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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT04088734
Ethics application status
Date submitted
11/09/2019
Date registered
13/09/2019
Date last updated
25/07/2023

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
UX111-CL201
Secondary ID [2] 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 - Dose of 3x10\^13 vg/kg


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
Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame
Timepoint [1] 0 0
From the first dose of study drug to <30 days postdose, Day 30, 60, 90, 180 and Month 12
Primary outcome [2] 0 0
Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame
Timepoint [2] 0 0
From signing of informed consent through Day 60, 90, 180 and up to Day 454 (> 12 months)
Primary outcome [3] 0 0
Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment
Timepoint [3] 0 0
Baseline, Day 30, 180, Month 12
Primary outcome [4] 0 0
Change From BL in Cerebrospinal Fluid (CSF) Heparan Sulfate Levels After Treatment
Timepoint [4] 0 0
Baseline, Day 30, Day 180, Month 12
Secondary outcome [1] 0 0
Change From Baseline in Plasma Heparan Sulfate After Treatment
Timepoint [1] 0 0
Baseline, Day 30, Day 180, Month 12
Secondary outcome [2] 0 0
Change From Baseline in Urine Glycosaminoglycans After Treatment
Timepoint [2] 0 0
Baseline, Day 30, Day 180, Month 12
Secondary outcome [3] 0 0
Change From Baseline in Urine Heparan Sulfate After Treatment
Timepoint [3] 0 0
Baseline, Day 30, Day 180, Month 12
Secondary outcome [4] 0 0
Change From Baseline in CSF N-Sulfoglucosamine Sulfohydrolase (SGSH) Enzyme Activity Levels After Treatment
Timepoint [4] 0 0
Baseline, Day 30, Day 180, and Month 12
Secondary outcome [5] 0 0
Change From Baseline in Heparan N-Sulfatase (Type A) After Treatment
Timepoint [5] 0 0
Baseline, Day 30, Day 180, Month 12
Secondary outcome [6] 0 0
Change From Baseline in Plasma SGSH After Treatment
Timepoint [6] 0 0
Baseline, Day 30, Day 180, Month 12
Secondary outcome [7] 0 0
Change From Baseline in Brain Volumes After Treatment
Timepoint [7] 0 0
Baseline, 12 months
Secondary outcome [8] 0 0
Change From Baseline in Brain Volumes After Treatment: Average Total Cortical Thickness
Timepoint [8] 0 0
Baseline, 12 months
Secondary outcome [9] 0 0
Change From Baseline in Sleep Pattern as Measured by the Modified Children's Sleep Habits Questionnaire (CSHQ) Subscore Total After Treatment
Timepoint [9] 0 0
Baseline, Day 180, Month 12
Secondary outcome [10] 0 0
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Core Generic Scales Total Score
Timepoint [10] 0 0
Baseline, Day 180, Month 12
Secondary outcome [11] 0 0
Change From Baseline in Parent Quality of Life, Using the Parenting Stress Index, 4th Edition (PSI-4) Total Stress Raw Score
Timepoint [11] 0 0
Baseline, Day 180, Month 12
Secondary outcome [12] 0 0
Change From Baseline in Gastrointestinal Symptoms Using the PedsQL™ Gastrointestinal (GI) Symptoms Scales Score
Timepoint [12] 0 0
Baseline, Day 180, Month 12
Secondary outcome [13] 0 0
Change From Baseline in Parent Global Impression (PGI) Total Score
Timepoint [13] 0 0
Baseline, Day 180, Month 12
Secondary outcome [14] 0 0
Clinical Global Impression Improvement Scale at Day 180 and Month 12
Timepoint [14] 0 0
Day 180, Month 12
Secondary outcome [15] 0 0
Change From Baseline in Parent Symptoms Score Questionnaire
Timepoint [15] 0 0
Baseline, Day 180, Month 12
Secondary outcome [16] 0 0
Percent Change From Baseline in Body Mass Index After Treatment
Timepoint [16] 0 0
Baseline, Day 30, Day 180, Month 12
Secondary outcome [17] 0 0
Number of Participants With Abnormalities in Standard Awake 45-Minutes-Electroencephalogram (EEG) Monitoring at Baseline and Day 180
Timepoint [17] 0 0
Baseline, Day 180
Secondary outcome [18] 0 0
Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine
Timepoint [18] 0 0
Baseline, Day 30, Day 180, Month 12

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
2 Years
Maximum age
18 Years
Sex
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
Not applicable
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
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
18/09/2019
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
10/03/2022
Sample size
Target
Accrual to date
Final
5
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
Ultragenyx Pharmaceutical Inc
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Abeona Therapeutics, Inc
Address [1] 0 0
Country [1] 0 0

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/study/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
Medical Director
Address 0 0
Ultragenyx Pharmaceutical Inc
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

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