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Gene Transfer Clinical Trial for Mucopolysaccharidosis (MPS) IIIB (MPSIIIB)

This study is enrolling participants by invitation only.
Sponsor:
ClinicalTrials.gov Identifier:
NCT03315182
First Posted: October 20, 2017
Last Update Posted: November 6, 2017
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.
Collaborator:
Abeona Therapeutics, Inc
Information provided by (Responsible Party):
Kevin Flanigan, Nationwide Children's Hospital
October 10, 2017
October 20, 2017
November 6, 2017
October 16, 2017
October 2020   (Final data collection date for primary outcome measure)
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. [ Time Frame: 24 months ]
Same as current
Complete list of historical versions of study NCT03315182 on ClinicalTrials.gov Archive Site
  • Reduction from baseline values of glycosaminoglycans or their subunit, heparan sulfate, at 6 and/or 12 months after treatment, in any of the following: Cerebrospinal fluid, plasma or urine. [ Time Frame: 6 and/or 12 Months ]
  • Increase in CSF or plasma NAGLU enzyme activity levels at 6 and/or 12 months [ Time Frame: 6 and/or 12 months ]
  • Reduced liver and/or spleen volumes at 6 and/or 12 months after treatment, as measured by magnetic resonance imaging (MRI) [ Time Frame: 2 years ]
  • Attenuation of brain volume loss as measured by MRI in comparison to natural history data. [ Time Frame: 12 months ]
  • Improved adaptive functioning, or attenuation of decline in adaptive functioning as assessed by parent report using the Vineland Adaptive Behavior Scale [ Time Frame: 6 and/or 12 months ]
  • Improved cognitive ability or attenuation of cognitive deterioration as measured by direct testing of the child using the Leiter International Performance Scale, the Mullen Scales of Early Learning and/or the Sanfilippo Behavior Rating Scale. [ Time Frame: 6 and/or 12 months ]
Same as current
Not Provided
Not Provided
 
Gene Transfer Clinical Trial for Mucopolysaccharidosis (MPS) IIIB
Phase I/II Gene Transfer Clinical Trial of rAAV9.CMV.hNAGLU for Mucopolysaccharidosis (MPS) IIIB
Open-label, dose-escalation clinical trial of rAAV9.CMV.hNAGLU injected intravenously through a peripheral limb vein
Adeno-associated virus serotype 9 carrying the human NAGLU gene under the control of a CMV enhancer/promoter (rAAV9.CMV.hNAGLU) will be delivered one-time through a venous catheter inserted into a peripheral limb vein. The vector will be delivered undiluted over 10 to 20 minutes, under light to moderate sedation as needed. Dosing volume will be approximately 2-5 mL/kg, depending on final vector product concentration and subject cohort. A tapering course of prophylactic enteral prednisolone will be administered.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Intervention Model Description:
This is a dose escalation trial that will begin with the minimal efficacious dose as determined by preclinical studies and approved by the FDA. During the course of the trial, if safety is shown the dose will be escalated according to the clinical protocol.
Masking: None (Open Label)
Primary Purpose: Treatment
Mucopolysaccharidosis Type 3 B
Biological: rAAV9.CMV.hNAGLU
Adeno-associated virus serotype 9 carrying the human NAGLU gene under the control of a CMV enhancer/promoter (rAAV9.CMV.hNAGLU) will be delivered one-time through a venous catheter inserted into a peripheral limb vein. The vector will be delivered undiluted over 10 to 20 minutes, under light to moderate sedation as needed. Dosing volume will be approximately 2-5 mL/kg, depending on final vector product concentration and subject cohort. A tapering course of prophylactic enteral prednisolone will be administered.
  • Experimental: Cohort 1 (Low Dose) rAAV9.CMV.hNAGLU

    Subjects will receive a single infusion:

    • Cohort 1 (Low Dose): 2 X 10E13 vg/kg (n=3 subjects)

    Intervention: Biological: rAAV9.CMV.hNAGLU
  • Experimental: Cohort 2 (High Dose) rAAV9.CMV.hNAGLU

    Subjects will receive a single infusion:

    • Cohort 2 (High Dose): 5 X 10E13 vg/kg (n=3-6 subjects)

    Intervention: Biological: rAAV9.CMV.hNAGLU

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

Inclusion Criteria:

  • Age 2 years old or greater
  • Confirmed diagnosis of MPSIIIB by either of two methods:

    • No detectable or significantly reduced NaGlu enzyme activity by plasma, serum, or leukocyte assay.
    • Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the NAGLU gene
  • Clinical history or examination features of neurologic dysfunction

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 NAGLU gene, as judged by the principal investigator
  • Has evidence of an attenuated phenotype of MPS IIIB, as judged by the principal investigator
  • 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 ≥ 1:100 as determined by ELISA binding immunoassay
  • 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, 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 other situation that would exclude the patient from undergoing any other procedure required in this study
  • Patients with cardiomyopathy or significant congenital heart abnormalities
  • The presence of significant non-MPS IlIB related CNS impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study
  • Abnormal laboratory values based upon local institutional normal
  • Female participant who is pregnant or demonstrates a positive urine or Beta-hCG result at screening assessment (if applicable).
Sexes Eligible for Study: All
2 Years and older   (Child, Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States
 
 
NCT03315182
MPSIIIB
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Kevin Flanigan, Nationwide Children's Hospital
Kevin Flanigan
Abeona Therapeutics, Inc
Principal Investigator: Kevin Flanigan, MD Nationwide Children's Hospital
Nationwide Children's Hospital
November 2017

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