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

Applied Therapeutics, Inc.114 enrolled

Overview

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.

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

114

Conditions

Classic Galactosemia

Interventions

AT-007DRUG

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.

PlaceboDRUG

Matching placebo will be administered once in the morning before breakfast

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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).

Locations (4)

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, United States

Outcomes

Primary Outcomes

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.

Time frame: Events after 1 day of administration.

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.

Time frame: 7 Days after Dosing

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.

Time frame: 28 Days of Dosing

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.

Time frame: 90 Days after Dosing

Secondary Outcomes

Cmax of AT-007

Maximum (peak) plasma drug concentration

Time frame: 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

Data from ClinicalTrials.gov

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