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

NCT ID: NCT04117711

Last Updated: 2024-05-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-21
• Study Completion Date: 2021-12-14

Brief 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.

Detailed 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).

Conditions

Classic Galactosemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

AT-007

AT-007 is a CNS and retina penetrant aldose reductase inhibitor.

Group Type: EXPERIMENTAL

AT-007

Intervention Type: DRUG

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 Comparator

Placebo is used as a comparator to the experimental arm.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matching placebo will be administered once in the morning before breakfast

Interventions

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.

Intervention Type: DRUG

Placebo

Matching placebo will be administered once in the morning before breakfast

Intervention Type: DRUG

Other Intervention Names

Govorestat

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Applied Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robert Green, MD, MPH

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

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

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AT-007-1001

Identifier Type: -

Identifier Source: org_study_id