MPS IIIA, Mucopolysaccharidosis III, Sanfilippo A, Sanfilippo Syndrome
Conditions
Keywords
MPS IIIA, Sanfilippo, Gene therapy
Brief summary
Open-label, clinical trial of scAAV9.U1a.hSGSH injected intravenously through a peripheral limb vein
Detailed description
This is an open-label, single dose clinical trial. All participants will receive 3 X 10\^13 vg/kg of ABO-102 delivered one time through a venous catheter inserted into a peripheral limb vein. The target population includes MPS IIIA participants with a DQ lower than 60 in middle and advanced phases of the disease. Similar numbers of MPS IIIA participants with age equivalent above and below 18 months of age will be enrolled to ensure a representation of middle and advanced phases of the disease. This study was previously posted by Abeona Therapeutics, Inc and was transferred to Ultragenyx in August 2022.
Interventions
DRUGABO-102
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
Sponsors
Abeona Therapeutics, Inc
Ultragenyx Pharmaceutical Inc
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of MPS IIIA confirmed by the following methods: 1. 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 * Age range of 2 years up to 18 years (excluded)
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 v4.03 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 v4.03
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | From the first dose of study drug to <30 days postdose, Day 30, 60, 90, 180 and Month 12 | An adverse event (AE) is any untoward medical occurrence or unintended change from the time informed consent form (ICF) is signed, including inter-current illness that occurs during the course of a clinical trial after treatment has started, whether considered related to treatment or not. TEAEs are those that occurred after the start of study drug. Related adverse events were categorized as possible, probable, or definitely. |
| Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | From signing of informed consent through Day 60, 90, 180 and up to Day 454 (> 12 months) | An SAE is defined as any untoward medical occurrence that, at any dose: 1. Results in death 2. Is life threatening 3. Requires inpatient hospitalization or prolongation of existing hospitalization 4. Results in persistent disability/incapacity 5. Is a congenital anomaly/birth defect 6. Other situations such as important medical events that may not be immediately life threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. Relationship to study drug was defined as unrelated, unlikely, possible, probable, or definitely. |
| Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment | Baseline, Day 30, 180, Month 12 | As Measured by Magnetic Resonance Imaging (MRI). Baseline value of multiple of normal is calculated using the baseline values of the Liver volume/Spleen Volume/Height and Weight. * Body Surface Area (BSA) (m2)=( Height(cm) \* Weight (kg)/3600)1/2. * Normal Liver Volume=(689.9 \* BSA (m)) - 24.7. * Normal Spleen Volume (mL)=(4.6 \* Weight (kg)) + 0.7. * Liver Volume (multiples of normal)=Subject Liver Volume (mL)/Normal Liver Volume (mL). * Spleen Volume (multiples of normal)=Subject Spleen Volume (mL)/Normal Spleen Volume (mL). |
| Change From BL in Cerebrospinal Fluid (CSF) Heparan Sulfate Levels After Treatment | Baseline, Day 30, Day 180, Month 12 | Change from baseline in CSF heparan sulfate levels after treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Heparan N-Sulfatase (Type A) After Treatment | Baseline, Day 30, Day 180, Month 12 | — |
| Change From Baseline in Plasma SGSH After Treatment | Baseline, Day 30, Day 180, Month 12 | — |
| Change From Baseline in Brain Volumes After Treatment | Baseline, 12 months | As measured by MRI |
| Change From Baseline in Brain Volumes After Treatment: Average Total Cortical Thickness | Baseline, 12 months | As measured by MRI |
