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

• ClinicalTrials.gov Identifier: NCT05418829
• Recruitment Status: Active, not recruiting
• First Posted: June 14, 2022
• Last Update Posted: June 14, 2022
• Sponsor: Applied Therapeutics, Inc.
• Information provided by (Responsible Party): Applied Therapeutics, Inc.

Study Description

Brief Summary:

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.

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

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 7 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study to Evaluate the Long-Term Safety and Pharmacodynamic Efficacy of AT-007 in Adult Subjects With Classic Galactosemia (CG)
• Actual Study Start Date: October 1, 2021
• Estimated Primary Completion Date: November 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. 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 [ Time Frame: 12 months ]
2. To evaluate the pharmacokinetic (PK) parameter maximum concentration (Cmax) of 12-month oral administration of AT-007 in adult subjects with CG [ Time Frame: 12 months ]
   Maximum concentration will be determined by individual concentration time-data (mg/L)
3. 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) [ Time Frame: 12 months ]

Other Outcome Measures:

1. 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 [ Time Frame: 12 months ]
2. To evaluate the burden of illness (BOI) of adult subjects with CG- Medical History [ Time Frame: 12 months ]
   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)
3. To evaluate the burden of illness (BOI) of adult subjects with CG- NIH Motor Battery [ Time Frame: 12 months ]
   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.
4. To evaluate the burden of illness (BOI) of adult subjects with CG- Spiral Drawing Test [ Time Frame: 12 months ]
   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.
5. To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Emotional Distress questionnaire [ Time Frame: 12 months ]
   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]
6. To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Emotional Support questionnaire [ Time Frame: 12 months ]
   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]
7. To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Companionship questionnaire [ Time Frame: 12 months ]
   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]
8. To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Social Isolation questionnaire [ Time Frame: 12 months ]
   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]
9. To evaluate quality of life (QOL) measures of adult subjects with CG- PROMIS Ability to Participate in Social Roles and Activities questionnaire [ Time Frame: 12 months ]
   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]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, New Jersey

Hassman Research Institute

Berlin, New Jersey, United States, 08009

Sponsors and Collaborators

Applied Therapeutics, Inc.

More Information

• Responsible Party: Applied Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT05418829
• Other Study ID Numbers: AT-007-1006
• First Posted: June 14, 2022
• Last Update Posted: June 14, 2022
• Last Verified: June 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

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