Safety and Pharmacokinetics of AT-007 in Healthy Subjects and in Adult Subjects With Classic Galactosemia

Classic Galactosemia Clinical Trial

Official title:

A Phase 1-2, Dose-Escalating, 4-Part Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Doses of AT-007 in Healthy Adult Subjects and Adult Subjects With Classic Galactosemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04117711
• Other study ID #: AT-007-1001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: June 21, 2019
• Est. completion date: December 14, 2021

Study information

• Verified date: May 2024
• Source: Applied Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is a first-in-human, randomized, placebo-controlled, 4-Part, single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy adult subjects and adult subjects with Classic Galactosemia.

Description:

The study is designed to assess the safety and PK of AT-007 in healthy subjects and subjects with Classic Galactosemia as well as the effect of AT-007 on biomarkers of galactose metabolism (galactose, galactitol, and other galactose metabolites) in subjects with Classic Galactosemia.

This study consists of 4 parts:

• Part A (SAD) in 32 healthy subjects. Once daily oral escalating dose (6 active, 2 placebo).

• Part B and C (MAD for 7 days) in 36 healthy subjects. Once daily multiple daily dosing (8 active, 2 placebo per each dose cohort).

• Part D (SAD followed by MAD for 27 days) in 18 subjects with Classic Galactosemia. Once daily followed by multiple daily oral dosing (6 active, 2 placebo for each dose cohort).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 114
• Est. completion date: December 14, 2021
• Est. primary completion date: December 14, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Diagnosis of Classic Galactosemia confirmed by evidence of absent or significantly decreased (<1%) GALT activity in red blood cells and by GALT gene analysis

• Urine galactitol >100 mmol/mol creatinine

• Galactose-restricted diet

Exclusion Criteria:

• Complications of CG resulting in disability that, in the opinion of the Investigator, may prevent the subject from completing all study requirements (e.g., severe neurological deficits, severe cognitive impairment, or severe language difficulty).

• Renal disease (eGFR < 90 mL/min/1.73 m2 or albuminuria).

Related Conditions & MeSH terms

• Classic Galactosemia
• Galactosemias

Intervention

Drug:
• AT-007
AT-007 will be administered once daily before breakfast. Up to 4 different dose cohorts in part A; up to 4 dose cohorts in part B, up to 2 dose cohorts for part C, and up to 3 dose cohorts for part D will be enrolled in the study. The starting dose in Part A will be 0.5 mg/kg as a single dose. Subsequent doses in Part A and all doses in Parts B, C, and D will be based on the results of previous cohorts and/or previous parts of the study. Part B will start after all subjects in Part A have completed the study. Cohort C1 will be conducted simultaneously with Cohort B3 and using the same dose as Cohort B2. The dose for Cohort D1 will not be higher than the dose for Cohort B2. The second and third cohorts in Part D (D2 and D3) will not start until after all subjects in Cohorts B3 and B4, respectively, have completed the study and the dose levels will not be higher than those for Cohorts B3 and B4, respectively.
• Placebo
Matching placebo will be administered once in the morning before breakfast

Locations

Country	Name	City	State
United States	Anaheim Clinical Trials, LLC	Anaheim	California
United States	Atlanta Center for Medical Research	Atlanta	Georgia
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	ICON Clinical Research	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Applied Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-emergent Adverse Events	To evaluate the safety and tolerability of AT-007 after administration to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results.	Events after 1 day of administration.
Primary	Number of Participants With Treatment-emergent Adverse Events	To evaluate the safety and tolerability of AT-007 after multiple ascending doses are administered to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. Part B and Part C are combined.	7 Days after Dosing
Primary	Number of Participants With Treatment-emergent Adverse Events	To evaluate the safety and tolerability of AT-007 after multiple doses administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results.	28 Days of Dosing
Primary	Number of Participants With Treatment-emergent Adverse Events	To evaluate the safety and tolerability of AT-007 administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results.	90 Days after Dosing
Secondary	Cmax of AT-007	Maximum (peak) plasma drug concentration	Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs
Secondary	Tmax of AT-007	Time to reach maximum (peak) plasma drug concentration	Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs
Secondary	t1/2 of AT-007	Terminal elimination half life	Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part; predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours.
Secondary	AUClast of AT-007	Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration	Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours.
Secondary	AUCinf of AT-007	Area under the plasma concentration-time curve from time zero extrapolated to infinity	Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Part D: Determined using Day 1 with sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours.
Secondary	Maximal Galactitol Reduction in Plasma	Disease-Specific Biomarker in Classic Galactosemia Patients	Part D: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 12, 32. Part D Extension: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 30, 60, & 90.
Secondary	Galactose Concentration in Plasma	Disease-Specific Biomarker in Classic Galactosemia Patients	Part D: Day 32. Part D Extension: Days 30, 60, & 90.
Secondary	Galactose-1-Phosphate (Gal-1p) Concentration in Plasma	Disease-Specific Biomarker in Classic Galactosemia Patients	Part D: Day 32. Part D Extension: Days 30, 60, & 90.