We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Try the New Site
We're building a modernized ClinicalTrials.gov! Visit Beta.ClinicalTrials.gov to try the new functionality.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03315182
Recruitment Status : Terminated (Abeona has decided to discontinue development activities for Product ABO-101 due to a lack of drug supply and for business reasons unrelated to the product safety profile and/or signs of efficacy)
First Posted : October 20, 2017
Last Update Posted : May 5, 2022
Sponsor:
Information provided by (Responsible Party):
Abeona Therapeutics, Inc

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
Open-label, dose-escalation clinical trial of rAAV9.CMV.hNAGLU injected intravenously through a peripheral limb vein

Condition or disease Intervention/treatment Phase
Mucopolysaccharidosis Type 3 B Biological: rAAV9.CMV.hNAGLU Phase 1 Phase 2

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 Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
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
Actual Study Start Date : October 16, 2017
Actual Primary Completion Date : April 7, 2022
Actual Study Completion Date : April 7, 2022

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
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)

 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.
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)

 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.
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)

 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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. 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 ]
  2. Product safety as defined by the incidence, type and severity of treatment-related adverse events and serious adverse events [ Time Frame: 24 Months ]

Secondary Outcome Measures :
  1. Change from baseline of central spinal fluid heparan sulfate after treatment [ Time Frame: 24 months ]
  2. Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment [ Time Frame: 24 Months ]
  3. Change from baseline in CSF or plasma NAGLU enzyme activity levels after treatment [ Time Frame: 24 Months ]
  4. Change from baseline in liver and/or spleen volumes after treatment, as measured by magnetic resonance imaging [ Time Frame: 24 Months ]
  5. Change from baseline in brain volumes after treatment, as measured by magnetic resonance imaging [ Time Frame: 24 Months ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. Change from baseline in Pediatric Quality of Life Inventory (PedsQL™) Generic Core Scales total score [ Time Frame: 24 Months ]
  10. Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4) short form [ Time Frame: 24 Months ]
  11. Determination of vector shedding analysis in plasma, saliva, urine and feces will provide preliminary data for the Environmental Risk Assessment [ Time Frame: 24 Months ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.


Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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
Layout table for location information
United States, Ohio
Nationwide Children's Hospital
Columbus, Ohio, United States, 43205
France
Armand-Trousseau Hospital
Paris, France
Germany
University Hospital Hamburg-Eppendorf
Hamburg, Germany
Spain
Hospital Clinico Universitario de Santiago
Santiago De Compostela, Spain, 15706
Sponsors and Collaborators
Abeona Therapeutics, Inc
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Layout table for additonal information
Responsible Party: Abeona Therapeutics, Inc
ClinicalTrials.gov Identifier: NCT03315182    
Other Study ID Numbers: ABT-002
First Posted: October 20, 2017    Key Record Dates
Last Update Posted: May 5, 2022
Last Verified: April 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share data

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Abeona Therapeutics, Inc:
MPS IIIB
Sanfilippo Syndrome B
Additional relevant MeSH terms:
Layout table for MeSH terms
Mucopolysaccharidoses
Mucopolysaccharidosis III
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
 Lysosomal Storage Diseases
Mucinoses
Connective Tissue Diseases
Metabolic Diseases