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Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02716246
Recruitment Status : Active, not recruiting
First Posted : March 23, 2016
Last Update Posted : November 10, 2022
Sponsor:
Collaborator:
Abeona Therapeutics, Inc
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Description
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Brief Summary:
Open-label, dose-escalation clinical trial of scAAV9.U1a.hSGSH injected intravenously through a peripheral limb vein

Condition or disease Intervention/treatment Phase
MPS IIIA Sanfilippo Syndrome Sanfilippo A Mucopolysaccharidosis III Biological: ABO-102 Phase 1 Phase 2

Detailed Description:

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. A tapering course of prophylactic enteral prednisone or prednisolone will be administered for a period of at least two months.

This study was previously posted by Abeona Therapeutics, Inc and was transferred to Ultragenyx in August 2022.

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 28 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II/III Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA
Actual Study Start Date : March 2016
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1 Low Dose
Dose of 0.5 X 10^13 vg/kg
 Biological: ABO-102
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.
Other Names:
  • scAAV9.U1a.hSGSH
  • UX111
Experimental: Cohort 2 Mid Dose
Dose of 1 X 10^13 vg/kg
 Biological: ABO-102
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.
Other Names:
  • scAAV9.U1a.hSGSH
  • UX111
Experimental: Cohort 3 High Dose
Dose of 3 X 10^13 vg/kg
 Biological: ABO-102
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.
Other Names:
  • scAAV9.U1a.hSGSH
  • UX111


Outcome Measures
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Primary Outcome Measures :
  1. Product safety [ Time Frame: 24 months ]
    Determination of safety based on the development of unacceptable toxicity: defined as the occurrence of two or more unanticipated Grade III or higher treatment-related adverse events.

  2. Change from baseline in age equivalent developmental score [ Time Frame: 24 months ]
    Change from baseline in the Age Equivalent Developmental Score calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, based on developmental age, compared with natural history study data at 6, 12, 18, and 24 months


Secondary Outcome Measures :
  1. Change from baseline of CSF heparan sulfate after treatment [ Time Frame: 24 months ]
    Change from baseline of CSF heparan sulfate after treatment at 1, 6, 12, and 24 months

  2. Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment [ Time Frame: 24 months ]
    Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment at Month 1, 6, 12, 18, 24

  3. Change from baseline in CSF or plasma or leukocyte SGSH enzyme activity levels after treatment [ Time Frame: 24 months ]
    Change from baseline in CSF or plasma or leukocyte SGSH enzyme activity levels after treatment at Month 1, 6, 12, 24

  4. Change from baseline in liver and/or spleen volumes after treatment [ Time Frame: 24 months ]
    Change from baseline in liver and/or spleen volumes after treatment as measured by MRI at Month 1, 6, 12, 24

  5. Change from baseline in brain volume after treatment [ Time Frame: 24 months ]
    Change from baseline in brain volume after treatment as measured by MRI at Month 1, 6, 12, 24

  6. Change from baseline in Cognitive Age Equivalent (Developmental Age) [ Time Frame: 24 months ]
    Change from baseline in Cognitive Age Equivalent (Developmental Age) compared to natural history study calculated using the Bayley Scales of Infant and Toddler Development or the Kaufman Assessment Battery for Children at Month 6, 12, 18, 24

  7. Change from baseline in Adaptive Age Equivalent score [ Time Frame: 24 months ]
    Change from baseline in Adaptive Age Equivalent score after treatment compared to natural history study data, as assessed by parent report using the Vineland Adaptive Behavior Scale II Survey form at Month 6, 12, 18, 24

  8. Change from baseline Developmental Quotient [ Time Frame: 24 months ]
    Change from baseline Developmental Quotient after treatment compared to natural history study data assessed by Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, based on chronological and developmental age, at Month 6, 12, 18, 24

  9. Change from baseline in the Sanfilippo Behavior Rating Scale [ Time Frame: 24 months ]
    Change from baseline in the Sanfilippo Behavior Rating Scale at Month 6, 12, 18, 24

  10. Change from baseline in the Leiter International Performance Scale - Revised [ Time Frame: 24 months ]
    Change from baseline in the Leiter-R at Month 6, 12, 18, 24

  11. Change from baseline in Pediatric Quality of Life Inventory (PedsQL) total score [ Time Frame: 24 months ]
    Change from baseline in Pediatric Quality of Life Inventory (PedsQL) total score at Month 6, 12, 18, 24

  12. Change from baseline in parent quality of life, using the Parenting Stress Index, 4th ed. [ Time Frame: 24 months ]
    Change from baseline in parent quality of life, using the Parenting Stress Index, 4th ed short form (PSI-4) at Month 12, 24

  13. Determination of vector shedding analysis [ Time Frame: 24 months ]
    Determination of vector shedding in plasma, saliva, urine, and feces to provide preliminary data for the Environmental Risk Assessment


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Age: From birth to 2 years or children older than 2 years with a minimum cognitive Developmental Quotient (DO) of 60 or above (calculated by Bayley Scales of lnfant and Toddler Development - Third Edition)

Exclusion Criteria:

  • Inability to participate in the clinical evaluation as determined by PI
  • 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
  • Subjects with total anti-AAV9 antibody titers ≥ 1:100 as determined by ELISA binding immunoassay
  • Subjects 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
  • Uncontrolled seizure disorder
  • Any item (braces, etc.) which 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
  • Abnormal laboratory values Grade 2 or higher as defined in CTCAE v4.03 for GGT, total bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT and aPTT
  • Female participant who is pregnant or demonstrates a positive urine or bhCG 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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02716246


Locations
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United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
United States, Pennsylvania
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
Australia, South Australia
Women's and Children's Hospital
North Adelaide, South Australia, Australia, 5006
Spain
Vall d'Hebron Barcelona Hospital Campus
Barcelona, Spain, 08035
Hospital Clínico Universitario de Santiago
Santiago De Compostela, Spain, 15706
Sponsors and Collaborators
Ultragenyx Pharmaceutical Inc
Abeona Therapeutics, Inc
Investigators
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Study Director: Medical Director Ultragenyx Pharmaceutical Inc
More Information
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Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02716246    
Other Study ID Numbers: ABT001
UX111-CL301 ( Other Identifier: Ultragenyx Pharmaceutical Inc )
2015-003904-21 ( EudraCT Number )
First Posted: March 23, 2016    Key Record Dates
Last Update Posted: November 10, 2022
Last Verified: November 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share data

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Ultragenyx Pharmaceutical Inc:
MPS IIIA
Sanfilippo
Gene Therapy
Additional relevant MeSH terms:
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Mucopolysaccharidoses
Mucopolysaccharidosis III
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
 Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases