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

Primary Purpose

Classic Galactosemia

Status
Active
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
AT-007
Placebo
Sponsored by
Applied Therapeutics, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Classic Galactosemia focused on measuring Galactosemia, Classic Galactosemia

Eligibility Criteria

2 Years - 17 Years (Child)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Children's Hospital Colorado
  • Rare Disease Research Center
  • University of Michigan

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Experimental: AT-007

Placebo

Arm Description

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

Placebo given orally

Outcomes

Primary Outcome Measures

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.
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.
Vineland Adaptive Behaviour Scales
Vineland Adaptive Behaviour Scales (Vineland-3) has a normal score of 100 and lower scores show developmental delay
Oral and Written Language Scales
Oral and Written Language Scales

Secondary Outcome Measures

Biomarker Measure
This biomarker measure will be performed to assess the inhibition of galactitol
Biomarker Analysis
This biomarker analysis will be performed to assess the levels of galactose and its other metabolites
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.
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.
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)
Spiral Drawing Test
Spiral Drawing Test is a multiple of tests showing drawing skills
Scale for Assessment & Rating of Ataxia
Scale for Assessment & Rating of Ataxia (SARA) is 0-40, the higher the score the worse value
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.

Full Information

First Posted
July 14, 2020
Last Updated
February 22, 2023
Sponsor
Applied Therapeutics, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04902781
Brief Title
Clinical Benefit, Safety, PK and PD Study of AT-007 in Pediatric Subjects With Classic Galactosemia
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)
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 20, 2021 (Actual)
Primary Completion Date
April 2023 (Anticipated)
Study Completion Date
September 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Applied Therapeutics, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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).
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Classic Galactosemia
Keywords
Galactosemia, Classic Galactosemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Experimental: AT-007
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo given orally
Intervention Type
Drug
Intervention Name(s)
AT-007
Other Intervention Name(s)
aldose reductase inhibitor
Intervention Description
Treatment with AT-007 given orally
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo given orally
Primary Outcome Measure Information:
Title
National Institute of Health Toolbox Cognition Battery
Description
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.
Time Frame
Every 6 months in Part B
Title
National Institute of Health Toolbox Motor Battery
Description
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.
Time Frame
Every 6 months in Part B
Title
Vineland Adaptive Behaviour Scales
Description
Vineland Adaptive Behaviour Scales (Vineland-3) has a normal score of 100 and lower scores show developmental delay
Time Frame
Every 6 months in Part B
Title
Oral and Written Language Scales
Description
Oral and Written Language Scales
Time Frame
Every 6 months in Part B
Secondary Outcome Measure Information:
Title
Biomarker Measure
Description
This biomarker measure will be performed to assess the inhibition of galactitol
Time Frame
Month 1- 3 in Part B
Title
Biomarker Analysis
Description
This biomarker analysis will be performed to assess the levels of galactose and its other metabolites
Time Frame
Month 1 -3 in Part B
Title
Rate of Lens Opacity
Description
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.
Time Frame
Every 6 months in Part B
Title
Sexual maturation in female patients as indicated by Tanner Stage
Description
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.
Time Frame
Every 6 months in Part B
Title
Ovarian function in female patients determined by one hormonal test.
Description
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)
Time Frame
Every 6 months in Part B
Title
Spiral Drawing Test
Description
Spiral Drawing Test is a multiple of tests showing drawing skills
Time Frame
Every 6 months in Part B
Title
Scale for Assessment & Rating of Ataxia
Description
Scale for Assessment & Rating of Ataxia (SARA) is 0-40, the higher the score the worse value
Time Frame
Every 6 months in Part B
Title
Behavioral Assessment System for Children
Description
Behavioral Assessment System for Children (BASC-3) has a normal range of 40 -060 with the higher score showing more difficulty.
Time Frame
Every 6 months in Part B
Other Pre-specified Outcome Measures:
Title
Bayley Scales of Infant and Toddler Development
Description
Bayley Scales of Infant and Toddler Development (Bayley-4) showing a score of 40 -160 with higher values showing more development. Exploratory Endpoint
Time Frame
Every 6 months in Part B

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Susan E Waisbren, PhD
Organizational Affiliation
Harvard University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jonathan W Mink, MD
Organizational Affiliation
University of Rochester
Official's Role
Study Chair
Facility Information:
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Rare Disease Research Center
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30318
Country
United States
Facility Name
University of Michigan
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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

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