We are updating the design of this site. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    NCT03315182
Previous Study | Return to List | Next Study

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
  Purpose
Open-label, dose-escalation clinical trial of rAAV9.CMV.hNAGLU injected intravenously through a peripheral limb vein

Condition Intervention Phase
Mucopolysaccharidosis Type 3 B Biological: rAAV9.CMV.hNAGLU Phase 1 Phase 2

Study Type: Interventional
Study Design: 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
Official Title: Phase I/II Gene Transfer Clinical Trial of rAAV9.CMV.hNAGLU for Mucopolysaccharidosis (MPS) IIIB

Resource links provided by NLM:


Further study details as provided by Kevin Flanigan, Nationwide Children's Hospital:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 9
Actual Study Start Date: October 16, 2017
Estimated Study Completion Date: October 2020
Estimated Primary Completion Date: October 2020 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)

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 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)

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.

Detailed Description:
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.
  Eligibility

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.


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 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).
  Contacts and Locations
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): NCT03315182


Locations
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
Sponsors and Collaborators
Kevin Flanigan
Abeona Therapeutics, Inc
Investigators
Principal Investigator: Kevin Flanigan, MD Nationwide Children's Hospital
  More Information

Publications:

Responsible Party: Kevin Flanigan, Professor of Pediatrics, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT03315182     History of Changes
Other Study ID Numbers: MPSIIIB
First Submitted: October 10, 2017
First Posted: October 20, 2017
Last Update Posted: November 6, 2017
Last Verified: November 2017

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

Keywords provided by Kevin Flanigan, Nationwide Children's Hospital:
MPS IIIB
Sanfilippo Syndrome B

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