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

April 29, 2022 updated by: Abeona Therapeutics, Inc

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

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

11

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France
        • Armand-Trousseau Hospital
  • Germany
      • Hamburg, Germany
        • University Hospital Hamburg-Eppendorf
  • Spain
      • Santiago De Compostela, Spain, 15706
        • Hospital Clinico Universitario de Santiago
  • United States
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
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
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
24 Months

Secondary Outcome Measures

Outcome Measure
Time Frame
Change from baseline of central spinal fluid heparan sulfate after treatment
Time Frame: 24 months
24 months
Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment
Time Frame: 24 Months
24 Months
Change from baseline in CSF or plasma NAGLU enzyme activity levels after treatment
Time Frame: 24 Months
24 Months
Change from baseline in liver and/or spleen volumes after treatment, as measured by magnetic resonance imaging
Time Frame: 24 Months
24 Months
Change from baseline in brain volumes after treatment, as measured by magnetic resonance imaging
Time Frame: 24 Months
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
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
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
24 Months
Change from baseline in Pediatric Quality of Life Inventory (PedsQL™) Generic Core Scales total score
Time Frame: 24 Months
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
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
24 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Abeona Therapeutics, Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 16, 2017

Primary Completion (Actual)

April 7, 2022

Study Completion (Actual)

April 7, 2022

Study Registration Dates

First Submitted

October 10, 2017

First Submitted That Met QC Criteria

October 16, 2017

First Posted (Actual)

October 20, 2017

Study Record Updates

Last Update Posted (Actual)

May 5, 2022

Last Update Submitted That Met QC Criteria

April 29, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ABT-002

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

IPD Plan Description

There is no plan to share data

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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