| Change From Baseline in Sleep Pattern as Measured by the Modified Children's Sleep Habits Questionnaire (CSHQ) Subscore Total After Treatment | Baseline, Day 180, Month 12 | CSHQ is a caregiver-completed, 35-item questionnaire that assesses the frequency of behaviors associated with common pediatric sleep difficulties. Eight domains of sleep, including Bedtime Resistance, Sleep Onset Delay, Sleep Duration, Sleep Anxiety, Night Awakenings, Parasomnias, Sleep Disordered Breathing, and Daytime Sleepiness are assessed, producing eight individual subdomain scores and an overall CSHQ subscore total. CSHQ total score is calculated by adding all the 8 subscores, and ranges from 36 to 108. A higher score is indicative of more disturbed sleep. |
| Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Core Generic Scales Total Score | Baseline, Day 180, Month 12 | PedsQL is a brief measure of health-related quality of life in children. The Peds QL Generic Core Scales was used in the study, consisting of 23 items applicable for healthy school and community populations, as well as pediatric populations with acute and chronic conditions. The four scales include Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. Item scores are added together and averaged to produce a Core total score, where higher scores on a scale of 0-100 indicate better Health-related Quality of Life (HRQOL). |
| Change From Baseline in Parent Quality of Life, Using the Parenting Stress Index, 4th Edition (PSI-4) Total Stress Raw Score | Baseline, Day 180, Month 12 | The Parenting Stress Index, 4th Edition evaluates the magnitude and type of stress in a parent/child relationship. The short form version was used in the study, consisting of 36 items divided into three domains: Parental Distress (PD), Parent-Child Dysfunctional Interaction (P-CDI), and Difficult Child (DC), which combine together to form a Total Stress raw score. Total Stress raw scores can range from 36 - 180, with higher raw scores indicating higher levels of stress. |
| Change From Baseline in Plasma Heparan Sulfate After Treatment | Baseline, Day 30, Day 180, Month 12 | — |
| Change From Baseline in Parent Global Impression (PGI) Total Score | Baseline, Day 180, Month 12 | The Parent Global Impression scale evaluates all aspects of a patients' health and assesses if there has been an improvement or decline in clinical status, as reported by the parent/caregiver. This study used a modified version with symptoms relevant to the patient population in the trial. Nine symptoms were scored at each visit, using a 7-point rating scale where 3 = much better, 2 = better, 1 = slightly better, 0 = same, -1 = slightly worse, -2 = worse, and -3 = much worse. The nine symptom scores are added together to produce a PGI total score, ranging from -27 to 27. |
| Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Day 180, Month 12 | The Clinical Global Impression of Improvement scale is a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication, specifically looking at whether the patient has demonstrated improvement or not. Assessment of improvement was scored at each visit, using a 7-point rating scale where 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse. |
| Change From Baseline in Parent Symptoms Score Questionnaire | Baseline, Day 180, Month 12 | The Parent Symptoms Score Questionnaire contains 29 symptoms with an indicator of whether the symptom was present or absent. |
| Percent Change From Baseline in Body Mass Index After Treatment | Baseline, Day 30, Day 180, Month 12 | — |
| Number of Participants With Abnormalities in Standard Awake 45-Minutes-Electroencephalogram (EEG) Monitoring at Baseline and Day 180 | Baseline, Day 180 | NCS=not clinically significant CS=clinically significant |
| Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Baseline, Day 30, Day 180, Month 12 | Detection of the adeno-associated Virus 9 (AAV9) viral deoxyribonucleic acid (DNA) in plasma, saliva, urine and feces was analyzed. Per protocol, data were not collected for urine at Month 12. |
| Change From Baseline in Gastrointestinal Symptoms Using the PedsQL™ Gastrointestinal (GI) Symptoms Scales Score | Baseline, Day 180, Month 12 | The PedsQL Gastrointestinal Symptoms Scale is a specific module of the PedsQL that measures gastrointestinal symptoms in patients with acute and chronic health conditions as well as healthy school and community populations. The Parent Report version was used on the study, consisting of 58 items across 10 dimensions, assessing parents' perceptions of their child's GI-specific symptoms. Item scores are added together and averaged to produce a GI symptoms scales score, where higher scores on a scale of 0-100 indicate better GI specific QOL. |
| Change From Baseline in Urine Glycosaminoglycans After Treatment | Baseline, Day 30, Day 180, Month 12 | — |
| Change From Baseline in Urine Heparan Sulfate After Treatment | Baseline, Day 30, Day 180, Month 12 | — |
| Change From Baseline in CSF N-Sulfoglucosamine Sulfohydrolase (SGSH) Enzyme Activity Levels After Treatment | Baseline, Day 30, Day 180, and Month 12 | — |
Countries
Australia, Spain, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg An intravenous injection of ABO-102 (scAAV9.U1a.hSGSH) via peripheral limb vein at a dose of 3.0 x 1013 vg/kg | 5 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other, Not Specified | 5 |
Baseline characteristics
| Characteristic | scAAV9.U1a.hSGSH, 3x1013 vg/kg |
|---|---|
| Age, Continuous | 69.02 months STANDARD_DEVIATION 34.692 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race/Ethnicity, Customized White | 5 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 5 |
| other Total, other adverse events | 5 / 5 |
| serious Total, serious adverse events | 3 / 5 |
Outcome results
Primary
Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment
As Measured by Magnetic Resonance Imaging (MRI). Baseline value of multiple of normal is calculated using the baseline values of the Liver volume/Spleen Volume/Height and Weight. * Body Surface Area (BSA) (m2)=( Height(cm) \* Weight (kg)/3600)1/2. * Normal Liver Volume=(689.9 \* BSA (m)) - 24.7. * Normal Spleen Volume (mL)=(4.6 \* Weight (kg)) + 0.7. * Liver Volume (multiples of normal)=Subject Liver Volume (mL)/Normal Liver Volume (mL). * Spleen Volume (multiples of normal)=Subject Spleen Volume (mL)/Normal Spleen Volume (mL).
Time frame: Baseline, Day 30, 180, Month 12
Population: Participants with an assessment at baseline and given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment | Liver volume: change from BL to Day 30 | -0.4200 ratio | Standard Deviation 0.08876 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment | Liver volume: change from BL to Day 180 | -0.4543 ratio | Standard Deviation 0.3156 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment | Liver volume: change from BL to Month 12 | -0.1765 ratio | Standard Deviation 0.17466 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment | Spleen volume: change from BL to Day 30 | -0.0603 ratio | Standard Deviation 0.19257 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment | Spleen volume: change from BL to Day 180 | -0.2253 ratio | Standard Deviation 0.53267 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline (BL) in Multiples of Normal of Liver and Spleen Volumes After Treatment | Spleen volume: change from BL to Month 12 | -0.1330 ratio | Standard Deviation 0.18102 |
Primary
Change From BL in Cerebrospinal Fluid (CSF) Heparan Sulfate Levels After Treatment
Change from baseline in CSF heparan sulfate levels after treatment
Time frame: Baseline, Day 30, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From BL in Cerebrospinal Fluid (CSF) Heparan Sulfate Levels After Treatment | Change from BL to Day 30 | -0.120 nmol/mL | Standard Deviation 0.0837 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From BL in Cerebrospinal Fluid (CSF) Heparan Sulfate Levels After Treatment | Change from BL to Day 180 | -0.183 nmol/mL | Standard Deviation 0.0289 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From BL in Cerebrospinal Fluid (CSF) Heparan Sulfate Levels After Treatment | Change from BL to Month 12 | -0.100 nmol/mL | — |
Primary
Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame
An adverse event (AE) is any untoward medical occurrence or unintended change from the time informed consent form (ICF) is signed, including inter-current illness that occurs during the course of a clinical trial after treatment has started, whether considered related to treatment or not. TEAEs are those that occurred after the start of study drug. Related adverse events were categorized as possible, probable, or definitely.
