Trial Outcomes & Findings for Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease (NCT NCT04088734)

Gene Transfer Study of ABO-102 in Patients With Middle and Advanced Phases of MPS IIIA Disease

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.

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.

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 baseline in CSF heparan sulfate levels after treatment

As measured by MRI

As measured by MRI

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.

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).

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.

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.

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.

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.

The Parent Symptoms Score Questionnaire contains 29 symptoms with an indicator of whether the symptom was present or absent.

NCS=not clinically significant CS=clinically significant

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.