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Trial record 1 of 2 for:    Abeona
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Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Abeona Therapeutics, Inc
Sponsor:
Information provided by (Responsible Party):
Abeona Therapeutics, Inc
ClinicalTrials.gov Identifier:
NCT02716246
First received: March 17, 2016
Last updated: August 17, 2017
Last verified: August 2017
  Purpose
Open-label, dose-escalation clinical trial of scAAV9.U1a.hSGSH injected intravenously through a peripheral limb vein

Condition Intervention Phase
Mucopolysaccharidosis Type 3 A Sanfilippo Syndrome Biological: scAAV9.U1a.hSGSH Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA

Resource links provided by NLM:


Further study details as provided by Abeona Therapeutics, Inc:

Primary Outcome Measures:
  • Development of unacceptable toxicity: [ 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 toxicity.


Secondary Outcome Measures:
  • Increase in CSF and blood leukocyte SGSH enzyme activity levels at 6 and/or 12 months [ Time Frame: 12 months ]
  • Reduced liver and spleen volumes at 6 and/or 12 months after treatment, as measured by magnetic resonance imaging (MRI) [ Time Frame: 12 months ]
  • Improved adaptive functioning, or arrest of decline in adaptive functioning at 6 and/or 12 months, as assessed by parent report using the Vineland Adaptive Behavior Scale [ Time Frame: 12 months ]
  • Improved cognitive ability or arrest of cognitive deterioration at 6 and/or 12 months after treatment, as measured by direct testing of the child using the Leiter International Performance Scale and the Mullen Scales of Early Learning [ Time Frame: 12 months ]
  • Reduction of urine glycosaminoglycans or heparan sulfate at 6 and/or 12 months after treatment [ Time Frame: 12 months ]

Estimated Enrollment: 9
Study Start Date: March 2016
Estimated Study Completion Date: December 2020
Estimated Primary Completion Date: December 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 Low Dose

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

• Cohort 1 (Low Dose): 5 X 10^12 vg/kg (n=3 subjects)

Biological: scAAV9.U1a.hSGSH
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.
Experimental: Cohort 2 High Dose

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

• Cohort 2 (High Dose): 1 X 10^13 vg/kg (n=3-6 subjects)

Biological: scAAV9.U1a.hSGSH
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.

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. The vector will be delivered undiluted approximately over 30 minutes, under light to moderate sedation as needed. Dosing volume will be approximately 0.5 to 1 mL/kg, depending on final vector product concentration and subject cohort. A tapering course of prophylactic enteral prednisone or prednisolone will be administered
  Eligibility

Ages Eligible for Study:   2 Years and older   (Child, Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 2 years old or greater
  • Confirmed diagnosis of MPS IIIA by either of two methods:
  • No detectable or significantly reduced* SGSH enzyme activity by leukocyte or fibroblast assay.
  • Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the SGSH gene
  • Clinical history or examination features of neurologic dysfunction

Exclusion Criteria:

  • Inability to participate in the clinical evaluation as determined by PI
  • Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
  • Inability to be safely sedated in the opinion of the clinical anesthesiologist
  • 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
  • Subjects with anti-AAV9 antibody titers ≥ 1:50 as determined by ELISA binding immunoassay
  • Serology consistent with exposure to HIV, or serology consistent with active hepatitis A, 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, due to the requirement for multiple MRI examinations as part of the study protocol. Subjects who are stable on anticonvulsive medications may be included
  • Any item (braces, etc.) which would exclude the patient from being able to undergo MRI according to local institutional policy
  • Any item (braces, etc.) which would exclude the patient from being able to undergo MRI according to local institutional policy
  • Patients 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, clinically significant laboratory values based upon normal values in the Nationwide Children's Hospital Laboratory as listed in Table 1 of the protocol.

    • Due to the nature of enzyme activity testing, normal ranges and reported units vary from lab to lab. Many laboratories utilize control samples rather than normal ranges, to account for the influence of small day-to-day fluctuations in the laboratory environment.
    • For the purposes of invitation to a screening visit, we will accept "significantly reduced" results as those interpreted as such by any clinical laboratory approved to perform this diagnostic test.

For uniformity of data for analysis, and confirmation of accurate diagnosis before gene transfer, subjects who consent to complete the screening visit will have their blood drawn for confirmatory enzyme activity level to be performed by Greenwood Genetics Center Biochemical Laboratory. Subjects must have an enzyme activity level considered to be in the affected range by Greenwood Genetic Center Biochemical Laboratory to proceed within the study.

  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02716246

Contacts
Contact: Krista Kunkler 614-722-2238 krista.kunkler@nationwidechildrens.org
Contact: Tabatha Simmons, PhD 614-722-6921 tabatha.simmons@nationwidechildrens.org

Locations
United States, Ohio
Nationwide Children's Hospital Recruiting
Columbus, Ohio, United States, 43205
Contact: Krista Kunkler    614-722-2238    krista.kunkler@nationwidechildrens.org   
Sponsors and Collaborators
Abeona Therapeutics, Inc
Investigators
Principal Investigator: Kevin Flanigan, MD Nationwide Children's Hospital
  More Information

Publications:
Responsible Party: Abeona Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT02716246     History of Changes
Other Study ID Numbers: ABT001
Study First Received: March 17, 2016
Last Updated: August 17, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share data

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Abeona Therapeutics, Inc:
MPS IIIA

Additional relevant MeSH terms:
Mucopolysaccharidoses
Mucopolysaccharidosis III
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases

ClinicalTrials.gov processed this record on September 19, 2017