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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02716246




Registration number
NCT02716246
Ethics application status
Date submitted
17/03/2016
Date registered
23/03/2016
Date last updated
26/06/2020

Titles & IDs
Public title
Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
Scientific title
Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA
Secondary ID [1] 0 0
ABT001
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
Other interventions - ABO-102

Experimental: Cohort 1 Low Dose - Dose of 0.5 X 10^13 vg/kg

Experimental: Cohort 2 Mid Dose - Dose of 1 X 10^13 vg/kg

Experimental: Cohort 3 High Dose - Dose of 3 X 10^13 vg/kg


Other interventions: ABO-102
Self-complementary adeno-associated virus serotype 9 carrying the human SGSH gene under the control of a U1a promoter (scAAV9.U1a.hSGSH) will be delivered one time through a venous catheter inserted into a peripheral limb vein.

Intervention code [1] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Product safety - Determination of safety based on the development of unacceptable toxicity: defined as the occurrence of two or more unanticipated Grade III or higher treatment-related adverse events.
Timepoint [1] 0 0
24 months
Primary outcome [2] 0 0
Change from baseline in age equivalent developmental score - Change from baseline in the Age Equivalent Developmental Score calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, based on developmental age, compared with natural history study data at 6, 12, 18, and 24 months
Timepoint [2] 0 0
24 months
Secondary outcome [1] 0 0
Change from baseline of CSF heparan sulfate after treatment - Change from baseline of CSF heparan sulfate after treatment at 1, 6, 12, and 24 months
Timepoint [1] 0 0
24 months
Secondary outcome [2] 0 0
Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment - Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment at Month 1, 6, 12, 18, 24
Timepoint [2] 0 0
24 months
Secondary outcome [3] 0 0
Change from baseline in CSF or plasma or leukocyte SGSH enzyme activity levels after treatment - Change from baseline in CSF or plasma or leukocyte SGSH enzyme activity levels after treatment at Month 1, 6, 12, 24
Timepoint [3] 0 0
24 months
Secondary outcome [4] 0 0
Change from baseline in liver and/or spleen volumes after treatment - Change from baseline in liver and/or spleen volumes after treatment as measured by MRI at Month 1, 6, 12, 24
Timepoint [4] 0 0
24 months
Secondary outcome [5] 0 0
Change from baseline in brain volume after treatment - Change from baseline in brain volume after treatment as measured by MRI at Month 1, 6, 12, 24
Timepoint [5] 0 0
24 months
Secondary outcome [6] 0 0
Change from baseline in Cognitive Age Equivalent (Developmental Age) - Change from baseline in Cognitive Age Equivalent (Developmental Age) compared to natural history study calculated using the Bayley Scales of Infant and Toddler Development or the Kaufman Assessment Battery for Children at Month 6, 12, 18, 24
Timepoint [6] 0 0
24 months
Secondary outcome [7] 0 0
Change from baseline in Adaptive Age Equivalent score - Change from baseline in 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 at Month 6, 12, 18, 24
Timepoint [7] 0 0
24 months
Secondary outcome [8] 0 0
Change from baseline Developmental Quotient - Change from baseline Developmental Quotient after treatment compared to natural history study data assessed by Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, based on chronological and developmental age, at Month 6, 12, 18, 24
Timepoint [8] 0 0
24 months
Secondary outcome [9] 0 0
Change from baseline in the Sanfilippo Behavior Rating Scale - Change from baseline in the Sanfilippo Behavior Rating Scale at Month 6, 12, 18, 24
Timepoint [9] 0 0
24 months
Secondary outcome [10] 0 0
Change from baseline in the Leiter International Performance Scale - Revised - Change from baseline in the Leiter-R at Month 6, 12, 18, 24
Timepoint [10] 0 0
24 months
Secondary outcome [11] 0 0
Change from baseline in Pediatric Quality of Life Inventory (PedsQL) total score - Change from baseline in Pediatric Quality of Life Inventory (PedsQL) total score at Month 6, 12, 18, 24
Timepoint [11] 0 0
24 months
Secondary outcome [12] 0 0
Change from baseline in parent quality of life, using the Parenting Stress Index, 4th ed. - Change from baseline in parent quality of life, using the Parenting Stress Index, 4th ed short form (PSI-4) at Month 12, 24
Timepoint [12] 0 0
24 months
Secondary outcome [13] 0 0
Determination of vector shedding analysis - Determination of vector shedding in plasma, saliva, urine, and feces to provide preliminary data for the Environmental Risk Assessment
Timepoint [13] 0 0
24 months

Eligibility
Key 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

- Age 6 months to 2 years or children older than 2 years with a minimum cognitive
Developmental Quotient (DO) of 60 or above (calculated by Bayley Scales of lnfant and
Toddler Development - Third Edition)
Minimum age
6 Months
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 PI

- 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

- Subjects with total anti-AAV9 antibody titers = 1:100 as determined by ELISA binding
immunoassay

- Subjects 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

- Uncontrolled seizure disorder

- Any item (braces, etc.) which would exclude the subject from being able to undergo MRI
according to local institutional policy

- Any other situation that precludes the subject from undergoing procedures required in
this study

- Subjects 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, creatinine, hemoglobin, WBC count, platelet count, PT and aPTT

- Female participant who is pregnant or demonstrates a positive urine or bhCG 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
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
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
Ohio
Country [2] 0 0
United States of America
State/province [2] 0 0
Pennsylvania
Country [3] 0 0
Spain
State/province [3] 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, dose-escalation clinical trial of scAAV9.U1a.hSGSH injected intravenously through
a peripheral limb vein
Trial website
https://clinicaltrials.gov/show/NCT02716246
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/NCT02716246