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

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Disease Information

Descriptive Information
Brief Title † Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA
Official Title † Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH
Brief Summary Open-label, dose-escalation clinical trial of scAAV9.U1a.hSGSH injected intravenously through 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
Study Phase Phase 1/Phase 2
Study Type † Interventional
Study Design †
Primary Outcome Measure † Development of unacceptable toxicity:
Secondary Outcome Measure † Increase in CSF and blood leukocyte SGSH enzyme activity levels at 6 and/or 12 months
Condition † Mucopolysaccharidosis Type 3 A Sanfilippo Syndrome
Intervention † BiologicalscAAV9.U1a.hSGSH
Study Arms / Comparison Groups 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) 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)
Publications *

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information
Recruitment Status † Biological
Estimated Enrollment † 9
Start Date † March 2016
Completion Date December 2020
Primary Completion Date December 2019
Eligibility 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.
Gender All
Ages 2 Years - N/A
Accepts Healthy Volunteers No
Contacts †† Krista Kunkler, 614-722-2238, krista.kunkler@nationwidechildrens.org
Location Countries † United States
Administrative Information
NCT ID † NCT02716246
Organization ID MPS IIIA
Secondary IDs ††
Responsible Party Sponsor-Investigator
Study Sponsor † Kevin Flanigan
Collaborators †† Abeona Therapeutics
Investigators † Principal Investigator: Kevin Flanigan, MD, Nationwide Children's Hospital
Information Provided By
Verification Date February 2017
First Received Date † March 17, 2016
Last Updated Date February 6, 2017
† Required WHO trial registration data element.
†† WHO trial registration data element that is required only if it exists.
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