Time frame: From the first dose of study drug to <30 days postdose, Day 30, 60, 90, 180 and Month 12
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | < 30 days : Possible; Mild | 1 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | < 30 days : Possible; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | < 30 days : Possible; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | < 30 days : Probable; Mild | 2 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | < 30 days : Probable; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | < 30 days : Probable; Severe | 1 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | < 30 days : Definitely; Mild | 1 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | < 30 days : Definitely; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | < 30 days : Definitely; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 30 - < 60 days : Possible; Mild | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 30 - < 60 days : Possible; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 30 - < 60 days : Possible; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 30 - < 60 days : Probable; Mild | 2 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 30 - < 60 days : Probable; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 30 - < 60 days : Probable; Severe | 1 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 30 - < 60 days : Definitely; Mild | 1 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 30 - < 60 days : Definitely; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 30 - < 60 days : Definitely; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 60 - < 90 days : Possible; Mild | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 60 - < 90 days : Possible; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 60 - < 90 days : Possible; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 60 - < 90 days : Probable; Mild | 1 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 60 - < 90 days : Probable; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 60 - < 90 days : Probable; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 60 - < 90 days : Definitely; Mild | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 60 - < 90 days : Definitely; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 60 - < 90 days : Definitely; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 90 - < 180 days : Possible; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 90 - < 180 days : Possible; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 90 - < 180 days : Probable; Mild | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 90 - < 180 days : Probable; Moderate | 1 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 90 - < 180 days : Probable; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 90 - < 180 days : Definitely; Mild | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 90 - < 180 days : Definitely; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 90 - < 180 days : Definitely; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 180 - < 12 months : Possible; Mild | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 180 - < 12 months : Possible; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 180 - < 12 months : Possible; Severe | 1 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 180 - < 12 months : Probable; Mild | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 180 - < 12 months : Probable; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 180 - < 12 months : Probable; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 180 - < 12 months : Definitely; Mild | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 180 - < 12 months : Definitely; Moderate | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 180 - < 12 months : Definitely; Severe | 0 participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Related Treatment-Emergent Adverse Events (TEAEs) by Time Frame | 90 - < 180 days : Possible; Mild | 0 participants |
Primary
Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame
An SAE is defined as any untoward medical occurrence that, at any dose: 1. Results in death 2. Is life threatening 3. Requires inpatient hospitalization or prolongation of existing hospitalization 4. Results in persistent disability/incapacity 5. Is a congenital anomaly/birth defect 6. Other situations such as important medical events that may not be immediately life threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in the above definition. Relationship to study drug was defined as unrelated, unlikely, possible, probable, or definitely.
Time frame: From signing of informed consent through Day 60, 90, 180 and up to Day 454 (> 12 months)
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Unrelated; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Unrelated; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Unrelated; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Unlikely; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Unlikely; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Unlikely; Severe | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Possible; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Possible; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Possible; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Probable; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Probable; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Probable; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Definite; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Definite; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 60 - < 90 days : Definite; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Unrelated; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Unrelated; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Unrelated; Severe | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Unlikely; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Unlikely; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Unlikely; Severe | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Possible; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Possible; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Possible; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Probable; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Probable; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Probable; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Definite; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Definite; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 90 - < 180 days : Definite; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Unrelated; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Unrelated; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Unrelated; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Unlikely; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Unlikely; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Unlikely; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Possible; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Possible; Severe | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Probable; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Probable; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Probable; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Definite; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Definite; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Definite; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Unrelated; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Unrelated; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Unrelated; Severe | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Unlikely; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Unlikely; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Unlikely; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Possible; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Possible; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Possible; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Probable; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Probable; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Probable; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Definite; Moderate | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Definite; Severe | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | 180 days - < 12 months : Possible; Mild | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Incidence, Type and Severity of Serious Adverse Events (SAEs) by Time Frame | >= 12 months : Definite; Mild | 0 Participants |
Secondary
Change From Baseline in Brain Volumes After Treatment
As measured by MRI
Time frame: Baseline, 12 months
Population: Participants with an assessment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total cerebellar volume | -6.225 mL | Standard Deviation 11.2218 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total cerebral white matter volume | -6.385 mL | Standard Deviation 21.9698 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total gray matter volume | -153.190 mL | Standard Deviation 73.8927 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total intercranial volume | -122.245 mL | Standard Deviation 40.0576 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total white matter volume | -5.400 mL | Standard Deviation 25.9932 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in ventricular volumes | 34.165 mL | Standard Deviation 5.0417 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in amygdala volume | -0.635 mL | Standard Deviation 0.2333 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in corpus callosum volume | 0.285 mL | Standard Deviation 0.5445 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in CSF volume | 1.290 mL | Standard Deviation 0.5091 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total cerebellar gray matter volume | -7.210 mL | Standard Deviation 7.2125 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total cerebellar white matter volume | 0.985 mL | Standard Deviation 4.0234 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total brain volume | -157.705 mL | Standard Deviation 44.6114 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total cerebral volume | -152.365 mL | Standard Deviation 59.1353 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total cerebral gray matter volume | -145.975 mL | Standard Deviation 81.0981 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment | Change in total cortical volume | -144.170 mL | Standard Deviation 84.9235 |
Secondary
Change From Baseline in Brain Volumes After Treatment: Average Total Cortical Thickness
As measured by MRI
Time frame: Baseline, 12 months
Population: Participants with an assessment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Brain Volumes After Treatment: Average Total Cortical Thickness | -0.455 mm | Standard Deviation 0.2475 |
Secondary
Change From Baseline in CSF N-Sulfoglucosamine Sulfohydrolase (SGSH) Enzyme Activity Levels After Treatment
Time frame: Baseline, Day 30, Day 180, and Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in CSF N-Sulfoglucosamine Sulfohydrolase (SGSH) Enzyme Activity Levels After Treatment | Change from Baseline to Day 30 | 2.662 nmol/17 h/mL | Standard Deviation 5.9524 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in CSF N-Sulfoglucosamine Sulfohydrolase (SGSH) Enzyme Activity Levels After Treatment | Change from Baseline to Day 180 | -3.297 nmol/17 h/mL | Standard Deviation 5.71 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in CSF N-Sulfoglucosamine Sulfohydrolase (SGSH) Enzyme Activity Levels After Treatment | Change from Baseline to Month 12 | 0.000 nmol/17 h/mL | — |
Secondary
Change From Baseline in Gastrointestinal Symptoms Using the PedsQL™ Gastrointestinal (GI) Symptoms Scales Score
The PedsQL Gastrointestinal Symptoms Scale is a specific module of the PedsQL that measures gastrointestinal symptoms in patients with acute and chronic health conditions as well as healthy school and community populations. The Parent Report version was used on the study, consisting of 58 items across 10 dimensions, assessing parents' perceptions of their child's GI-specific symptoms. Item scores are added together and averaged to produce a GI symptoms scales score, where higher scores on a scale of 0-100 indicate better GI specific QOL.
Time frame: Baseline, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Gastrointestinal Symptoms Using the PedsQL™ Gastrointestinal (GI) Symptoms Scales Score | Change from Baseline to Day 180 | -5.88 score on a scale | Standard Deviation 9.261 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Gastrointestinal Symptoms Using the PedsQL™ Gastrointestinal (GI) Symptoms Scales Score | Change from Baseline to Month 12 | -4.15 score on a scale | Standard Deviation 6.01 |
Secondary
Change From Baseline in Heparan N-Sulfatase (Type A) After Treatment
Time frame: Baseline, Day 30, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Heparan N-Sulfatase (Type A) After Treatment | Change from Baseline to Day 30 | 0.578 nmol/17 h/mL | Standard Deviation 1.1299 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Heparan N-Sulfatase (Type A) After Treatment | Change from Baseline to Day 180 | 0.000 nmol/17 h/mL | Standard Deviation 0 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Heparan N-Sulfatase (Type A) After Treatment | Change from Baseline to Month 12 | 0.025 nmol/17 h/mL | Standard Deviation 0.0354 |
Secondary
Change From Baseline in Parent Global Impression (PGI) Total Score
The Parent Global Impression scale evaluates all aspects of a patients' health and assesses if there has been an improvement or decline in clinical status, as reported by the parent/caregiver. This study used a modified version with symptoms relevant to the patient population in the trial. Nine symptoms were scored at each visit, using a 7-point rating scale where 3 = much better, 2 = better, 1 = slightly better, 0 = same, -1 = slightly worse, -2 = worse, and -3 = much worse. The nine symptom scores are added together to produce a PGI total score, ranging from -27 to 27.
