MPS IIIAPhase 2/3NCT02716246
Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
A Phase 2/3 study testing UX111, Prophylactic Immunomodulatory (IM) Therapy and Optimized Prophylactic IM Therapy in people with MPS IIIA and Sanfilippo Syndrome, run by Ultragenyx Pharmaceutical Inc at 5 sites in 3 countries.
Trial summary
The main objective of this study is to evaluate the efficacy and safety of UX111 for the treatment of MPS IIIA. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- MPS IIIA, Sanfilippo Syndrome, Sanfilippo A
- What is being tested?
- UX111, Prophylactic Immunomodulatory (IM) Therapy and Optimized Prophylactic IM Therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 5 sitesin 3 countries
- Study dates
- 25 Apr 2016to Mar 2029
- Phase
- Phase 2/3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
- Cohort 4 only:
- 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.
Trial locations and contacts
5 sites in 3 countries. Contact the study team or a site near you to ask about taking part.
5 sites in 3 countries
United States2 sites
- Completed
Nationwide Children's Hospital
Columbus, Ohio, 43205
- Completed
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Spain2 sites, 2 recruiting
- Recruiting
Vall d'Hebron Barcelona Hospital Campus
Barcelona, Barcelona, 08035
Mireia del Toro, MD, mireia.deltoro@vallhebron.cat
Mireia del Toro, MD
- Recruiting
Hospital Clínico Universitario de Santiago
Santiago de Compostela, 15706
Eines Monteagudo, MD, eines.monteagudo.vilavedra@sergas.es
Beatriz Martín López-Pardo, MD, beatriz.martin.lopezpardo@sergas.es
Australia1 site
- Completed
Women's and Children's Hospital
North Adelaide, South Australia, 5006
About this study
Official title: Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA
The main objective of this study is to evaluate the efficacy and safety of UX111 for the treatment of MPS IIIA.
Read the detailed description
Open-label, single dose, dose-escalation clinical trial of UX111 (scAAV9.U1a.hSGSH) injected intravenously through a peripheral limb vein. A limited course of prophylactic immunomodulatory (IM) therapy will be administered. At approved sites adjuvant IM therapy may be administered to selected participants. 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.
This study was previously posted by Abeona Therapeutics, Inc and was transferred to Ultragenyx in August 2022.
- Conditions
- MPS IIIA, Sanfilippo Syndrome, Sanfilippo A, Mucopolysaccharidosis III
- Being tested
- UX111, Prophylactic Immunomodulatory (IM) Therapy, Optimized Prophylactic IM Therapy, Adjuvant IM Therapy
- Keywords
- MPS IIIA, Sanfilippo, Gene Therapy
- Medical subject headings
- Mucopolysaccharidosis III
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UX111Biological
Also called scAAV9.U1a.hSGSH, ABO-102, rebisufligene etisparvovec
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.
Prophylactic Immunomodulatory (IM) TherapyDrug
Optimized Prophylactic IM TherapyDrug
Adjuvant IM TherapyDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 Low Dose | Experimental | Dose of 0.5 X 10^13 vg/kg Receives: Biological: UX111; Drug: Prophylactic Immunomodulatory (IM) Therapy; Drug: Adjuvant IM Therapy |
| Cohort 2 Mid Dose | Experimental | Dose of 1 X 10^13 vg/kg Receives: Biological: UX111; Drug: Prophylactic Immunomodulatory (IM) Therapy; Drug: Adjuvant IM Therapy |
| Cohort 3 High Dose | Experimental | Dose of 3 X 10^13 vg/kg Receives: Biological: UX111; Drug: Prophylactic Immunomodulatory (IM) Therapy; Drug: Adjuvant IM Therapy |
| Cohort 4 High Dose (Spain Only) | Experimental | Dose of 3 X 10^13 vg/kg Receives: Biological: UX111; Drug: Optimized Prophylactic IM Therapy; Drug: Adjuvant IM Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to Month 24 Visit
Secondary outcomes (7)
Bayley Scales of Infant and Toddler Development-Third Edition (BSITD-III) Cognitive Raw Score Over Time
Measured: Up to Month 24 Visit
CSF Ganglioside Type 2 (GM2) Exposure
Exposure is defined as the time-normalized area under the curve (AUC) of the percentage change from baseline.
Measured: Up to Month 24 Visit
CSF Ganglioside Type 3 (GM3) Exposure
Exposure is defined as the time-normalized area under the curve (AUC) of the percentage change from baseline.
Measured: Up to Month 24 Visit
Percent Change from Baseline in CSF HS
Measured: Baseline, Up to Month 24 Visit
BSITD-III Receptive Communication Raw Score Over Time
Measured: Up to Month 24 Visit
BSITD-III Expressive Communication Raw Score Over Time
Measured: Up to Month 24 Visit
Percent Change From Baseline in Total Cortical Volume
Measured: Baseline, Up to Month 24 Visit
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2016 (estimated)
- Study start25 Apr 2016
- Primary completionMar 2029 (estimated)
- Study completionMar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for MPS IIIAStudies of the same condition, open and under way.
- More trials run by Ultragenyx Pharmaceutical IncThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ultragenyx Pharmaceutical Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Abeona Therapeutics, Inc
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Ultragenyx Pharmaceutical Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02716246
- Sponsor's protocol ID
- ABT-001
- Other IDs
- UX111-CL301, 2015-003904-21, 2023-510032-37-00, 2023, 2015
- Status last verified
- Sep 2026
- First submitted
- 17 Mar 2016
- Last updated
- 22 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
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.
PubMed 27331076Fu 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.
PubMed 29064732McCurdy 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.
PubMed 32884151