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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04088734




Registration number
NCT04088734
Ethics application status
Date submitted
11/09/2019
Date registered
13/09/2019
Date last updated
26/06/2020

Titles & IDs
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
Secondary ID [1] 0 0
ABT-003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
MPS IIIA 0 0
Sanfilippo Syndrome 0 0
Sanfilippo A 0 0
Mucopolysaccharidosis III 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - ABO-102

Experimental: ABO-102 -


Treatment: Drugs: ABO-102
Single dose of ABO-102 (scAAV9.U1a.hSGSH) administered by intravenous injection through a peripheral limb vein at a dose of 3 X 10^13 vg/kg

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Adverse Events and Serious Adverse Events - The incidence, type, and severity of treatment-related adverse events and serious adverse events
Timepoint [1] 0 0
24 months
Primary outcome [2] 0 0
CSF Heparan Sulfate - Change from baseline in CSF heparan sulfate levels after treatment
Timepoint [2] 0 0
1, 6, 12, 24 months
Primary outcome [3] 0 0
Liver and/or Spleen Volumes - Change from baseline in liver and/or spleen volumes after treatment, as measured by MRI
Timepoint [3] 0 0
1, 6, 12, 24 months
Secondary outcome [1] 0 0
Glycosaminoglycans or Heparan Sulfate - Change from baseline in plasma or urine glycosaminoglycans or heparan sulfate after treatment
Timepoint [1] 0 0
1, 6, 12, 18, 24 months
Secondary outcome [2] 0 0
SGSH Enzyme Activity - Change from baseline in CSF or plasma or leukocyte SGSH enzyme activity levels after treatment
Timepoint [2] 0 0
1, 6, 12, 24 Months
Secondary outcome [3] 0 0
Brain Volume - Change from baseline in brain volume after treatment, as measured by MRI
Timepoint [3] 0 0
12, 24 months
Secondary outcome [4] 0 0
Developmental Quotient - Change from baseline in the Developmental Quotient after treatment compared to Natural History Study data calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, 2nd edition, based on chronological and developmental age
Timepoint [4] 0 0
6, 12, 18, 24 months
Secondary outcome [5] 0 0
Age Equivalent - Change from baseline in the Age Equivalent after treatment compared to Natural History Study data calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, 2nd edition, based on chronological and developmental age
Timepoint [5] 0 0
6, 12, 18, 24 months
Secondary outcome [6] 0 0
Cognitive 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
Timepoint [6] 0 0
6, 12, 18, 24 months
Secondary outcome [7] 0 0
Cognitive Age Equivalent - Change from baseline in the Cognitive Age Equivalent 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
Timepoint [7] 0 0
6, 12, 18, 24 months
Secondary outcome [8] 0 0
Adaptive Age Equivalent Score - 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
Timepoint [8] 0 0
6, 12, 18, 24 months
Secondary outcome [9] 0 0
Sleep Pattern - Change from baseline in sleep pattern as measured by the modified Children's Sleep Habits Questionnaire (CSHQ)
Timepoint [9] 0 0
6, 12, 18, 24 months
Secondary outcome [10] 0 0
Pediatric Quality of Life Inventory - Change from baseline in Pediatric Quality of Life Inventory (PedsQL™) Core Generic Scales total score
Timepoint [10] 0 0
6, 12, 18, 24 months
Secondary outcome [11] 0 0
Parent Quality of Life - Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4)
Timepoint [11] 0 0
6, 12, 18, 24 months
Secondary outcome [12] 0 0
Gastrointestinal Symptoms - Change from baseline in gastrointestinal symptoms using the PedsQL™ Gastrointestinal Symptoms Scales
Timepoint [12] 0 0
6, 12, 18, 24 months
Secondary outcome [13] 0 0
Parent Global Impression Score - Parent Global Impression Score at different time points
Timepoint [13] 0 0
6, 12, 18, 24 months
Secondary outcome [14] 0 0
Clinical Global Impression Improvement Scale - Clinical Global Impression Improvement Score at different time points.
Timepoint [14] 0 0
6, 12, 18, 24 months
Secondary outcome [15] 0 0
Parent Symptoms Score Questionnaire - Change from baseline in Parent Symptoms Score Questionnaire
Timepoint [15] 0 0
6, 12, 18, 24 months
Secondary outcome [16] 0 0
Body Mass Index - Change from baseline in Body Mass Index after treatment
Timepoint [16] 0 0
6, 12, 18, 24 months
Secondary outcome [17] 0 0
EEG Monitoring - Incidence and Change from baseline in abnormalities in standard awake 45-minutes- EEG monitoring
Timepoint [17] 0 0
6, 12, 18, 24 months
Secondary outcome [18] 0 0
AAV9 Viral DNA Detection - Detection of the AAV9 viral DNA in plasma, saliva, urine and feces will provide preliminary data for the Environmental Risk Assessment (ERA)
Timepoint [18] 0 0
24 months

Eligibility
Key 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)
Minimum age
No limit
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1/Phase 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 0 0
Adelaide Women's and Children's Hospital - North Adelaide
Recruitment postcode(s) [1] 0 0
5006 - North Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Pennsylvania
Country [2] 0 0
Spain
State/province [2] 0 0
Santiago De Compostela

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Abeona Therapeutics, Inc
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Open-label, clinical trial of scAAV9.U1a.hSGSH injected intravenously through a peripheral
limb vein
Trial website
https://clinicaltrials.gov/show/NCT04088734
Trial related presentations / publications
Fu H, Cataldi MP, Ware TA, Zaraspe K, Meadows AS, Murrey DA, McCarty DM. Functional correction of neurological and somatic disorders at later stages of disease in MPS IIIA mice by systemic scAAV9-hSGSH gene delivery. Mol Ther Methods Clin Dev. 2016 Jun 8;3:16036. doi: 10.1038/mtm.2016.36. eCollection 2016.
Fu H, Meadows AS, Pineda RJ, Kunkler KL, Truxal KV, McBride KL, Flanigan KM, McCarty DM. Differential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy Children and Patients with Mucopolysaccharidosis III: Perspective for AAV-Mediated Gene Therapy. Hum Gene Ther Clin Dev. 2017 Dec;28(4):187-196. doi: 10.1089/humc.2017.109. Epub 2017 Oct 24.
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Medical Affairs
Address 0 0
Country 0 0
Phone 0 0
+1 646-813-4701
Fax 0 0
Email 0 0
sanfilippo@abeonatherapeutics.com
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT04088734