Gene Therapy Clinical Trial for Mucopolysaccharidosis IIIA in patient with middle and advanced phases of the disease

Phase 1

• Conditions: MPS IIIA is a devastating lysosomal storage disease, caused by a Nsulfoglucosamine sulfohydrolase gene defect. Infants with MPS IIIA appear normal at birth, but the disease is relentlessly progressive, withdeterioration 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 treatmentcurrently available for the disease.; MedDRA version: 20.1Level: PTClassification code 10056890Term: Mucopolysaccharidosis IIISystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2018-000504-42-ES
• Lead Sponsor: Abeona Therapeutics Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-04-09
• Last Update Posted: 9 May 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Diagnosis of MPS IIIA confirmed by the following methods:
o No detectable or significantly reduced SGSH enzyme activity by leukocyte assay, and
o Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the SGSH gene
• Cognitive Development Quotient (DQ) lower than 60 (calculated by Bayley Scales of Infant and Toddler Development - Third Edition)
• Must be ambulatory, though may receive assistance with ambulation
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 0
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

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 SGSH gene
• At least one S298P mutation in the SGSH gene
• Has evidence of an attenuated phenotype of MPS IIIA
• Presence of a concomitant medical condition that precludes lumbar puncture or use of anesthetics
• Active viral infection based on clinical observations
• 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
• Participants with total anti-AAV9 antibody titers = 1:100 as determined by ELISA binding immunoassay
• Participants 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
• Any item (braces, etc.) which would exclude the participant from being able to undergo MRI according to local institutional policy
• Any other situation that precludes the participant from undergoing procedures required in this study
• Participants with cardiomyopathy or significant congenital heart abnormalities
• The presence of significant non-MPS IIIA 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 (except in subjects diagnosed with Gilbert’s syndrome), creatinine, hemoglobin, WBC count, platelet count, PT and aPTT
• Female participant who is pregnant or demonstrates a positive urine or beta-hCG 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
• Participants who are anticipated to undergo a procedure involving anesthesia within 6 months post- drug administration
• Dysphagia present at Grade 3 or higher, as defined in CTCAE v4.0

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified