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

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ClinicalTrials.gov Identifier: NCT03315182
Recruitment Status : Recruiting
First Posted : October 20, 2017
Last Update Posted : January 31, 2019
Sponsor:
Information provided by (Responsible Party):
Abeona Therapeutics, Inc

Tracking Information
First Submitted Date  ICMJE October 10, 2017
First Posted Date  ICMJE October 20, 2017
Last Update Posted Date January 31, 2019
Actual Study Start Date  ICMJE October 16, 2017
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2017)
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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03315182 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: January 30, 2019)
  • 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: 6 and/or 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2017)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gene Transfer Clinical Trial for Mucopolysaccharidosis (MPS) IIIB
Official Title  ICMJE Phase I/II Gene Transfer Clinical Trial of rAAV9.CMV.hNAGLU for Mucopolysaccharidosis (MPS) IIIB
Brief Summary Open-label, dose-escalation clinical trial of rAAV9.CMV.hNAGLU injected intravenously through a peripheral limb vein
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE Mucopolysaccharidosis Type 3 B
Intervention  ICMJE 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 15 to 45 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.
Study Arms  ICMJE
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 16, 2017)
9
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE October 2020
Estimated Primary Completion Date October 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Age 6 months old or greater
  • Confirmed diagnosis of MPSIIIB by both of the following 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
  • Prior treatment with NAGLU enzyme replacement therapy (ERT)
  • 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 subject from being able to undergo MRI according to local institutional policy
  • Any other situation that would exclude the subject from undergoing any other procedure required in this study
  • Subjects 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 Grade 2 or higher as defined in CTCAE v4.0 for GGT, total bilirubin, creatinine, hemoglobin, WBC count, platelet count, PT, and aPTT
  • Female participant who is pregnant or demonstrates a positive urine or Beta-hCG result at screening assessment (if applicable).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 6 Months and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Juan Ruiz, MD +34 685895069 infotrials@abeonatherapeutics.com
Listed Location Countries  ICMJE Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03315182
Other Study ID Numbers  ICMJE ABT-002
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is no plan to share data
Responsible Party Abeona Therapeutics, Inc
Study Sponsor  ICMJE Abeona Therapeutics, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Abeona Therapeutics, Inc
Verification Date January 2019

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