or ßhCG result at screening assessment (if applicable).
• Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone)
• Previous treatment by Haematopoietic Stem Cell transplantation
• Previous participation in a gene/cell therapy or ERT clinical trial

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

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