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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04117711
Other study ID # AT-007-1001
Secondary ID
Status Completed
Phase Phase 1/Phase 2
First received
Last updated
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
Health authority
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).

Study Design


Related Conditions & MeSH terms


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.
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05418829 - AT-007 in Adult Subjects With Classic Galactosemia (CG) Phase 3
Enrolling by invitation NCT03838016 - Preventing Speech and Language Disorders in Children With Classic Galactosemia N/A
Active, not recruiting NCT04902781 - Clinical Benefit, Safety, PK and PD Study of AT-007 in Pediatric Subjects With Classic Galactosemia Phase 2/Phase 3
Completed NCT03580122 - The Effect of Arginine on Classic Galactosemia Phase 2