Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease

study id #: NCT04088734

condition: MPS IIIA, Sanfilippo Syndrome, Sanfilippo A, Mucopolysaccharidosis III

status: Recruiting

Open-label, clinical trial of scAAV9.U1a.hSGSH injected intravenously through a peripheral limb vein

intervention: ABO-102

results: https://clinicaltrials.gov/ct2/show/results/NCT04088734

last updated: February 26, 2022

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:

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

sponsor: Abeona Therapeutics, Inc

contacts: Medical Affairs, +1 646-813-4701, sanfilippo@abeonatherapeutics.com

trial center locations: Australia,Spain

• United States, Pennsylvania
  Children’s Hospital of Pittsburgh
  Maria L Escolar, MD, MS, 412-692-6350, maria.escolar@chp.edu
  
  
• Australia, South Australia
  Adelaide Women’s and Children’s Hospital
  Louise Jaensch, +61 08 8161 7295, louise.jaensch@sa.gov.au
  
  
• Spain
  Hospital Clínico Universitario de Santiago
  Maria Luz Couce, MD, PhD, maria.luz.couce.pico@sergas.es