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

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03315182
Recruitment Status : Recruiting
First Posted : October 20, 2017
Last Update Posted : June 26, 2020
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 June 26, 2020
Actual Study Start Date  ICMJE October 16, 2017
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 9, 2019)
  • Change from baseline in the Age Equivalent Developmental score (calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children Second Edition, based on developmental age) compared with Natural History Study data [ Time Frame: 24 months ]
  • Product safety as defined by the incidence, type and severity of treatment-related adverse events and serious adverse events [ Time Frame: 24 Months ]
Original 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 27, 2020)
  • Change from baseline of central spinal fluid heparan sulfate after treatment [ Time Frame: 24 months ]
  • Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment [ Time Frame: 24 Months ]
  • Change from baseline in CSF or plasma NAGLU enzyme activity levels after treatment [ Time Frame: 24 Months ]
  • Change from baseline in liver and/or spleen volumes after treatment, as measured by magnetic resonance imaging [ Time Frame: 24 Months ]
  • Change from baseline in brain volumes after treatment, as measured by magnetic resonance imaging [ Time Frame: 24 Months ]
  • Change from baseline in the Cognitive Age Equivalent (Developmental Age) compared to Natural History Study, calculated using the Bayley Scales of Infant and Toddler Development or the Kaufman Assessment Battery for Children [ Time Frame: 24 Months ]
  • Change from baseline in the Adaptive Age Equivalent score after treatment compared to Natural History Study data, as assessed by parent report using the Vineland Adaptive Behavior Scale II Survey form [ Time Frame: 24 Months ]
  • Change from baseline Developmental Quotient after treatment compared to Natural History Study data assessed by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children. [ Time Frame: 24 Months ]
  • Change from baseline in Pediatric Quality of Life Inventory (PedsQL™) Generic Core Scales total score [ Time Frame: 24 Months ]
  • Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4) short form [ Time Frame: 24 Months ]
  • Determination of vector shedding analysis in plasma, saliva, urine and feces will provide preliminary data for the Environmental Risk Assessment [ Time Frame: 24 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. A tapering course of prophylactic enteral prednisone or prednisolone will be administered for a period of at least two months.
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.
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=2 participants)

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

    Subjects will receive a single infusion:

    • Cohort 2 (Med Dose): 5 X 10E13 vg/kg (n=4-5 participants)

    Intervention: Biological: rAAV9.CMV.hNAGLU
  • Experimental: Cohort 3 (High Dose) rAAV9.CMV.hNAGLU

    Subjects will receive a single infusion:

    • Cohort 3 (High Dose): 1 X 10E14 vg/kg (n=4-8 participants)

    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: April 27, 2020)
15
Original Estimated Enrollment  ICMJE
 (submitted: October 16, 2017)
9
Estimated Study Completion Date  ICMJE October 2022
Estimated Primary Completion Date October 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Confirmed diagnosis of MPSIIIB by both of the following two methods:

    • No detectable or significantly reduced NAGLU enzyme activity by plasma.
    • Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the NAGLU gene
  • Age: From Birth to 2 years or children older than 2 years with a minimum cognitive Development Quotient (DQ) of 60 or above (calculated by Bayley Scales of Infant and Toddler Development - Third Edition)

Exclusion Criteria:

  • Inability to participate in the clinical evaluation as determined by Principal Investigator
  • Identification of two nonsense or null variants on genetic testing of the NAGLU gene
  • Has evidence of an attenuated phenotype of MPS IIIB
  • Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
  • Active viral infection based on clinical observations as infections by Adenoviruses, Epstein-Barr Virus, Cytomegalovirus, Respiratory Syncytial Virus
  • Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer , or precludes the child from participating in the protocol assessments and follow up as autoimmune diseases requiring immunosuppression, such as juvenile rheumatoid arthritis or idiopathic thrombocytopenia purpura
  • Subjects with total anti-AAV9 antibody titers ≥ 1:100 as determined by ELISA binding immunoassay
  • Subjects with a positive response for the ELISPOT for T-cell responses to AAV9
  • 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
  • Any item (braces, etc.) which would exclude the subject from being able to undergo MRI according to local institutional policy
  • Any other situation that precludes the subject from undergoing procedures 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 serum result at screening assessment (if applicable).
  • Any vaccination with viral attenuated vaccines less than 30 days prior to the scheduled date of treatment (and use of prednisolone)
  • Previous treatment by Haematopoietic Stem Cell transplantation
  • Previous participation in a gene/cell therapy or ERT clinical trial
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Affairs +1 646 813 4701 sanfilippo@abeonatherapeutics.com
Listed Location Countries  ICMJE France,   Germany,   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 June 2020

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