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

Study Overview
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Brief Summary
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This study is designed to assess the clinical benefit as well as the safety, pharmacokinetics (PK), and pharmacodynamics (PD) (reduction of galactitol levels) of AT-007 in pediatric subjects with Classic Galactosemia (CG).

Detailed Description
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This is a randomized, double-blind, placebo-controlled study in pediatric subjects with CG. Three age groups (≥2 to ≤6-year olds, ≥7 to ≤12-year olds, and ≥13 to <18- year olds) will be enrolled. The study is designed to assess the clinical benefit (changes in how pediatric patients with CG feels and function, changes in ocular disorders, and changes in sexual maturation, growth and development) as well as the safety, PK, and PD (reduction of galactitol levels) of AT-007 in pediatric subjects with CG. The study consists of 2 main parts, Part A and Part B, and an open-label extension (OLE). Part A is an intra-patient dose escalation evaluating multiple ascending doses (MAD) of AT-007. Part B is designed to assess the clinical benefits of long-term administration of AT-007 (at the optimum dose identified in Part A) on how patients with CG feel and function. Open-label extension (OLE) is an active treatment extension for patients who received placebo treatment in Part B.

Official Title
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A Sequential, Two-Part Study to Evaluate the Clinical Benefit, Safety, Pharmacokinetics, and Pharmacodynamic of AT-007 in Pediatric Subjects With Classic Galactosemia (CG)

Conditions
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Classic Galactosemia

Intervention / Treatment
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* Drug: AT-007
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion: Male Female non-pregnant Female non-lactating subjects aged ≥2 to <18 years. Diagnosis of Classic Galactosemia, confirmed by decreased GALT (galactose-1-phosphate uridyltransferase gut-associated lymphoid tissue )activity in erythrocytes, or a historical record of diagnosis of GALT (galactose-1-phosphate uridyltransferase gut-associated lymphoid tissue ) deficiency. Exclusion: Male/Female with no significant health problems (other than classic Galactosemia) No other disease that would preclude participation in the study.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: AT-007<br>AT-007 The starting dose in Part A will be 5 mg/kg for all age groups. For each age group, Part B of the study will not start until the optimum dose evaluated in Part A has been identified | Drug: AT-007<br>* Treatment with AT-007 given orally<br>* Other names: aldose reductase inhibitor;|
| Placebo Comparator: Placebo<br>Placebo given orally | Other: Placebo<br>* Placebo given orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institute of Health Toolbox Cognition Battery | NIH Toolbox Cognition Battery is a multiple of tests to show 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. | Every 6 months in Part B | 
| National Institute of Health Toolbox Motor Battery | NIH Toolbox Motor Battery is a multiple of tests to determine motor skills and is a comprehensive set of neuro-behavioral measurements that quickly assess cognitive, emotional, sensory, and motor functions from the convenience of an iPad. This is standardized normal or 100 with a standard deviation of 10. Higher scores are better. | Every 6 months in Part B | 
| Vineland Adaptive Behaviour Scales | Vineland Adaptive Behaviour Scales (Vineland-3) has a normal score of 100 and lower scores show developmental delay | Every 6 months in Part B | 
| Oral and Written Language Scales | Oral and Written Language Scales | Every 6 months in Part B | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Biomarker Measure | This biomarker measure will be performed to assess the inhibition of galactitol | Month 1- 3 in Part B | 
| Biomarker Analysis | This biomarker analysis will be performed to assess the levels of galactose and its other metabolites | Month 1 -3 in Part B | 
| Rate of Lens Opacity | 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. | Every 6 months in Part B | 
| Sexual maturation in female patients as indicated by Tanner Stage | 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. | Every 6 months in Part B | 
| Ovarian function in female patients determined by one hormonal test. | Ovarian function in female patients is recorded by hormonal measures which can be one of the following;FSH (follicle stimulating hormone), estradiol and/or LH (luteinizing hormone) | Every 6 months in Part B | 
| Spiral Drawing Test | Spiral Drawing Test is a multiple of tests showing drawing skills | Every 6 months in Part B | 
| Scale for Assessment & Rating of Ataxia | Scale for Assessment & Rating of Ataxia (SARA) is 0-40, the higher the score the worse value | Every 6 months in Part B | 
| Behavioral Assessment System for Children | Behavioral Assessment System for Children (BASC-3) has a normal range of 40 -060 with the higher score showing more difficulty. | Every 6 months in Part B | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Galactosemia, Classic Galactosemia