Time frame: Baseline, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Parent Global Impression (PGI) Total Score | Change at Day 180 | -3.0 score on a scale | Standard Deviation 6.48 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Parent Global Impression (PGI) Total Score | Change at Month 12 | -3.0 score on a scale | Standard Deviation 6.56 |
Secondary
Change From Baseline in Parent Quality of Life, Using the Parenting Stress Index, 4th Edition (PSI-4) Total Stress Raw Score
The Parenting Stress Index, 4th Edition evaluates the magnitude and type of stress in a parent/child relationship. The short form version was used in the study, consisting of 36 items divided into three domains: Parental Distress (PD), Parent-Child Dysfunctional Interaction (P-CDI), and Difficult Child (DC), which combine together to form a Total Stress raw score. Total Stress raw scores can range from 36 - 180, with higher raw scores indicating higher levels of stress.
Time frame: Baseline, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Parent Quality of Life, Using the Parenting Stress Index, 4th Edition (PSI-4) Total Stress Raw Score | Change from Baseline to Day 180 | -14.0 score on a scale | Standard Deviation 24.33 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Parent Quality of Life, Using the Parenting Stress Index, 4th Edition (PSI-4) Total Stress Raw Score | Change from Baseline to Month 12 | -9.0 score on a scale | Standard Deviation 4.24 |
Secondary
Change From Baseline in Parent Symptoms Score Questionnaire
The Parent Symptoms Score Questionnaire contains 29 symptoms with an indicator of whether the symptom was present or absent.
Time frame: Baseline, Day 180, Month 12
Population: Due to the inconsistent use of forms across visits and sites for this study, the data collected for this endpoint was incomplete, unreliable, and could not be evaluated.
Secondary
Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Core Generic Scales Total Score
PedsQL is a brief measure of health-related quality of life in children. The Peds QL Generic Core Scales was used in the study, consisting of 23 items applicable for healthy school and community populations, as well as pediatric populations with acute and chronic conditions. The four scales include Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. Item scores are added together and averaged to produce a Core total score, where higher scores on a scale of 0-100 indicate better Health-related Quality of Life (HRQOL).
Time frame: Baseline, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Core Generic Scales Total Score | Change from Baseline to Day 180 | -11.60 score on a scale | Standard Deviation 23.218 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Pediatric Quality of Life Inventory (PedsQL™) Core Generic Scales Total Score | Change from Baseline to Month 12 | -23.80 score on a scale | Standard Deviation 6.647 |
Secondary
Change From Baseline in Plasma Heparan Sulfate After Treatment
Time frame: Baseline, Day 30, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Plasma Heparan Sulfate After Treatment | Change from Baseline to Day 30 | -31.0 pmol/mL | Standard Deviation 9.62 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Plasma Heparan Sulfate After Treatment | Change from Baseline to Day 180 | -25.0 pmol/mL | Standard Deviation 7.07 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Plasma Heparan Sulfate After Treatment | Change from Baseline to Month 12 | -17.5 pmol/mL | Standard Deviation 17.68 |
Secondary
Change From Baseline in Plasma SGSH After Treatment
Time frame: Baseline, Day 30, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Plasma SGSH After Treatment | Change from Baseline to Day 30 | 6.50 nmol/17 h/mL | Standard Deviation 8.682 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Plasma SGSH After Treatment | Change from Baseline to Day 180 | 0.88 nmol/17 h/mL | Standard Deviation 1.825 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Plasma SGSH After Treatment | Change from Baseline to Month 12 | 0.05 nmol/17 h/mL | Standard Deviation 0.495 |
Secondary
Change From Baseline in Sleep Pattern as Measured by the Modified Children's Sleep Habits Questionnaire (CSHQ) Subscore Total After Treatment
CSHQ is a caregiver-completed, 35-item questionnaire that assesses the frequency of behaviors associated with common pediatric sleep difficulties. Eight domains of sleep, including Bedtime Resistance, Sleep Onset Delay, Sleep Duration, Sleep Anxiety, Night Awakenings, Parasomnias, Sleep Disordered Breathing, and Daytime Sleepiness are assessed, producing eight individual subdomain scores and an overall CSHQ subscore total. CSHQ total score is calculated by adding all the 8 subscores, and ranges from 36 to 108. A higher score is indicative of more disturbed sleep.
