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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04902781
Recruitment Status : Active, not recruiting
First Posted : May 26, 2021
Last Update Posted : February 17, 2022
Sponsor:
Information provided by (Responsible Party):
Applied Therapeutics, Inc.

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).

Condition or disease Intervention/treatment Phase
Classic Galactosemia Drug: AT-007 Other: Placebo Phase 2 Phase 3

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.

A biomarker analysis will be performed at Month 1 - 3 to assess the inhibition of galactitol, as well as the levels of galactose and its other metabolites, safety and PK parameters.

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 47 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)
Actual Study Start Date : March 20, 2021
Estimated Primary Completion Date : April 2022
Estimated Study Completion Date : June 2023


Arm Intervention/treatment
Experimental: Experimental: AT-007
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
Treatment with AT-007 given orally
Other Name: aldose reductase inhibitor

Placebo Comparator: Placebo
Placebo given orally
Other: Placebo
Placebo given orally




Primary Outcome Measures :
  1. Biomarker Measure [ Time Frame: Month 1- 3 in Part B ]
    This biomarker measure will be performed to assess the inhibition of galactitol

  2. Biomarker Analysis [ Time Frame: Month 1 -3 in Part B ]
    This biomarker analysis will be performed to assess the levels of galactose and its other metabolites

  3. Oral and Written Language Scales [ Time Frame: Every 6 months in Part B ]
    Oral and Written Language Scales

  4. National Institute of Health Toolbox Cognition Battery [ Time Frame: Every 6 months in Part B ]
    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.

  5. National Institute of Health Toolbox Motor Battery [ Time Frame: Every 6 months in Part B ]
    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.

  6. Scale for Assessment & Rating of Ataxia [ Time Frame: Every 6 months in Part B ]
    Scale for Assessment & Rating of Ataxia (SARA) is 0-40, the higher the score the worse value

  7. Spiral Drawing Test [ Time Frame: Every 6 months in Part B ]
    Spiral Drawing Test is a multiple of tests showing drawing skills

  8. Bayley Scales of Infant and Toddler Development [ Time Frame: Every 6 months in Part B ]
    Bayley Scales of Infant and Toddler Development (Bayley-4) showing a score of 40 -160 with higher values showing more development.

  9. Behavioral Assessment System for Children [ Time Frame: Every 6 months in Part B ]
    Behavioral Assessment System for Children (BASC-3) has a normal range of 40 -060 with the higher score showing more difficulty.

  10. Vineland Adaptive Behaviour Scales [ Time Frame: Every 6 months in Part B ]
    Vineland Adaptive Behaviour Scales (Vineland-3) has a normal score of 100 and lower scores show developmental delay


Secondary Outcome Measures :
  1. Rate of Lens Opacity [ Time Frame: Every 6 months in Part B ]
    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.

  2. Sexual maturation in female patients as indicated by Tanner Stage [ Time Frame: Every 6 months in Part B ]
    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.

  3. Ovarian function in female patients determined by one hormonal test. [ Time Frame: Every 6 months in Part B ]
    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)



Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 17 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04902781


Locations
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United States, Colorado
Children's Hospital Colorado
Aurora, Colorado, United States, 80045
United States, Georgia
Rare Disease Research Center
Atlanta, Georgia, United States, 30318
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
Sponsors and Collaborators
Applied Therapeutics, Inc.
Investigators
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Study Chair: Susan E Waisbren, PhD Harvard University
Study Chair: Jonathan W Mink, MD University of Rochester
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Responsible Party: Applied Therapeutics, Inc.
ClinicalTrials.gov Identifier: NCT04902781    
Other Study ID Numbers: AT-007-1002
First Posted: May 26, 2021    Key Record Dates
Last Update Posted: February 17, 2022
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by Applied Therapeutics, Inc.:
Galactosemia
Classic Galactosemia
Additional relevant MeSH terms:
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Galactosemias
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Carbohydrate Metabolism, Inborn Errors
Metabolic Diseases