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Report for Clinical Trial NCT04088734

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I/II Open Label, Single-dose, Gene Transfer Study of scAAV9.U1a.hSGSH (ABO-102) in Patients With Middle and Advanced Phases of MPS IIIA Disease

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

NCT04088734 MPS IIIA Sanfilippo Syndrome Sanfilippo A Mucopolysaccharidosis III
MeSH:Mucopolysaccharidoses Mucopolysaccharidosis III

1 Interventions

Name: ABO-102

Description: Single dose of ABO-102 (scAAV9.U1a.hSGSH) administered by intravenous injection through a peripheral limb vein at a dose of 3 X 10^13 vg/kg
Type: Drug
Group Labels: 1

ABO-102


Primary Outcomes

Description: The incidence, type, and severity of treatment-related adverse events and serious adverse events

Measure: Adverse Events and Serious Adverse Events

Time: 24 months

Description: Change from baseline in CSF heparan sulfate levels after treatment

Measure: CSF Heparan Sulfate

Time: 1, 6, 12, 24 months

Description: Change from baseline in liver and/or spleen volumes after treatment, as measured by MRI

Measure: Liver and/or Spleen Volumes

Time: 1, 6, 12, 24 months

Secondary Outcomes

Description: Change from baseline in plasma or urine glycosaminoglycans or heparan sulfate after treatment

Measure: Glycosaminoglycans or Heparan Sulfate

Time: 1, 6, 12, 18, 24 months

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

Measure: SGSH Enzyme Activity

Time: 1, 6, 12, 24 Months

Description: Change from baseline in brain volume after treatment, as measured by MRI

Measure: Brain Volume

Time: 1, 6, 12, 24 months

Description: Change from baseline in the Developmental Age after treatment compared to Natural History Study data calculated by the Mullen Scales of Early Learning or the Kaufman Assessment Battery for Children, 2nd edition, based on chronological and developmental age

Measure: Developmental Age

Time: 6, 12, 18, 24 months

Description: Change from baseline in the Cognitive Developmental Age after treatment compared to Natural History Study, calculated using the Bayley Scales of Infant and Toddler Development - Third edition or the Kaufman Assessment Battery for Children. Second Edition, based on developmental age

Measure: Cognitive Developmental Age

Time: 6, 12, 18, 24 months

Description: 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

Measure: Adaptive Age Equivalent Score

Time: 6, 12, 18, 24 months

Description: Change from baseline in the Sanfilippo Behavior Rating Scale

Measure: Sanfilippo Behavior Rating Scale

Time: 6, 12, 18, 24 months

Description: Change from baseline in sleep pattern as measured by the modified Children's Sleep Habits Questionnaire (CSHQ)

Measure: Sleep Pattern

Time: 6, 12, 18, 24 months

Description: Change from baseline in Pediatric Quality of Life Inventory (PedsQL™) Core Generic Scales total score

Measure: Pediatric Quality of Life Inventory

Time: 6, 12, 18, 24 months

Description: Change from baseline in parent quality of life, using the Parenting Stress Index, 4th Edition (PSI-4)

Measure: Parent Quality of Life

Time: 6, 12, 18, 24 months

Description: Change from baseline in gastrointestinal symptoms using the PedsQL™ Gastrointestinal Symptoms Scales

Measure: Gastrointestinal Symptoms

Time: 6, 12, 18, 24 months

Description: Change from baseline in Parent Global Impression Score

Measure: Parent Global Impression Score

Time: 6, 12, 18, 24 months

Description: Change from baseline in Clinical Global Impression Improvement Scale

Measure: Clinical Global Impression Improvement Scale

Time: 6, 12, 18, 24 months

Description: Change from baseline in Parent Symptoms Score Questionnaire

Measure: Parent Symptoms Score Questionnaire

Time: 6, 12, 18, 24 months

Description: Change from Baseline in Body Mass Index after treatment

Measure: Body Mass Index

Time: 6, 12, 18, 24 months

Description: Incidence and Change from baseline in abnormalities in standard awake 60-minutes- EEG monitoring

Measure: EEG Monitoring

Time: 6, 12, 18, 24 months

Description: Detection of the AAV9 viral DNA in plasma, saliva, urine and feces will be performed until two consecutive samples are negative

Measure: AAV9 Viral DNA Detection

Time: 24 months

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 S298P

No detectable or significantly reduced SGSH enzyme activity by leukocyte assay and 2. 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 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 greater than or equal to 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 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 (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 Inclusion Criteria: - Diagnosis of MPS IIIA confirmed by the following methods: 1. --- S298P ---

No detectable or significantly reduced SGSH enzyme activity by leukocyte assay and 2. 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 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 greater than or equal to 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 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 (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 MPS IIIA Sanfilippo Syndrome Sanfilippo A Mucopolysaccharidosis III Mucopolysaccharidoses Mucopolysaccharidosis III This is an open-label, single dose clinical trial. --- S298P ---



HPO Nodes