Time frame: Baseline, Day 180, Month 12
Population: participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Sleep Pattern as Measured by the Modified Children's Sleep Habits Questionnaire (CSHQ) Subscore Total After Treatment | Change from Baseline to Day 180 | 2.8 score on a scale | Standard Deviation 4.76 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Sleep Pattern as Measured by the Modified Children's Sleep Habits Questionnaire (CSHQ) Subscore Total After Treatment | Change from Baseline to Month 12 | 1.5 score on a scale | Standard Deviation 3.54 |
Secondary
Change From Baseline in Urine Glycosaminoglycans After Treatment
Time frame: Baseline, Day 30, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Urine Glycosaminoglycans After Treatment | Change from Baseline to Day 30 | -14.5 mg/mmol creatinine | Standard Deviation 9.33 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Urine Glycosaminoglycans After Treatment | Change from Baseline to Day 180 | -13.7 mg/mmol creatinine | Standard Deviation 9.81 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Urine Glycosaminoglycans After Treatment | Change from Baseline to Month 12 | -4.0 mg/mmol creatinine | — |
Secondary
Change From Baseline in Urine Heparan Sulfate After Treatment
Time frame: Baseline, Day 30, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Urine Heparan Sulfate After Treatment | Change from Baseline to Day 30 | -0.95 μmol/mmol creatinine | Standard Deviation 0.676 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Urine Heparan Sulfate After Treatment | Change from Baseline to Day 180 | -0.63 μmol/mmol creatinine | Standard Deviation 0.651 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Urine Heparan Sulfate After Treatment | Change from Baseline to Month 12 | 0.60 μmol/mmol creatinine | — |
Secondary
Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine
Detection of the adeno-associated Virus 9 (AAV9) viral deoxyribonucleic acid (DNA) in plasma, saliva, urine and feces was analyzed. Per protocol, data were not collected for urine at Month 12.
Time frame: Baseline, Day 30, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Plasma Change from Baseline to Day 30 | 45115.0 Copies per 1 mL of Specimen (copies/mL) | Standard Deviation 45413.33 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Plasma Change from Baseline to Day 180 | -2686.3 Copies per 1 mL of Specimen (copies/mL) | Standard Deviation 5372.5 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Plasma Change from Baseline to Month 12 | 2250.0 Copies per 1 mL of Specimen (copies/mL) | Standard Deviation 3181.98 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Saliva Change from Baseline to Day 30 | 17472.5 Copies per 1 mL of Specimen (copies/mL) | Standard Deviation 18345.89 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Saliva Change from Baseline to Day 180 | -1900.3 Copies per 1 mL of Specimen (copies/mL) | Standard Deviation 2330.09 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Saliva Change from Baseline to Month 12 | 0.0 Copies per 1 mL of Specimen (copies/mL) | — |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Stool Change from Baseline to Day 30 | -277522.5 Copies per 1 mL of Specimen (copies/mL) | Standard Deviation 760910.43 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Stool Change from Baseline to Day 180 | -800833.0 Copies per 1 mL of Specimen (copies/mL) | Standard Deviation 1132548.89 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Stool Change from Baseline to Month 12 | 0.0 Copies per 1 mL of Specimen (copies/mL) | — |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Urine Change from Baseline to Day 30 | 2250.0 Copies per 1 mL of Specimen (copies/mL) | Standard Deviation 2598.08 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Change From Baseline in Vector Shedding Analysis in Plasma, Saliva, Stool and Urine | Urine Change from Baseline to Day 180 | 1500.0 Copies per 1 mL of Specimen (copies/mL) | Standard Deviation 2598.08 |
Secondary
Clinical Global Impression Improvement Scale at Day 180 and Month 12
The Clinical Global Impression of Improvement scale is a brief, stand-alone assessment of the clinician's view of the patient's global functioning prior to and after initiating a study medication, specifically looking at whether the patient has demonstrated improvement or not. Assessment of improvement was scored at each visit, using a 7-point rating scale where 0 = not assessed, 1 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = very much worse.
