Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 32

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: From 6 months to 2 years or children older than 2 years with a minimum Cognitive DQ of 60 or above (calculated by BSID-III)

Exclusion Criteria

Inability to participate in the clinical evaluation as determined by Principal Investigator, Serology consistent with exposure to human immunodeficient virus, or serology consistent with active hepatitis B or C infection, Bleeding disorder or any other medical condition or circumstance in which a LP (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, Yhe presence of significant non-MPS IIIA 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 Common Terminology Criteria for Adverse Events (CTCAE) v4.03 for gamma glutamyl transferase (GGT), total bilirubin, creatinine, hemoglobin, white blood cell (WBC) count, platelet count, prothrombin time (PT) and aPTT, Female participant who is pregnant or demonstrates a positive urine or beta hCG result at screening assessment (if applicable), Identification of two nonsense or null variants on genetic testing of the SGSH gene, Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone), Previous treatment by Hematopoietic Stem Cell transplantation, Previous participation in a gene/cell therapy or enzyme replacement therapy clinical trial., 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 > or = 1:100 equivalent to a positive screen as determined by ELISA in serum, Subjects with a positive response for the enzyme-linked immunosorbent spot (ELISpot) for T-cell responses to AAV9

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the efficacy and safety of ABO-102 for the treatment of mucopolysaccharidosis (MPS) IIIA;Secondary Objective: Not defined in the protocol;Primary end point(s): Safety: • Evaluate safety based on adverse events, incidence of treatment-emergent adverse events, and serious adverse events • Clinically significant changes in clinical laboratory assessments;, Efficacy: • Cognitive domain Bayley Scales of Infant and Toddler Development raw scores–Third edition (BSID-III). If applicable, according to the appropriate developmental age, non-verbal index raw scores for Kaufman Assessment Battery for Children, Second Edition (KABC-II) will also be used.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):Change from baseline in Vineland Adaptive Behavior Scale II-Survey Interview form;Secondary end point(s):Change from baseline in Mullen Scales of Early Learning;Secondary end point(s):Change from baseline in BSID-III (remaining domains);Secondary end point(s):If applicable, change from baseline in KABC-II (remaining domains);Secondary end point(s):Change from baseline of CSF heparan sulfate after treatment;Secondary end point(s):Change from baseline in CSF Gangliosides [GM2-GM3];Secondary end point(s):Change from baseline in brain total gray matter, total cortical gray matter, amygdala, and corpus collosum volumes as measured by MRI