SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT02716246

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

Phase I/II Gene Transfer Clinical Trial of scAAV9.U1a.hSGSH for Mucopolysaccharidosis (MPS) IIIA

Open-label, dose-escalation clinical trial of scAAV9.U1a.hSGSH injected intravenously through a peripheral limb vein

NCT02716246 Mucopolysaccharidosis Type 3 A Sanfilippo Syndrome
MeSH: Mucopolysaccharidoses Mucopolysaccharidosis III

1 Interventions

Name: scAAV9.U1a.hSGSH

Description: Self-complementary adeno-associated virus serotype 9 carrying the human SGSH gene under the control of a U1a promoter (scAAV9.U1a.hSGSH) will be delivered one time through a venous catheter inserted into a peripheral limb vein.

Type: Biological

Cohort 1 Low Dose Cohort 2 Mid Dose Cohort 3 High Dose


Primary Outcomes

Description: 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 adverse events.

Measure: Product safety

Time: 24 months

Description: Change from baseline in the Age Equivalent Developmental Score calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, based on developmental age, compared with natural history study data at 6, 12, 18, and 24 months

Measure: Change from baseline in age equivalent developmental score

Time: 24 months

Secondary Outcomes

Description: Change from baseline of CSF heparan sulfate after treatment at 1, 6, 12, and 24 months

Measure: Change from baseline of CSF heparan sulfate after treatment

Time: 24 months

Description: Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment at Month 1, 6, 12, 18, 24

Measure: Change from baseline of plasma or urine glycosaminoglycans or heparan sulfate after treatment

Time: 24 months

Description: Change from baseline in CSF or plasma or leukocyte SGSH enzyme activity levels after treatment at Month 1, 6, 12, 24

Measure: Change from baseline in CSF or plasma or leukocyte SGSH enzyme activity levels after treatment

Time: 24 months

Description: Change from baseline in liver and/or spleen volumes after treatment as measured by MRI at Month 1, 6, 12, 24

Measure: Change from baseline in liver and/or spleen volumes after treatment

Time: 24 months

Description: Change from baseline in brain volume after treatment as measured by MRI at Month 1, 6, 12, 24

Measure: Change from baseline in brain volume after treatment

Time: 24 months

Description: Change from baseline in Cognitive Age Equivalent (Developmental Age) calculated using the Bayley Scales of Infant and Toddler Development or the Kaufman Assessment Battery for Children at Month 6, 12, 18, 24

Measure: Change from baseline in Cognitive Age Equivalent (Developmental Age)

Time: 24 months

Description: Change from baseline in 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 at Month 6, 12, 18, 24

Measure: Change from baseline in Adaptive Age Equivalent score

Time: 24 months

Description: Change from baseline Developmental Quotient after treatment compared to natural history study data assessed by Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, based on chronological and developmental age, at Month 6, 12, 18, 24

Measure: Change from baseline Developmental Quotient

Time: 24 months

Description: Change from baseline in the Sanfilippo Behavior Rating Scale at Month 6, 12, 18, 24

Measure: Change from baseline in the Sanfilippo Behavior Rating Scale

Time: 24 months

Description: Change from baseline in the Leiter-R at Month 6, 12, 18, 24

Measure: Change from baseline in the Leiter International Performance Scale - Revised

Time: 24 months

Description: Change from baseline in Pediatric Quality of Life Inventory (PedsQL) total score at Month 6, 12, 18, 24

Measure: Change from baseline in Pediatric Quality of Life Inventory (PedsQL) total score

Time: 24 months

Description: Change from baseline in parent quality of life, using the Parenting Stress Index, 4th ed (PSI-4) at Month 6, 12, 18, 24

Measure: Change from baseline in parent quality of life, using the Parenting Stress Index, 4th ed.

Time: 24 months

Description: Determination of vector shedding in plasma, saliva, urine, and feces to provide preliminary data for the Environmental Risk Assessment

Measure: Determination of vector shedding analysis

Time: 24 months

Purpose: Treatment

Allocation: Non-Randomized

Single Group Assignment


There is one SNP

SNPs


1 S298P

Inclusion Criteria: - Age 6 months to 2 years or children older than 2 years with a minimum cognitive Developmental Quotient (DQ) of 60 or above (calculated by Bayley Scales of Infant and Toddler Development - Third Edition) - Confirmed diagnosis of MPS IIIA by the following methods: - No detectable or significantly reduced* SGSH enzyme activity by leukocyte assay - Genomic DNA analysis demonstrating homozygous or compound heterozygous mutations in the SGSH gene Exclusion Criteria: - Inability to participate in the clinical evaluation as determined by PI - 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 - 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 patient from being able to undergo MRI according to local institutional policy - Any other situation that precludes the subject from undergoing any other procedure required in this study - Subjects with cardiomyopathy or significant congenital heart abnormalities - The presence of significant non-MPS IlIA 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 bhCG 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 - Due to the nature of enzyme activity testing, normal ranges and reported units vary from lab to lab. --- S298P ---



HPO Nodes