Functional correction of neurological and somatic disorders at later stages of disease in MPS IIIA mice by systemic scAAV9-hSGSH gene delivery.
Haiyan Fu, Marcela P Cataldi, Tierra A Ware...
https://pubmed.ncbi.nlm.nih.gov/27331076Actively Recruiting
Phase 2
Phase 3
All Genders
ID02716246
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis IIIA (Sanfilippo Syndrome)
Led by Ultragenyx Pharmaceutical Inc · Updated on 2026-04-24
36
Participants Needed
5
Research Sites
N/A
Total Duration
On this page
Sponsors
U
Ultragenyx Pharmaceutical Inc
Lead Sponsor
A
Abeona Therapeutics, Inc
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the safety and effectiveness of UX111, a gene transfer treatment, for individuals with Mucopolysaccharidosis IIIA (MPS IIIA), also known as Sanfilippo Syndrome. This open-label clinical trial includes dose escalation and aims to study how this treatment affects the disease. The study is sponsored by Ultragenyx Pharmaceutical Inc and includes participants from birth up to 5 years of age under specific cognitive development criteria. The treatment involves a single intravenous injection of UX111, a self-complementary adeno-associated virus serotype 9 carrying the human SGSH gene. Participants receive a limited course of prophylactic immunomodulatory therapy, with some possibly receiving additional adjuvant immunomodulatory therapy based on medical judgment. Four dosing cohorts are included, ranging from low to high doses, with one high-dose cohort specific to Spain. Participants will be closely monitored over up to 24 months through cognitive and developmental assessments, cerebrospinal fluid analyses measuring heparan sulfate and gangliosides, and brain volume measurements. Safety and response to treatment will be evaluated through laboratory tests and clinical observations. The study involves multiple visits including screening, treatment, and follow-up phases to assess the treatment's impact over time.
CONDITIONS
Brief Title
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
Who Can Participate
All Genders
Eligibility Criteria
You may qualify if you...
- Diagnosis of MPS IIIA confirmed by no or significantly reduced SGSH enzyme activity and genetic testing showing homozygous or compound heterozygous mutations in the SGSH gene
- Age from birth (USA and Australia) or 6 months (Spain) up to 2 years with no cognitive development quotient requirement, or older than 2 years with a cognitive development quotient of 60 or above
- Participants must be at least 6 months old before receiving UX111
- For Cohort 4 (Spain only): Age 3 months to 2 years with no cognitive quotient requirement, or older than 2 with cognitive quotient 60 or above; up to 2 subjects aged 2 to 5 years with cognitive quotient below 60 may be enrolled
- Vaccination status up to date according to country guidelines and willingness to defer vaccines through 6 months after immunomodulatory medication (Cohort 4 only)
You will not qualify if you...
- Inability to participate in clinical evaluation as determined by the principal investigator
- Identification of two nonsense or null variants in the SGSH gene (Cohorts 1 to 3 only)
- Presence of at least one S298P mutation in the SGSH gene
- Evidence of attenuated MPS IIIA phenotype
- Medical conditions preventing lumbar puncture or use of anesthetics
- Active viral infection or clinically significant infections that interfere with study participation
- Chronic illnesses or drug treatments posing risks for gene transfer or study procedures
- Positive anti-AAV9 antibody titers or T-cell responses against AAV9 (Cohorts 1 to 3 only)
- Positive serology for HIV or active hepatitis B or C infection (Cohorts 1 to 3 only)
- Bleeding disorders or contraindications to lumbar puncture
- Sensory impairments preventing cooperation with developmental testing
- Uncontrolled seizure disorder
- Conditions excluding MRI participation
- Cardiomyopathy or significant congenital heart abnormalities
- Significant CNS impairments or behavioral issues confounding study results
- Abnormal laboratory values as defined by study criteria
- Pregnancy or positive pregnancy test (females of childbearing potential)
- Recent vaccination with viral attenuated vaccines (Cohorts 1 to 3 only)
- Previous hematopoietic stem cell transplantation or gene/cell therapy or enzyme replacement therapy trial participation
- Known hypersensitivity or inability to avoid certain medications or substances interfering with immunomodulatory treatment (Cohort 4 only)
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
1
2
3
Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Treatment
Duration - Single dose with limited course of immunomodulatory therapy
Participants receive a single intravenous dose of UX111 through a venous catheter in a peripheral limb vein, along with a limited course of prophylactic immunomodulatory therapy. Some participants may also receive additional adjuvant immunomodulatory therapy based on clinical decisions.
1 dosing visit and multiple follow-up visits for immunomodulatory therapy
Follow-up
Duration - Up to 24 months
Participants are monitored for safety and treatment effects, including developmental assessments and cerebrospinal fluid analysis, for up to 24 months after dosing.
Periodic visits for assessments up to Month 24
Trial Site Locations
Total: 5 locations
1
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Completed
2
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
Completed
3
Women's and Children's Hospital
North Adelaide, South Australia, Australia, 5006
Completed
4
Vall d'Hebron Barcelona Hospital Campus
Barcelona, Spain, 08035
Actively Recruiting
5
Hospital Clínico Universitario de Santiago
Santiago de Compostela, Spain, 15706
Actively Recruiting
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Research Team
P
Patients Contact: Trial Recruitment
H
HCPs Contact: Medical Information
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NON_RANDOMIZED
Model
SEQUENTIAL
Primary Purpose
TREATMENT
Number of Arms
4
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Published Research Related To This Trial
Differential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy Children and Patients with Mucopolysaccharidosis III: Perspective for AAV-Mediated Gene Therapy.
Haiyan Fu, Aaron S Meadows, Ricardo J Pineda...
https://pubmed.ncbi.nlm.nih.gov/29064732Therapeutic benefit after intracranial gene therapy delivered during the symptomatic stage in a feline model of Sandhoff disease.
Victoria J McCurdy, Aime K Johnson, Heather L Gray-Edwards...
https://pubmed.ncbi.nlm.nih.gov/32884151