AT-007 in Adult Subjects With Classic Galactosemia (CG)

An Open-Label Study to Evaluate the Long-Term Safety and Pharmacodynamic Efficacy of AT-007 in Adult Subjects With Classic Galactosemia (CG)

This study is a 12-month open-label extension (OLE) study of AT-007 in adult subjects with CG who previously participated in Study AT-007-1001 Part D and/or Part D Extension.

The study is designed to assess the long-term safety of AT-007 in subjects with CG as well as the pharmacodynamics (PD) (inhibition of galactitol) and PK of AT-007. The effect of 12-month treatment with AT-007 on the levels of galactose and other galactose metabolites in subjects with CG will also be evaluated.

Study Overview

• Status: Active, not recruiting
• Conditions: Classic Galactosemia
• Intervention / Treatment: Drug: AT-007

Detailed Description

Primary:

- To evaluate the long-term safety of 12-month oral administration of AT-007 in adult subjects with Classic Galactosemia (CG)

Secondary:

• To evaluate the long-term inhibition of galactitol, a biomarker of aldose reductase (AR) activity, induced by 12-month oral administration of AT-007 to adult subjects with CG
• To evaluate the pharmacokinetic (PK) parameters of 12-month oral administration of AT-007 in adult subjects with CG

Exploratory:

• To evaluate the effect of 12-month oral administration of AT-007 on the levels of galactose and its other metabolites in adult subjects with CG
• To evaluate the burden of illness (BOI) of adult subjects with CG
• To evaluate quality of life (QOL) measures of adult subjects with CG
• To evaluate the effect of 12-month oral administration of AT-007 on the BOI and QOL of adult subjects with CG

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Hassman Research Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or non-pregnant, non-lactating female subject with a CG diagnosis
• Previous participation in Study AT-007-1001 Part D and/or Part D Extension
• No other significant health problems which preclude participation

Exclusion Criteria:

• Concomitant use of certain medications or over-the-counter therapies
• Discontinuation from Study AT-007-1001 Part D and/or Part D Extension due an adverse event

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AT-007; Open-label AT-007 20 mg/kg once daily	Drug: AT-007; AT-007 20 mg/kg once daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the long-term safety of 12-month oral administration of AT-007 in adult subjects with CG as assessed by adverse events.	Number of participants with treatment-emergent adverse events and broken down by organ class and relatedness.	12 months
To evaluate the long-term safety of 12-month oral administration of AT-007 in adult subjects with CG as assessed by clinical laboratory test results.	Number of participants with clinically-significant changes in clinical laboratory test results.	12 months
To evaluate the long-term safety of 12-month oral administration of AT-007 in adult subjects with CG as assessed by physical exam parameters.	Number of participants with clinically-significant changes in physical examination findings, vital sign abnormalities, and electrocardiogram findings.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the long-term change of galactitol, a biomarker of AR activity, induced by 12-month oral administration of AT-007 to adult subjects with CG		12 months
To evaluate the pharmacokinetic (PK) parameter maximum concentration (Cmax) of 12-month oral administration of AT-007 in adult subjects with CG	Maximum concentration will be determined by individual concentration time-data (mg/L)	12 months
To evaluate the pharmacokinetic (PK) parameter Area-Under-the-Curve (AUC) of 12-month oral administration of AT-007 in adult subjects with CG (mg*h/L)		12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the effect of 12-month oral administration of AT-007 on the levels of galactose and its other metabolites in adult subjects with CG		12 months
To evaluate the burden of illness (BOI) of adult subjects with CG- Medical History	Narrative description of natural course of CG as extracted by chart review and physical exam findings noted in chart review including the baseline neurologic exam upon entering the clinical trial. (There are no units for a descriptive narrative of medical history)	12 months
To evaluate the burden of illness (BOI) of adult subjects with CG- NIH Motor Battery	NIH Motor Battery produces normalized percentile scores with higher scores being more normal. As an exploratory endpoint, changes in the score from baseline to month 12 will assessed.	12 months
To evaluate the burden of illness (BOI) of adult subjects with CG- Spiral Drawing Test	Spiral Drawing Test produces normalized percentile scores with higher scores being more normal. As an exploratory endpoint, changes in the score from baseline to month 12 will assessed.	12 months
To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Emotional Distress questionnaire	The questionnaire assesses this function with higher scores relating to better function and may be used to compare over time for change from baseline to month 12. [PROMIS: Patient Reported Outcome Measure Information System]	12 months
To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Emotional Support questionnaire	The questionnaire assesses this function with higher scores relating to better function and may be used to compare over time for change from baseline to month 12. [PROMIS: Patient Reported Outcome Measure Information System]	12 months
To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Companionship questionnaire	The questionnaire assesses this function with higher scores relating to better function and may be used to compare over time for change from baseline to month 12. [PROMIS: Patient Reported Outcome Measure Information System]	12 months
To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Social Isolation questionnaire	The questionnaire assesses this function with higher scores relating to better function and may be used to compare over time for change from baseline to month 12. [PROMIS: Patient Reported Outcome Measure Information System]	12 months
To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Ability to Participate in Social Roles and Activities questionnaire	The questionnaire assesses this function with higher scores relating to better function and may be used to compare over time for change from baseline to month 12. [PROMIS: Patient Reported Outcome Measure Information System]	12 months

Collaborators and Investigators

• Sponsor: Applied Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): November 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: February 16, 2022
• First Submitted That Met QC Criteria: June 9, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Actual): June 14, 2022
• Last Update Submitted That Met QC Criteria: June 9, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Genetic Diseases, Inborn; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Brain Diseases, Metabolic; Brain Diseases, Metabolic, Inborn; Galactosemias
• Other Study ID Numbers: AT-007-1006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No