MPS IIIA is a devastating lysosomal storage disease, caused by a N-sulfoglucosamine sulfohydrolase gene defect. Infants with MPS IIIA appear normal at birth, but the disease is relentlessly progressive, with deterioration of social and adaptive abilities, neurocognitive decline, and premature death. Death typically occurs by end of the second or beginning of the third decade. Quite importantly, there is no treatment currently available for the disease.
Conditions
Interventions
Product Name: scAAV9.U1A.SGSH
Product Code: scAAV9.U1A.SGSH
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: scAAV9.U1A.SGSH
Current Sponsor code: scAAV9.U1A
Sponsors
Abeona Therapeutics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Age 6 months old or greater 2.Confirmed diagnosis of MPS IIIA by both of the following methods: a.No detectable or significantly reduced SGSH enzyme activity by leukocyte assay b.Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the SGSH gene 3.Clinical history or examination features of neurologic dysfunction Are the trial subjects under 18? yes Number of subjects for this age range: 18 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1.Inability to participate in the clinical evaluation as determined by principal investigator 2.Identification of two nonsense or null variants on genetic testing of the SGSH gene, as judged by the principal investigator 3.Has evidence of an attenuated phenotype of MPS IIIA, as judged by the principal investigator 4.Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics 5.Inability to be safely sedated in the opinion of the clinical anesthesiologist 6.Active viral infection based on clinical observations 7.Concomitant illness or requirement for chronic drug treatment that in the opinion of the Principal Investigatior (PI) creates unnecessary risks for gene transfer 8.Subjects with total anti-AAV9 antibody titers > or = 1:100 as determined by ELISA binding immunoassay 9.Serology consistent with exposure to HIV, or serology consistent with active hepatitis B or C infection 10.Bleeding disorder or any other medical condition or circumstance in which a lumbar puncture (for collection of cerebrospinal fluid (CSF)) is contraindicated according to local institutional policy 11.Visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing 12.Uncontrolled seizure disorder, due to the requirement for multiple Magnetic Resonance Imagine (MRI) examinations as part of the study protocol. Subjects who are stable on anticonvulsive medications may be included 13.Any item (braces, etc.) which would exclude the subject from being able to undergo MRI according to local institutional policy 14.Any other situation that would exclude the subject from undergoing any other procedure required in this study 15.Subjects with cardiomyopathy or significant congenital heart abnormalities 16.The presence of significant non-MPS IIIA related Central Nervous System (CNS) impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study 17.Abnormal laboratory values Grade 2 or higher as defined in CTCAE v4.0, for GGT, total bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT and a PTT 18.Female participant who is pregnant or demonstrates a positive urine or serum ß-HCG result at screening assessment (if applicable).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Determination of safety based on the development of unacceptable toxicity;Secondary Objective: 1.Reduction of CSF, plasma or urine glycosaminoglycans or heparan sulfate at 6 and/or 12 months after treatment 2.Increase in CSF or plasma or leukocyte SGSH enzyme activity levels at 6 and/or 12 months after treatment 3.Reduced liver and/or spleen volumes at 6 and/or 12 months after treatment, as measured by MRI 4.Improved adaptive functioning, or arrest of decline in adaptive functioning at 6 and/or 12 months after treatment, as assessed by parent report using the Vineland Adaptive Behavior Scale II 5.Improved cognitive ability or arrest of cognitive deterioration at 6 and/or 12 months after treatment, as measured by direct testing of the child using the Leiter International Performance Scale (brief IQ), the Mullen Scales of Early Learning; and by parent report using the Sanfilippo Behavior Rating Scale.;Primary end point(s): Determination of safety: Adverse events and Serious Adverse events;Timepoint(s) of evaluation of this end point: Adverse events will be evaluated along the entire trial during 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Reduction of CSF , plasma or urine glycosaminoglycans or heparan sulfate at 6 and/or 12 months after treatment. 2.Increase in CSF, plasma or leukocytes SGSH enzyme activity levels at 6 and/or 12 months after treatment. 3.Reduced liver and/or spleen volumes at 6 and/or 12 months after treatment, as measured by MRI. 4.Improved adaptive functioning, or arrest of decline in adaptive functioning at 6 and/or 12 months after treatmnt, as assessed by parent report using appropiate scale. 5.Improved cognitive ability or arrest of cognitive deterioration at 6 and/or 12 months after treatment, as measured by direct testing of the child and by parent report using the appropiate scales.;Timepoint(s) of evaluation of this end point: - Day -45 to -1 (patient inclusion); day1, 7, 14, 30, 60, 90, 180, month 12, month 18, month 24 - Day -45 to -1 (patient inclusion); day 7, 14, 30, 60, 90, 180, month 12, month 18, month 24 - Day -45 to -1 (patient inclusion); days 30, 180, month 12, month 24 - Day -45 to -1: day 180, month 12, month 18, month 24 - Day -45 to -1: day 180, month 12, month 18, month 24 | — |
Countries
Australia, Spain, United States
Contacts
Public ContactJuan Ruiz
Abeona Therapeutics Inc
Outcome results
None listed