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Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA

This study is currently recruiting participants.
See Contacts and Locations
Verified February 2017 by Kevin Flanigan, Nationwide Children's Hospital
Sponsor:
Collaborator:
Abeona Therapeutics, Inc
Information provided by (Responsible Party):
Kevin Flanigan, Nationwide Children's Hospital
ClinicalTrials.gov Identifier:
NCT02716246
First received: March 17, 2016
Last updated: February 6, 2017
Last verified: February 2017
March 17, 2016
February 6, 2017
March 2016
December 2019   (Final data collection date for primary outcome measure)
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.
Same as current
Complete list of historical versions of study NCT02716246 on ClinicalTrials.gov Archive Site
  • 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 ]
Same as current
Not Provided
Not Provided
 
Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA
Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
Open-label, dose-escalation clinical trial of scAAV9.U1a.hSGSH injected intravenously through a peripheral limb vein
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
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Mucopolysaccharidosis Type 3 A Sanfilippo Syndrome
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 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)

    Intervention: Biological: scAAV9.U1a.hSGSH
  • 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)

    Intervention: Biological: scAAV9.U1a.hSGSH
Duncan FJ, Naughton BJ, Zaraspe K, Murrey DA, Meadows AS, Clark KR, Newsom DE, White P, Fu H, McCarty DM. Broad functional correction of molecular impairments by systemic delivery of scAAVrh74-hSGSH gene delivery in MPS IIIA mice. Mol Ther. 2015 Apr;23(4):638-47. doi: 10.1038/mt.2015.9. Epub 2015 Jan 16.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
9
December 2020
December 2019   (Final data collection date for primary outcome measure)

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.

Sexes Eligible for Study: All
2 Years and older   (Child, Adult, Senior)
No
Contact: Krista Kunkler 614-722-2238 krista.kunkler@nationwidechildrens.org
Contact: Tabatha Simmons, PhD 614-722-6921 tabatha.simmons@nationwidechildrens.org
United States
 
 
NCT02716246
MPS IIIA
Yes
Not Provided
Plan to Share IPD: No
Plan Description: There is no plan to share data
Kevin Flanigan, Nationwide Children's Hospital
Kevin Flanigan
Abeona Therapeutics, Inc
Principal Investigator: Kevin Flanigan, MD Nationwide Children's Hospital
Nationwide Children's Hospital
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP