start date: October 29, 2019
estimated completion: December 2023
last updated: January 24, 2022
phase of development:
Phase 1/Phase 2
size / enrollment: 12
study description: This is an open-label, single dose clinical trial. All participants will receive 3 X 10^13 vg/kg of ABO-102 delivered one time through a venous catheter inserted into a peripheral limb vein. The target population includes MPS IIIA participants with a DQ lower than 60 in middle and advanced phases of the disease. Similar numbers of MPS IIIA participants with age equivalent above and below 18 months of age will be enrolled to ensure a representation of middle and advanced phases of the disease.
primary outcomes:
- Adverse Events and Serious Adverse Events
The incidence, type, and severity of treatment-related adverse events and serious adverse events
- 24 months
CSF Heparan Sulfate
Change from baseline in CSF heparan sulfate levels after treatment
- 1, 6, 12, 24 months
Liver and/or Spleen Volumes
Change from baseline in liver and/or spleen volumes after treatment, as measured by MRI
- 1, 6, 12, 24 months
secondary outcomes:
- Glycosaminoglycans or Heparan Sulfate
1, 6, 12, 18, 24 months
- SGSH Enzyme Activity
1, 6, 12, 24 Months
- Brain Volume
12, 24 months
- Age Equivalent
6, 12, 18, 24 months
- Mullen Developmental Quotient
6, 12, 18, 24 months
- Cognitive Age Equivalent
6, 12, 18, 24 months
- Bayley Developmental Quotient
6, 12, 18, 24 months
- Adaptive Age Equivalent Score
6, 12, 18, 24 months
- Sleep Pattern
6, 12, 18, 24 months
- Pediatric Quality of Life Inventory Core
6, 12, 18, 24 months
- Parent Quality of Life
6, 12, 18, 24 months
- Pediatric Quality of Life Inventory Gastrointestinal
6, 12, 18, 24 months
- Parent Global Impression Score
6, 12, 18, 24 months
- Clinical Global Impression Improvement Scale
6, 12, 18, 24 months
- Parent Symptoms Score Questionnaire
6, 12, 18, 24 months
- Body Mass Index
6, 12, 18, 24 months
- EEG Monitoring
6, 12, 18, 24 months
- AAV9 Viral DNA Detection
24 months
inclusion criteria:
• Eligible Ages: 0 - 120
• Eligible Sexes: all
Inclusion Criteria:
Diagnosis of MPS IIIA confirmed by the following methods:
No detectable or significantly reduced SGSH enzyme activity by leukocyte assay and
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
Age range of 2 years up to 18 years (excluded)
exclusion criteria: 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 greater than or equal to 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 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 (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 v4.03
