Clinical trial NCT04902781: Clinical Benefit, Safety, PK and PD Study of AT-007 in Pediatric Subjects With Classic Galactosemia
Official title: A Sequential, Two-Part Study to Evaluate the Clinical Benefit, Safety, Pharmacokinetics, and Pharmacodynamics of AT-007 in Pediatric Patients With Classic Galactosemia (CG)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Classic Galactosemia
Keywords: Galactosemia
Classic Galactosemia
Lead sponsor: Applied Therapeutics, Inc.
Sponsor class: INDUSTRY
First posted: 2021-05-26
Enrollment: 47
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is designed to assess the clinical benefit as well as the safety, pharmacokinetics (PK), and pharmacodynamics (PD) (reduction of galactitol levels) of AT-007 in pediatric subjects with Classic Galactosemia (CG).

Detailed description: This is a randomized, double-blind, placebo-controlled study in pediatric subjects with CG. Children with CG ages 2 through 17 years will be enrolled. The study is designed to assess the clinical benefit using validated, standardized Clinical Outcome Assessments (COAs) as well as the safety, PK, and PD (reduction of galactitol levels) of AT-007 in pediatric subjects with CG. The study consists of 2 main parts, Part A and Part B, and an open-label extension (OLE).

Part A is an intra-patient dose escalation evaluating multiple ascending doses (MAD) of AT-007.

Part B is designed to assess the clinical benefits of long-term administration of AT-007 (at the optimum dose identified in Part A) on validated, standardized COAs.

Open-label extension (OLE) is an active treatment extension for patients who received placebo treatment in Part B.

Eligibility criteria: Inclusion:

* Male
* Female non-pregnant
* Female non-lactating subjects aged ≥2 to \<18 years.
* Diagnosis of Classic Galactosemia, confirmed by \<1% GALT (galactose-1-phosphate uridyltransferase) enzyme activity in erythrocytes, or a historical record of diagnosis of \<1% GALT enzyme activity.

Exclusion:

* Male/Female with no significant health problems (other than classic Galactosemia)
* No other disease that would preclude participation in the study.

Primary outcomes:
measure: Global Statistical Test (GST)
timeFrame: Month 6, Month 12 and Month 18
measure: Sensitivity Analysis of the Primary Endpoint (GST) with Cognition
timeFrame: Month 6, Month 12 and Month 18
measure: Sensitivity Analysis of the Primary Endpoint (GST) with Fine Motor Skills
timeFrame: Month 6, Month 12 and Month 18
Secondary outcomes:
measure: Galactitol Level
timeFrame: Month 1, Month 2, Month 3, Month 6, Month 12, and Month 18
measure: Behavioral Assessment System for Children-3 [Individual Components]
timeFrame: Month 6, Month 12 and Month 18
measure: National Institute of Health Toolbox Cognition Battery
timeFrame: Month 6, Month 12 and Month 18
measure: Archimedes Spiral Drawing Test
timeFrame: Month 6, Month 12 and Month 18
measure: National Institute of Health Toolbox Motor Battery
timeFrame: Month 6, Month 12 and Month 18
measure: Scale for Assessment & Rating of Ataxia
timeFrame: Month 6, Month 12 and Month 18
measure: Oral and Written Language Scales-II
timeFrame: Month 6, Month 12 and Month 18
measure: Rate of Lens Opacity
timeFrame: Month 6, Month 12 and Month 18
measure: Sexual maturation in female patients as indicated by Tanner Stage
timeFrame: Month 6, Month 12 and Month 18
measure: Ovarian function in female patients determined by hormonal tests.
timeFrame: Month 6, Month 12 and Month 18
Other outcomes:
measure: Biomarker Analysis [Exploratory]
timeFrame: Month 1, Month 2, Month 3, Month 6, Month 12, and Month 18
measure: Bayley Scales of Infant and Toddler Development-4 [Exploratory]
timeFrame: Month 6, Month 12 and Month 18
measure: Vineland Adaptive Behavior Scales-3 [Exploratory]
timeFrame: Month 6, Month 12 and Month 18
Locations:
city: Aurora
country: United States
facility: Children's Hospital Colorado
state: Colorado
city: Atlanta
country: United States
facility: Rare Disease Research Center
state: Georgia
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
Study officials:
affiliation: Harvard University
name: Susan E Waisbren, PhD
role: STUDY_CHAIR
affiliation: University of Rochester
name: Jonathan W Mink, MD
role: STUDY_CHAIR
References: