Gene transfer clinical trial for Mucopolysaccharidosis IIIB

• Register: EUCTR
• Last refreshed on: 6 December 2021
• Main ID: EUCTR2014-001411-39-ES
• Date of registration: 27/06/2018
• Prospective Registration: Yes
• Primary sponsor: Abeona Therapeutics Inc
• Public title: Gene transfer clinical trial for Mucopolysaccharidosis IIIB
• Scientific title: Phase I/II gene transfer clinical trial of rAAV9.CMV.hNAGLU for Mucopolysaccharidosis (MPS) IIIB
• Date of first enrolment: 04/09/2018
• Target sample size: 9
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2014-001411-39
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: yes; Other trial design description: Dose escalation; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

France, Germany, Italy, Netherlands, Spain, United Kingdom, United States

Contacts

• Name: Juan
• Affiliation: Abeona Therapeutics Inc

• Name: Juan
• Affiliation: Abeona Therapeutics Inc

Key inclusion & exclusion criteria

Inclusion criteria:
1. Age 6 months old or greater
2. Confirmed diagnosis of MPS IIIB by both of the following methods:
a. No detectable or significantly reduced NAGLU enzyme activity by plasma, serum, or leukocyte assay.
b. Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the NAGLU gene
3. Clinical history or examination features of neurologic dysfunction
Are the trial subjects under 18? yes
Number of subjects for this age range: 9
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Inability to participate in the clinical evaluation as determined by principal investigator
2. Identification of two nonsense or null variants on genetic testing of the NAGLU gene, as judged by the principal investigator
3. Prior treatment with NAGLU enzyme replacement therapy (ERT)
4. Has evidence of an attenuated phenotype of MPS IIIB, as judged by the principal investigator
5. Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
6. Inability to be safely sedated in the opinion of the clinical anesthesiologist
7. Active viral infection based on clinical observations
8. Concomitant illness or requirement for chronic drug treatment that in the opinion of the PI creates unnecessary risks for gene transfer
9. Subjects with anti-AAV9 antibody titers = 1:100 as determined by ELISA binding immunoassay
10. Serology consistent with exposure to HIV, or serology consistent with active hepatitis B or C infection
11. 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
12. Visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing
13. 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
14. Any item (braces, etc.) which would exclude the patient from being able to undergo MRI according to local institutional policy
15. Any other situation that would exclude the patient from undergoing any other procedure required in this study
16. Subjects with cardiomyopathy or significant congenital heart abnormalities
17. 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
18. 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
19. Female participant who is pregnant or demonstrates a positive urine or ?hCG result at screening assessment (if applicable).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

MPS IIIB is a devastating lysosomal storage disease, caused by a N-a-acetylglucosaminidase (NAGLU) gene defect. Infants with MPS IIIB appear normal at birth, but the disease is relentlessly progressive, with deterioration of social and adaptive abilities, neurocognitive decline, and premature death. Death typically occurs by end of the second or beginning of the third decade. Quite importantly, there is no treatment currently available for the disease.

Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Intervention(s)

Product Name: rAAV9.CMV.hNAGLU
Product Code: rAAV9.CMV.hNAGLU
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: rAAV9.CMV.hNAGLU
Current Sponsor code: rAAV9.CMV.hNAGLU
Other descriptive name: rAAV9.CMV.hNAGLU
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 50000000000000-

Primary Outcome(s)

Primary end point(s): Determination of safety: Adverse events and Serious Adverse events

Timepoint(s) of evaluation of this end point: Adverse events will be evaluated along the entire trial during 24 months

Main Objective: Determination of safety based on development of unacceptable toxicity

Secondary Objective: 1. Reduction of CSF, plasma or urine glycosaminoglycans or heparan sulfate at 6 and/or 12 months after treatment
2. Increase in CSF or plasma NAGLU enzyme activity levels at 6 and/or 12 months after treatment
3. Reduced liver and/or spleen volumes at 6 and/or 12 months after treatment, as measured by magnetic resonance imaging (MRI)
4. Improved adaptive functioning, or arrest of decline in adaptive functioning at 6 and/or 12 months after treatment, as assessed by parent report using the Vineland Adaptive Behavior Scale II
5. Improved cognitive ability or arrest of cognitive deterioration at 6 and/or 12 months after treatment, as measured by direct testing of the child using the Leiter International Performance Scale (brief IQ), the Mullen Scales of Early Learning; and by parent report using the Sanfilippo Behavior Rating Scale

Secondary Outcome(s)

Secondary end point(s): 1. Reduction of CSF, plasma or urine glycosaminoglycans or heparan sulfate at 6 and/or 12 months after treatment
2. Increase in CSF or plasma NAGLU enzyme activity levels at 6 and/or 12 months after treatment
3. Reduced liver and/or spleen volumes at 6 and/or 12 months after treatment, as measured by magnetic resonance imaging (MRI)
4. Improved adaptive functioning, or arrest of decline in adaptive functioning at 6 and/or 12 months after treatmnt, as assessed by parent report using appropiate scale.
5. Improved cognitive ability or arrest of cognitive deterioration at 6 and/or 12 months after treatment, as measured by direct testing of the child and by parent report using the appropiate scales.

Timepoint(s) of evaluation of this end point: - Day -45 to -1 (patient inclusion); day 1, 7, 14, 30, 60, 90, 180, month 12, month 18, month 24
- Day -45 to -1 (patient inclusion); day 7, 14, 30, 60, 90, 180, month 12, month 18, month 24
- Day -45 to -1 (patient inclusion); days 30, 180, month 12, month 24
- Day -45 to -1: day 180, month 12, month 18, month 24
- Day -45 to -1: day 180, month 12, month 18, month 24

Secondary ID(s)

ABT-002

ABO-101

Source(s) of Monetary Support

Abeona Therapeutics Inc

Ethics review

Status: Approved
Approval date: 01/08/2018
Contact: