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

NCT04117711 | Completed Phase 1 Results FDA Drug

• 1 other identifier: AT-007-1001
• Study Type: interventional
• Target: 114
• Locations: 1 country
• Sites: 4

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.

Conditions

Classic Galactosemia

Keywords

Classic Galactosemia; Aldose Reductase Inhibition; Galactose, Galactitol

Outcome Measures

Primary Outcomes (4)

• 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.

• 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

• 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

• 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 Outcomes (8)

• Cmax of AT-007

  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

• Tmax of AT-007

  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

• t1/2 of AT-007

  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.

• AUClast of AT-007

  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.

• AUCinf of AT-007

  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.

Study Arms (2)

AT-007

EXPERIMENTAL

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

Drug: AT-007

Placebo Comparator

PLACEBO COMPARATOR

Placebo is used as a comparator to the experimental arm.

Drug: Placebo

Interventions

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.

Also known as: Govorestat

AT-007

Placebo DRUG

Matching placebo will be administered once in the morning before breakfast

Placebo Comparator

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Applied Therapeutics, Inc.: lead

Study Sites (4)

Anaheim Clinical Trials, LLC

Anaheim, California, 92801, United States

Location

Atlanta Center for Medical Research

Atlanta, Georgia, 30331, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

ICON Clinical Research

San Antonio, Texas, 78209, United States

Location

MeSH Terms

Conditions

Galactosemias

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Riccardo Perfetti, MD
• Organization: Applied Therapeutics, Inc

rperfetti@appliedtherapeutics.com

2122209226

Study Officials

• Robert Green, MD, MPH

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2019
• First Posted: October 7, 2019
• Study Start: June 21, 2019
• Primary Completion: December 14, 2021
• Study Completion: December 14, 2021
• Last Updated: May 30, 2024
• Results First Posted: May 30, 2024

Record last verified: 2024-05

Locations

US (4)