Clinical trial NCT04117711: Safety and Pharmacokinetics of AT-007 in Healthy Subjects and in Adult Subjects With Classic Galactosemia
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Classic Galactosemia
Keywords: Classic Galactosemia
Aldose Reductase Inhibition
Galactose, Galactitol
Lead sponsor: Applied Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2019-10-07
Enrollment: 114
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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).

Primary outcomes:
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: Events after 1 day of administration.
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: 7 Days after Dosing
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: 28 Days of Dosing
measure: Number of Participants With Treatment-emergent Adverse Events
timeFrame: 90 Days after Dosing
Secondary outcomes:
measure: Cmax of AT-007
timeFrame: 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
measure: Tmax of AT-007
timeFrame: 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
measure: t1/2 of AT-007
timeFrame: 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.
measure: AUClast of AT-007
timeFrame: 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.
measure: AUCinf of AT-007
timeFrame: 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.
measure: Maximal Galactitol Reduction in Plasma
timeFrame: 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.
measure: Galactose Concentration in Plasma
timeFrame: Part D: Day 32. Part D Extension: Days 30, 60, & 90.
measure: Galactose-1-Phosphate (Gal-1p) Concentration in Plasma
timeFrame: Part D: Day 32. Part D Extension: Days 30, 60, & 90.
Other outcomes:
Locations:
city: Anaheim
country: United States
facility: Anaheim Clinical Trials, LLC
state: California
city: Atlanta
country: United States
facility: Atlanta Center for Medical Research
state: Georgia
city: Boston
country: United States
facility: Brigham and Women's Hospital
state: Massachusetts
city: San Antonio
country: United States
facility: ICON Clinical Research
state: Texas
Study officials:
affiliation: Brigham and Women's Hospital
name: Robert Green, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: