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Completed

NCT Number: NCT04117711

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

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.

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Key information

Conditions

Classic Galactosemia Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Carbohydrate Metabolism, Inborn Errors Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Galactosemias Genetic Diseases, Inborn Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases

Age range

18 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Anaheim Clinical Trials, LLC, Anaheim, California, United States

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About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

AT-007

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.

Other names: Govorestat

Placebo

Drug

Matching placebo will be administered once in the morning before breakfast

Primary outcomes

  1. Number of Participants With Treatment-emergent Adverse Events

    Time frame: Events after 1 day of administration.

    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.

  2. Number of Participants With Treatment-emergent Adverse Events

    Time frame: 7 Days after Dosing

    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.

  3. Number of Participants With Treatment-emergent Adverse Events

    Time frame: 28 Days of Dosing

    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.

  4. Number of Participants With Treatment-emergent Adverse Events

    Time frame: 90 Days after Dosing

    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.

Secondary outcomes

  1. Cmax of AT-007

    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

    Maximum (peak) plasma drug concentration

  2. Tmax of AT-007

    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

    Time to reach maximum (peak) plasma drug concentration

  3. t1/2 of AT-007

    Time frame: 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.

    Terminal elimination half life

  4. AUClast of AT-007

    Time frame: 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.

    Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration

  5. AUCinf of AT-007

    Time frame: 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.

    Area under the plasma concentration-time curve from time zero extrapolated to infinity

  6. Maximal Galactitol Reduction in Plasma

    Time frame: 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.

    Disease-Specific Biomarker in Classic Galactosemia Patients

  7. Galactose Concentration in Plasma

    Time frame: Part D: Day 32. Part D Extension: Days 30, 60, & 90.

    Disease-Specific Biomarker in Classic Galactosemia Patients

  8. Galactose-1-Phosphate (Gal-1p) Concentration in Plasma

    Time frame: Part D: Day 32. Part D Extension: Days 30, 60, & 90.

    Disease-Specific Biomarker in Classic Galactosemia Patients

Sponsors and collaborators

Lead sponsor

Applied Therapeutics, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Oct 7, 2019
Registry last updated
May 30, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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