Time frame: Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Day 180 | 0 = not assessed | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Day 180 | 1 = very much improved | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Day 180 | 2 = much improved | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Day 180 | 3 = minimally improved | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Day 180 | 4 = no change | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Day 180 | 5 = minimally worse | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Day 180 | 6 = much worse | 2 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Month 12 | 4 = no change | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Month 12 | 7 = very much worse | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Day 180 | 7 = very much worse | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Month 12 | 0 = not assessed | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Month 12 | 1 = very much improved | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Month 12 | 2 = much improved | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Month 12 | 3 = minimally improved | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Month 12 | 5 = minimally worse | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Clinical Global Impression Improvement Scale at Day 180 and Month 12 | Global Improvement, Month 12 | 6 = much worse | 2 Participants |
Secondary
Number of Participants With Abnormalities in Standard Awake 45-Minutes-Electroencephalogram (EEG) Monitoring at Baseline and Day 180
NCS=not clinically significant CS=clinically significant
Time frame: Baseline, Day 180
Population: Participants with an assessment
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Number of Participants With Abnormalities in Standard Awake 45-Minutes-Electroencephalogram (EEG) Monitoring at Baseline and Day 180 | Overall EEG : Baseline | Abnormal, CS | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Number of Participants With Abnormalities in Standard Awake 45-Minutes-Electroencephalogram (EEG) Monitoring at Baseline and Day 180 | Overall EEG : Baseline | Abnormal, NCS | 3 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Number of Participants With Abnormalities in Standard Awake 45-Minutes-Electroencephalogram (EEG) Monitoring at Baseline and Day 180 | Overall EEG : Baseline | Normal | 0 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Number of Participants With Abnormalities in Standard Awake 45-Minutes-Electroencephalogram (EEG) Monitoring at Baseline and Day 180 | Overall EEG : Day 180 | Abnormal, CS | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Number of Participants With Abnormalities in Standard Awake 45-Minutes-Electroencephalogram (EEG) Monitoring at Baseline and Day 180 | Overall EEG : Day 180 | Abnormal, NCS | 1 Participants |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Number of Participants With Abnormalities in Standard Awake 45-Minutes-Electroencephalogram (EEG) Monitoring at Baseline and Day 180 | Overall EEG : Day 180 | Normal | 1 Participants |
Secondary
Percent Change From Baseline in Body Mass Index After Treatment
Time frame: Baseline, Day 30, Day 180, Month 12
Population: Participants with an assessment at given time point
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Percent Change From Baseline in Body Mass Index After Treatment | Change from Baseline to Day 30 | -0.581 percent change | Standard Deviation 4.4477 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Percent Change From Baseline in Body Mass Index After Treatment | Change from Baseline to Day 180 | 3.875 percent change | Standard Deviation 9.0517 |
| scAAV9.U1a.hSGSH, 3x1013 vg/kg | Percent Change From Baseline in Body Mass Index After Treatment | Change from Baseline to Month 12 | 9.873 percent change | Standard Deviation 6.1672 |