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

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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

View this study on Beta.ClinicalTrials.gov

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

May 5, 2022

Actual Study Start Date ^ICMJE

October 16, 2017

Actual Primary Completion Date

April 7, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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

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

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

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

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

Terminated

Actual Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Actual Study Completion Date ^ICMJE

April 7, 2022

Actual Primary Completion Date

April 7, 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

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

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

Current Responsible Party

Abeona Therapeutics, Inc

Original Responsible Party

Kevin Flanigan, Nationwide Children's Hospital, Professor of Pediatrics

Current Study Sponsor ^ICMJE

Abeona Therapeutics, Inc

Original Study Sponsor ^ICMJE

Kevin Flanigan

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Not Provided

PRS Account

Abeona Therapeutics, Inc

Verification Date

April 2022

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

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