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

Classic Galactosemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04902781
• Other study ID #: AT-007-1002
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: March 20, 2021
• Est. completion date: September 2023

Study information

• Verified date: February 2023
• Source: Applied Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 47
• Est. completion date: September 2023
• Est. primary completion date: April 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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.

Related Conditions & MeSH terms

• Classic Galactosemia
• Galactosemias

Intervention

Drug:
• AT-007
Treatment with AT-007 given orally

Other:
• Placebo
Placebo given orally

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Rare Disease Research Center	Atlanta	Georgia
United States	Children's Hospital Colorado	Aurora	Colorado

Sponsors (1)

Lead Sponsor	Collaborator
Applied Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Bayley Scales of Infant and Toddler Development	Bayley Scales of Infant and Toddler Development (Bayley-4) showing a score of 40 -160 with higher values showing more development. Exploratory Endpoint	Every 6 months in Part B
Primary	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
Primary	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
Primary	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
Primary	Oral and Written Language Scales	Oral and Written Language Scales	Every 6 months in Part B
Secondary	Biomarker Measure	This biomarker measure will be performed to assess the inhibition of galactitol	Month 1- 3 in Part B
Secondary	Biomarker Analysis	This biomarker analysis will be performed to assess the levels of galactose and its other metabolites	Month 1 -3 in Part B
Secondary	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
Secondary	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
Secondary	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
Secondary	Spiral Drawing Test	Spiral Drawing Test is a multiple of tests showing drawing skills	Every 6 months in Part B
Secondary	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
Secondary	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