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

• Register: ClinicalTrials.gov
• Last refreshed on: 23 January 2023
• Main ID: NCT04088734
• Date of registration: 11/09/2019
• Prospective Registration: Yes
• Primary sponsor: Ultragenyx Pharmaceutical Inc
• Public title: Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease
• Scientific title: A Phase I/II Open Label, Single-dose, Gene Transfer Study of scAAV9.U1a.hSGSH (ABO-102) in Patients With Middle and Advanced Phases of MPS IIIA Disease
• Date of first enrolment: September 18, 2019
• Target sample size: 5
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT04088734
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Spain, United States

Contacts

• Name: Medical Director
• Affiliation: Ultragenyx Pharmaceutical Inc

Key inclusion & exclusion criteria

Inclusion Criteria:

- Diagnosis of MPS IIIA confirmed by the following methods:

1. No detectable or significantly reduced SGSH enzyme activity by leukocyte assay
and

2. 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:

- 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



Age minimum: 2 Years
Age maximum: 18 Years
Gender: All

Health Condition(s) or Problem(s) studied

Sanfilippo Syndrome

Mucopolysaccharidosis III

MPS IIIA

Sanfilippo A

Intervention(s)

Drug: ABO-102

Primary Outcome(s)

Liver and/or Spleen Volumes [Time Frame: 1, 6, 12, 24 months]

CSF Heparan Sulfate [Time Frame: 1, 6, 12, 24 months]

Adverse Events and Serious Adverse Events [Time Frame: 24 months]

Secondary Outcome(s)

Cognitive Age Equivalent [Time Frame: 6, 12, 18, 24 months]

AAV9 Viral DNA Detection [Time Frame: 24 months]

Age Equivalent [Time Frame: 6, 12, 18, 24 months]

Brain Volume [Time Frame: 12, 24 months]

Parent Symptoms Score Questionnaire [Time Frame: 6, 12, 18, 24 months]

Body Mass Index [Time Frame: 6, 12, 18, 24 months]

Clinical Global Impression Improvement Scale [Time Frame: 6, 12, 18, 24 months]

Glycosaminoglycans or Heparan Sulfate [Time Frame: 1, 6, 12, 18, 24 months]

Sleep Pattern [Time Frame: 6, 12, 18, 24 months]

Parent Global Impression Score [Time Frame: 6, 12, 18, 24 months]

Bayley Developmental Quotient [Time Frame: 6, 12, 18, 24 months]

SGSH Enzyme Activity [Time Frame: 1, 6, 12, 24 Months]

Pediatric Quality of Life Inventory Gastrointestinal [Time Frame: 6, 12, 18, 24 months]

Adaptive Age Equivalent Score [Time Frame: 6, 12, 18, 24 months]

Pediatric Quality of Life Inventory Core [Time Frame: 6, 12, 18, 24 months]

EEG Monitoring [Time Frame: 6, 12, 18, 24 months]

Mullen Developmental Quotient [Time Frame: 6, 12, 18, 24 months]

Parent Quality of Life [Time Frame: 6, 12, 18, 24 months]

Secondary ID(s)

ABT-003

UX111-CL201

2018-000504-42

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Abeona Therapeutics, Inc