Gene Therapy For Children With Variant Late Infantile Neuronal Ceroid Lipofuscinosis 6 (vLINCL6) Disease

An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic, or medical device (medicinal products). An SAE is an AE occurring during any study phase (for example, baseline, treatment, or follow-up) that fulfils any of the following: results in death; is life-threatening; requires inpatient hospitalization or prolongs existing hospitalization; results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; and results in a congenital anomaly/birth defect. All AEs that occurred after receipt of AT-GTX-501 are classified as TEAEs. A summary of serious and all other non-SAEs, regardless of causality, is located in the Reported Adverse Events module.

The Hamburg scale is an established tool to capture the rate of decline or regression. This tool was developed to document by rating motor, language, and visual functions in participants with late infantile neuronal ceroid lipofuscinosis type 2 (CLN2) Batten disease, and to collect their incidence of grand mal seizures. To assess disease progression and evaluate efficacy, the combined score of the motor and language domains of the Hamburg scale was used. Each domain was scored from 0 (no function) to 3 (normal function) for a maximal possible score of 6 for the combined score, referred to as the Hamburg Motor + Language aggregate score. The rate of decline in Hamburg Motor + Language aggregate, Motor, and Language scores were summarized using descriptive statistics.

The Unified Batten Disease Rating Scale (UBDRS) was developed to monitor rate of progression. This scale includes assessment of extrapyramidal movement abnormalities and seizures, behavioral and capability assessments (Actual Vision), as well as history relevant to variant late infantile neuronal ceroid lipofuscinosis associated with mutation(s) in the CLN6 gene (vLINCL6) disease and scoring for global impression of symptom severity. A higher UBDRS subscale score indicated greater physical impairment, with zero indicating a better outcome. Subscales included Physical Assessment (range 0-84), Seizure Assessment (range 0-54), Behavioral Assessment (range 0-55) and Capability Assessment of Actual Vision and Normal Vision (range 0-14). A positive change from baseline score indicates increased impairment and a negative score indicates decreased impairment.

The Mullen Scales of Early Learning were utilized to assess cognitive and motor ability in 4 areas (visual reception, fine motor, expressive language, and receptive language) in infants and children. Raw scores range from 0-50 for visual reception, 0-49 for fine motor, 0-50 for expressive language, and 0-48 for receptive language. Lower scores from baseline indicated increased developmental delay and higher scores from baseline indicated decreased developmental delay. A positive change from baseline score indicates decreased developmental delay and a negative score indicates increased developmental delay.

The Preschool Language Scales-5th Edition (PLS-5) (Age-Equivalent) was a comprehensive developmental language assessment. Standard scores from each domain (auditory comprehension, expressive communication, and total language) range from 50-150. Standard scores between 85 and 115 are considered to be within normal limits. Total scores are the sum of standard scores for auditory comprehension and expressive communication, which is then converted to a total standard score using PLS-5 Appendix B. Age-equivalent scores in each area were summarized by study visit with descriptive statistics. Higher scores represent better language development and lower scores reflect a possible language delay or disorder. A positive change from baseline score indicates better language development.

The Development Profile-3 was used to screen for developmental delays in 5 areas (physical [score range 0-35], adaptive behavior [0-37], social-emotional [0-36], cognitive [0-38], communication [0-34]), where lower scores indicated increased developmental delay. The General Development Score is obtained by adding the sum of standard scores for the five scales together (range 0-180). Standard Score ranges are <70 Delayed, 70-84 Below Average, 85-115 Average, 116-130 Above Average, and >130 Well Above Average. A positive change from baseline score indicates decreased developmental delay and a negative score indicates increased developmental delay.