Clinical Benefit, Safety, PK and PD Study of AT-007 in Pediatric Subjects With Classic Galactosemia

The primary endpoint is a GST of four components: 1) Behavioral Symptoms Index of the Behavioral Assessment Scale for Children 3 (BASC-3); 2) Activities of Daily Living from the BASC-3; 3) Oral Expression from the Oral and Written Language Skills-II (OWLS-II); 4) Listening Comprehension from the OWLS-II. Each individual component is also a secondary endpoint on their own with the test and scoring described below in the secondary endpoint section. For the GST, change from baseline using standardized z-scores is calculated for active versus placebo.

Sensitivity Analysis adding the National Institutes of Health Toolbox Cognition Battery (NIH-CB) test which measures cognition. NIH-CB is described below in the secondary endpoints. For the GST with cognition, change from baseline using standardized z-scores is calculated for active versus placebo.

Sensitivity Analysis adding the National Institutes of Health Toolbox Motor Battery (NIH-MB) 9-Hole Pegboard test which measures fine motor skills. NIH-MB is described below in the secondary endpoints. For the GST with fine motor skills, change from baseline using standardized z-scores is calculated for active versus placebo.

The change from baseline in plasma galactitol (Pharmacodynamic measure)

Behavioral Assessment System for Children (BASC-3) has a normal range of 40-60 with the higher score showing more difficulty. There are multiple outcome scores included such as: Behavioral Symptoms Index, Activities of Daily Living, Withdrawal, Adapatability, Adaptive Skills, Socialization, and Functional Impairment Index.

Change from baseline in the NIH Toolbox Cognition Battery (NIH-CB). The NIH-CB uses multiple tests to evaluate Cognition and consists of tests of multiple constructs to yield individual ranking and demonstrate Cognitive Function Composite, Fluid Cognition Composite Sequence Memory, List Sorting, Pattern Comparison, and Crystallized Cognition Composite, Picture Vocabulary and Reading Recognition. This is standardized normal or 100 with a standard deviation of 10. Higher scores are better.

The Archimedes Spiral Drawing Test evaluates tremor on a scale of 0 (no tremor) to 4 (severe tremor).

NIH Toolbox Motor Battery (NIH-MB) is a multiple of tests to determine fine motor skills using the 9-Hole Pegboard Test and gross motor skills using the Standing Balance Test. This is standardized normal or 100 with a standard deviation of 10. Higher scores are better.

Scale for Assessment & Rating of Ataxia (SARA) is 0-40, the higher the score the worse value

Oral and Written Language Scales-II (OWLS-II) has both an Oral Expression and Listening Comprehension score. Scores are 0-100 with a standard deviation of 15.

Onset and severity/progression of cataracts using the Lens Opacity System (LOCS) III, has a grading scale of 1-4, with 4 the most severe as assessed by the reviewer per standard criteria for anterior and posterior obstruction of the eye.

Sexual maturation in female patients as indicated by Tanner Stage 1- 4 which is the ranking of physical development in children, adolescents and adults. This defines physical measurements of development based on external primary and secondary sex characteristics, such as the size of the breasts, and development of pubic hair. This is assessed by physical exam with Stage 1 per-pubescent and Stage 4 post pubescent.

Ovarian function in female patients is recorded by hormonal measures: FSH (follicle stimulating hormone), estradiol, and LH (luteinizing hormone).

This biomarker analysis will be performed to assess the levels of galactose and its other metabolites; Exploratory Endpoint

Bayley Scales of Infant and Toddler Development (Bayley-4) showing a score of 40 -160 with higher values showing more development. Exploratory Endpoint

Vineland Adaptive Behavior Scales (Vineland-3) has a normal score of 100 and lower scores show developmental delay; Exploratory Endpoint