MPS IIIA is a devastating lysosomal storage disease, caused by a Nsulfoglucosamine 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 Level: PT Classificati
Conditions
Interventions
Product Name: scAAV9.U1A.SGSH
Product Code: ABO-102
Pharmaceutical Form: Suspension for injection
INN or Proposed INN: scAAV9.U1A.SGSH
Current Sponsor code: scAAV9.U1A.SGSH
Other descriptive name: scA
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 • Cognitive Development Quotient (DQ) lower than 60 (calculated by Bayley Scales of Infant and Toddler Development - Third Edition) • Must be ambulatory, though may receive assistance with ambulation Are the trial subjects under 18? yes Number of subjects for this age range: 12 F.1.2 Adults (18-64 years) no F.1.2.1 Number of subjects for this age range 0 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
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 • Participants with total anti-AAV9 antibody titers = 1:100 as determined by ELISA binding immunoassay • Participants 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 • Any item (braces, etc.) which would exclude the participant from being able to undergo MRI according to local institutional policy • Any other situation that precludes the participant from undergoing procedures required in this study • Participants with cardiomyopathy or significant congenital heart abnormalities • The 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 CTCAE v4.0 for GGT, total bilirubin (except in subjects diagnosed with Gilbert’s syndrome), creatinine, hemoglobin, WBC count, platelet count, PT and aPTT • Female participant who is pregnant or demonstrates a positive urine or beta-hCG 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 • Participants who are anticipated to undergo a procedure involving anesthesia within 6 months post- drug administration • Dysphagia present at Grade 3 or higher, as defined in CTCAE v4.0
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary outcomes of safety and efficacy assessed by measuring biochemical and biophysical changes in middle and advanced phases of MPS IIIA evolution;Secondary Objective: Change from baseline: • in plasma or urine GAG or HS after treatment (AT) • in CSF or plasma or leukocyte SGSH enzyme activity levels AT • in brain volumes AT • in the Developmental Age AT compared to Natural History Study (NHS) • in the Cognitive Developmental Age AT compared to NHS • in the Adaptive Age Equivalent score AT compared to NHS • in the Sanfilippo Behavior Rating Scale • in sleep pattern • in Pediatric Quality of Life Inventory Core Generic Scales total • in parent quality of life • Change from baseline in gastrointestinal symptoms • in Parent Global Impression Score • in Clinical Global Impression Improvement Scale • in Parent Symptoms Score Questionnaire • in Body Mass Index AT • and incidence in abnormalities in standard awake 60-minutes- EEG monitoring Preliminary data for the Environmental Risk Assessment;Primary end point(s): • Product safety as defined by the incidence, type and severity of treatment-related adverse events and serious adverse events • Change from baseline in CSF heparan sulfate levels after treatment • Change from baseline in liver and/or spleen volumes after treatment, as measured by magnetic resonance imaging (MRI);Timepoint(s) of evaluation of this end point: - Month 1, 2, 3, 6, 12, 18, 24 - Month 1, 6, 12, 24 - Month 1, 6, 12, 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Change from baseline in 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 brain volumes after treatment, as measured by MRI • Change from baseline in the Developmental Age after treatment compared to Natural History Study data calculated 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 Cognitive Developmental Age after treatment 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 in the Sanfilippo Behavior Rating Scale • Change from baseline in sleep pattern as measured by the modified Children’s Sleep Habits Questionnaire (CSHQ) • Change from baseline in Pediatric Quality of Life Inventory (PedsQL™) Core Generic Scales total score • Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4) • Change from baseline in gastrointestinal symptoms using the PedsQL™ Gastrointestinal Symptoms Scales • Change from baseline in Parent Global Impression Score • Change from baseline in Clinical Global Impression Improvement Scale • Change from baseline in Parent Symptoms Score Questionnaire • Change from Baseline in Body Mass Index after treatment • Incidence and Change from baseline in abnormalities in standard awake 60-minutes- EEG monitoring • Determination of vector shedding analysis in plasma, saliva, urine and feces will provide preliminary data | — |
Countries
Australia, Spain, United States
Contacts
Public ContactHead of European Medical Affairs
Abeona Therapeutics Inc
Outcome results
None listed