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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 : May 6, 2023
Sponsor:
Collaborator:
Abeona Therapeutics, Inc
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Description
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Brief Summary:
The main objective of this study is to evaluate the efficacy and safety of ABO-102 for the treatment of MPS IIIA.

Condition or disease Intervention/treatment Phase
MPS IIIA Sanfilippo Syndrome Sanfilippo A Mucopolysaccharidosis III Biological: ABO-102 Drug: Adjuvant Immunosuppression (IS) Therapy Phase 2 Phase 3

Detailed Description:

Open-label, single dose, dose-escalation clinical trial of ABO-102 (scAAV9.U1a.hSGSH) injected intravenously through a peripheral limb vein. A tapering course of prophylactic enteral prednisone or prednisolone will be administered for a period of at least three months. At approved sites immunosuppression (IS) 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 IS therapy. Not all participants may receive IS therapy.

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 : June 2024
Estimated Study Completion Date : June 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

Drug: Adjuvant Immunosuppression (IS) Therapy
The Principal Investigator and/or caregiver, in consultation with the medical monitor, will determine whether to initiate adjuvant IS therapy. Not all participants may receive IS therapy.
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

Drug: Adjuvant Immunosuppression (IS) Therapy
The Principal Investigator and/or caregiver, in consultation with the medical monitor, will determine whether to initiate adjuvant IS therapy. Not all participants may receive IS therapy.
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

Drug: Adjuvant Immunosuppression (IS) Therapy
The Principal Investigator and/or caregiver, in consultation with the medical monitor, will determine whether to initiate adjuvant IS therapy. Not all participants may receive IS therapy.


Outcome Measures
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Primary Outcome Measures :
  1. Change from Baseline in Cognitive Domain Bayley Scales of Infant and Toddler Development Raw Scores-Third edition (BSID-III) [ Time Frame: Baseline, Up to Month 24 ]
    If Applicable, According to the Appropriate Developmental Age, Non-verbal Index Raw Scores for Kaufman Assessment Battery for Children-Second Edition (KABC-II)


Secondary Outcome Measures :
  1. Change From Baseline in Vineland Adaptive Behavior Scale II-Survey Interview Form [ Time Frame: Baseline, Up to Month 24 ]
  2. Change From Baseline in Mullen Scales of Early Learning [ Time Frame: Baseline, Up to Month 24 ]
  3. Change From Baseline in BSID-III: Language Domain [ Time Frame: Baseline, Up to Month 24 ]
  4. Change From Baseline in BSID-III: Motor Domain [ Time Frame: Baseline, Up to Month 24 ]
  5. Change From Baseline in KABC-II, if Applicable [ Time Frame: Baseline, Up to Month 24 ]
    Subtests Required for the Fluid Crystallized Index Which are Common to all Age Brackets

  6. Change From baseline of Cerebrospinal Fluid (CSF) Heparan Sulfate After Treatment [ Time Frame: Baseline, Up to Month 24 ]
  7. Change From Baseline in CSF Gangliosides [GM2-GM3] [ Time Frame: Baseline, Up to Month 24 ]
  8. Change From Baseline in Brain Volumes After Treatment [ Time Frame: Baseline, Up to Month 24 ]

Other Outcome Measures:
  1. Number of Participants with Adverse Events, Treatment-emergent Adverse Events, and Serious Adverse Events [ Time Frame: Up to Month 24 ]

Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 (DQ) 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 Principal Investigator (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 equivalent to a positive screen as determined by ELISA in serum
  • Subjects with a positive response for the enzyme-linked immunosorbent spot (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 Hematopoietic Stem Cell transplantation
  • Previous participation in a gene/cell therapy or enzyme replacement therapy (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: May 6, 2023
Last Verified: May 2023
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