Gene Therapy for Sanfilippo Syndrome Type A (MPS IIIA)
This study is testing a gene therapy called UX111 (scAAV9.U1a.hSGSH) for Sanfilippo Syndrome Type A (MPS IIIA). UX111 is given once through a vein in your arm. The study also uses different types of immunomodulatory (IM) therapy, which are drugs given to help your body respond to the gene therapy. The main goal is to see how well UX111 works and if it's safe. Researchers will measure levels of a substance called Heparan Sulfate (HS) in your cerebrospinal fluid (the fluid around your brain and spinal cord) for up to 24 months to see if the treatment is successful. To join, you must have a confirmed diagnosis of MPS IIIA through specific enzyme and genetic tests. The study is currently unclear on its recruitment status and plans to enroll 36 participants.
- Study design
- This is an open-label, single-dose, dose-escalation study, meaning everyone knows what treatment is given, and the dose may increase for different groups of participants. It plans to enroll 36 participants.
- What's involved
- You would receive a one-time intravenous (into a vein) injection of UX111 and a limited course of prophylactic immunomodulatory therapy. Adjuvant immunomodulatory therapy may also be given if your doctor decides it's needed.
- Compensation
- Not stated in the trial record.
- Follow-up
- Researchers will measure a key marker in your cerebrospinal fluid for up to 24 months after treatment.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT02716246
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
Recruiting
PHASE2All AgesInterventionalTreatmentUltragenyx Pharmaceutical Inc
~36 participants
Updated 2026-08-21 on ClinicalTrials.gov
What's tested:UX111Prophylactic Immunomodulatory (IM) TherapyOptimized Prophylactic IM TherapyAdjuvant IM Therapy
At a glance
Recruiting sites
2 of 5 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Cerebrospinal Fluid (CSF) Heparan Sulfate (HS) (Disaccharide) Exposure
Measured over Up to Month 24 Visit
Conditions
Where it's being run
5 sites across 5 statesOhio1
Pennsylvania1
South Australia1
Barcelona1
Spain1
Study leadership
- Medical Director · STUDY_DIRECTOR · Ultragenyx Pharmaceutical Inc
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
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).
For Cohort 4 (participating sites in Spain): 3 months to ≤ 2 years of age with no BSITD-III Cognitive DQ requirement or \> 2 years of age with a BSITD-III Cognitive DQ ≥ 60 (n = up to 6). Up to 2 additional subjects \> 2 years and ≤ 5 years of age with a BSITD-III Cognitive DQ \< 60 may also be enrolled. •Subjects must be ≥ 6 months of age before UX111 administration. However, subjects may be consented and initiate relevant Screening Procedures and IM treatment \< 6 months of age. Refer to Section 8.2 for relevant screening procedures •For children ≤ 24 months chronological age who were born prematurely, defined as born at \< 36 weeks gestational age, the corrected gestational age must be used for determining inclusion •The BSITD-III Cognitive DQ is assessed during the onsite Screening visit, for subjects who require it •The age of the child on the date of the Screening BSITD-III assessment is used to determine the requirement for the BSITD-III Cognitive DQ score.
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.
Exclusion
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
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
Cohorts 1-3: Abnormal laboratory values Grade 2 or higher as defined in common terminology criteria for adverse events (CTCAE) v4.03 for gamma-glutamyl transferase (GGT), total bilirubin, creatinine, hemoglobin, white blood cell (WBC) count, platelet count, prothrombin time (PT) and activated partial thromboplastin time (aPTT), Cohort 4: Any of the following abnormal laboratory values from screening assessment:
Aspartate aminotransferase (AST), alanine aminotransferase (ALT), GGT, and/or alkaline phosphatase ≥ 2 × upper limit of normal (ULN) and/or total bilirubin \> 1.5 × ULN
Anemia (hemoglobin \< 10 g/dL)
Leukopenia or leukocytosis (total WBC count \< 3,000/mm3 and \> 15,000/mm3 respectively)
Abnormal absolute neutrophil count (ANC) of \< 1000/mm3
Platelet count \< 100,000/mm3
Coagulopathy (international normalized ratio \[INR\] \> 1.5) or aPTT \> 40 seconds
Renal impairment, defined as estimated glomerular filtration rate (eGFR) below the lower limit of normal (age and sex appropriate) based on Bedside Schwartz equation
Female of childbearing potential who is pregnant or demonstrates a positive urine or bhCG result at screening assessment (if applicable)
Cohorts 1-3: Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone)
Previous treatment by hematopoietic stem cell transplantation
Previous participation in a gene/cell therapy or enzyme replacement therapy (ERT) clinical trial
Known hypersensitivity, that in the judgment of the PI, places the subject at increased risk for adverse effects.
Unwilling to avoid consumption of grapefruit juice and the use of strong inhibitors of CYP3A4 and/or P-gp (eg, ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, or clarithromycin), strong inducers of CYP3A4 and/or P-gp (eg, rifampin, rifabutin, phenobarbital, carbamazepine, or phenytoin), and St. John's Wort from 30 days prior to Screening through completion of the IM regimen.
What this trial measures
- Cerebrospinal Fluid (CSF) Heparan Sulfate (HS) (Disaccharide) ExposureUp to Month 24 Visit
Exposure is defined as the time-normalized area under the curve (AUC) of the percentage reduction from baseline.