Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
4 other identifiers
interventional
36
3 countries
5
Brief Summary
The main objective of this study is to evaluate the efficacy and safety of UX111 for the treatment of MPS IIIA.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
Started Apr 2016
Longer than P75 for phase_2
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 17, 2016
CompletedFirst Posted
Study publicly available on registry
March 23, 2016
CompletedStudy Start
First participant enrolled
April 25, 2016
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
July 1, 2027
April 24, 2026
April 1, 2026
11.2 years
March 17, 2016
April 21, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Cerebrospinal Fluid (CSF) Heparan Sulfate (HS) (Disaccharide) Exposure
Exposure is defined as the time-normalized area under the curve (AUC) of the percentage reduction from baseline.
Up to Month 24 Visit
Secondary Outcomes (7)
Bayley Scales of Infant and Toddler Development-Third Edition (BSITD-III) Cognitive Raw Score Over Time
Up to Month 24 Visit
CSF Ganglioside Type 2 (GM2) Exposure
Up to Month 24 Visit
CSF Ganglioside Type 3 (GM3) Exposure
Up to Month 24 Visit
Percent Change from Baseline in CSF HS
Baseline, Up to Month 24 Visit
BSITD-III Receptive Communication Raw Score Over Time
Up to Month 24 Visit
- +2 more secondary outcomes
Other Outcomes (1)
Number of Participants with Treatment-Emergent Adverse Events, and Treatment-Emergent Serious Adverse Events
Up to Month 24 Visit
Study Arms (4)
Cohort 1 Low Dose
EXPERIMENTALDose of 0.5 X 10\^13 vg/kg
Cohort 2 Mid Dose
EXPERIMENTALDose of 1 X 10\^13 vg/kg
Cohort 3 High Dose
EXPERIMENTALDose of 3 X 10\^13 vg/kg
Cohort 4 High Dose (Spain Only)
EXPERIMENTALDose of 3 X 10\^13 vg/kg
Interventions
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.
The Principal Investigator and/or caregiver, in consultation with the medical monitor, will determine whether to initiate adjuvant IM therapy. Not all participants may receive adjuvant IM therapy.
Eligibility Criteria
You may qualify if:
- 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 (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)
- Age:
- For Cohort 1-3: From birth (participating sites in USA and Australia) OR 6 months (participating sites in Spain) to 2 years of age with no BSITD-III Cognitive Development Quotient (DQ) requirement, or older than 2 years with a BSITD-III Cognitive DQ of 60 or above (participating sites globally).
- Cohort 4 only: Vaccination status based on age according to country-specific guidelines that is up to date 30 days prior to Enrollment as verified by documentation from the subject's primary care physician, and willing to defer vaccines through 6 months after completion of the subject's IM medication, or longer per Principal Investigator (PI) judgment. Emergency use authorization or conditional marketing authorization of coronavirus disease (COVID) vaccines is included unless there is an accepted medical exemption.
You may not qualify if:
- Inability to participate in the clinical evaluation as determined by PI
- Cohorts 1 to 3 only: Identification of two nonsense or null variants on genetic testing of the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)
- At least one S298P mutation in the SGSH gene (based upon review of documented results from a qualified laboratory, and with confirmation with Medical Monitor)
- Has evidence of an attenuated phenotype of MPS IIIA, in the judgement of the PI
- 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
- Cohorts 1 to 3 only: Subjects with total anti-AAV9 antibody titers ≥ 1:100 equivalent to a positive screen as determined by ELISA binding assay in serum
- Cohorts 1-3 only: Subjects with a positive response for the enzyme-linked immunosorbent spot assay (ELISpot) for T-cell responses to AAV9
- Cohorts 1-3 only: Serology consistent with exposure to human immunodeficiency virus (HIV), or serology consistent with active hepatitis B or C infection, Cohort 4: Current clinically significant infections (including any requiring systemic treatment including, but not limited to, HIV; hepatitis A, B, or C; varicella zosters virus; human T-cell lymphotropic virus type 1 \[HTLV-1\]; tuberculosis; or COVID-19) that would interfere with participation in the study.
- 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, hearing, or other impairment sufficient to preclude cooperation with neurodevelopmental testing
- Uncontrolled seizure disorder
- Any item (braces, etc.) or circumstance that 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
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Ultragenyx Pharmaceutical Inclead
- Abeona Therapeutics, Inccollaborator
Study Sites (5)
Nationwide Children's Hospital
Columbus, Ohio, 43205, United States
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224, United States
Women's and Children's Hospital
North Adelaide, South Australia, 5006, Australia
Vall d'Hebron Barcelona Hospital Campus
Barcelona, 08035, Spain
Hospital Clínico Universitario de Santiago
Santiago de Compostela, 15706, Spain
Related Publications (3)
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.
PMID: 27331076BACKGROUNDFu 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.
PMID: 29064732BACKGROUNDMcCurdy VJ, Johnson AK, Gray-Edwards HL, Randle AN, Bradbury AM, Morrison NE, Hwang M, Baker HJ, Cox NR, Sena-Esteves M, Martin DR. Therapeutic benefit after intracranial gene therapy delivered during the symptomatic stage in a feline model of Sandhoff disease. Gene Ther. 2021 Apr;28(3-4):142-154. doi: 10.1038/s41434-020-00190-1. Epub 2020 Sep 3.
PMID: 32884151DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
Medical Director
Ultragenyx Pharmaceutical Inc
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 17, 2016
First Posted
March 23, 2016
Study Start
April 25, 2016
Primary Completion (Estimated)
July 1, 2027
Study Completion (Estimated)
July 1, 2027
Last Updated
April 24, 2026
Record last verified: 2026-04
Data Sharing
- IPD Sharing
- Will not share