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. MedDRA version: 20.1
Conditions
Interventions
Product Name: scAAV9.U1A.hSGSH
Product Code: ABO-102
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: rebisufligene etisparvovec
Sponsors
Abeona Therapeutics Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • Change from baseline in the Age Equivalent Developmental score compared with Natural History Study data • Product safety as defined by the occurrence of two or more treatment-related, unexpected Grade III or higher adverse events ; Secondary Objective: Change from baseline: • of CSF HS after treatment (AT) • of plasma or urine GAGs or HS AT • in CSF or plasma or leukocyte SGSH enzyme activity levels AT • in liver and/or and spleen volumes AT • in brain volumes AT • in the cognitive age equivalent compared to natural history study (NHS) • in the adaptive age equivalent score AT compared to NHS data • in the developmental quotient after treatment compared to NHS • in the Sanfilippo behavior rating scale • in the Leiter-R scale • in pediatric quality of life inventory total score • in parent quality of life •Preliminary data for the environmental risk assessment ; Primary end point(s): • Change from baseline in the Age Equivalent Developmental score (calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children Second Edition, based on developmental age) compared with Natural History Study data • Product safety as defined by the occurrence of two or more treatment-related, unexpected Grade III or higher adverse events ; Timepoint(s) of evaluation of this end point: - Month 6, 12, 18, 24 for change in the Age Equivalent Developmental score - Product safety will be evaluated along the entire trial for 24 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline of CSF heparan sulfate after treatment • Change from baseline of plasma or urine glycocaminoglycans or heparan sulfate after treatment • Change from baseline in CSF or plasma or leukocyte SGSH enzyme activity levels after treatment • Change from baseline in liver and/or and spleen volumes after treatment, as measured by magnetic resonance imaging (MRI) • Change from baseline in brain volumes after treatment, as measured by MRI • Change from baseline in the cognitive age equivalent (developmental age) compared to natural history study, calculated using the Bayley scales of infant and toddler development – Third edition or the Kaufman assessment battery for children. Second edition, based on developmental age • Change from baseline in the adaptive age equivalent score after treatment compared to natural history study data, as assessed by parent report using the Vineland adaptive behavior scale II survey form • Change from baseline developmental quotient after treatment compared to natural history study data assessed by the Mullen scales of early learning or the Kaufman assessment battery for children. Second edition, based on chronological and developmental age • Change from baseline in the Sanfilippo behavior rating scale • Change from baseline in the Leiter international performance scale – revised (Leiter-R) • Change from baseline in pediatric quality of life inventory (PedsQL™) total score • Change from baseline in parent quality of life, using the parenting stress index, 4th edition (PSI-4) short form • Determination of vector shedding analysis in plasma, saliva, urine and feces will provide preliminary data for the environmental risk assessment (ERA) ; Timepoint(s) of evaluation | — |
Countries
Australia, Brazil, France, Germany, Spain, United Kingdom, United States
Contacts
Public ContactHead of European Medical Affairs
Abeona Therapeutics Inc
Outcome results
None listed