Clinical Benefit, Safety, PK and PD Study of AT-007 in Pediatric Subjects With Classic Galactosemia

Applied Therapeutics, Inc.47 enrolled

Overview

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).

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Classic Galactosemia

Interventions

AT-007DRUG

Treatment with AT-007 given orally

PlaceboOTHER

Placebo given orally

Eligibility

Sex: ALLMin age: 2 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (3)

Children's Hospital Colorado

Aurora, Colorado, United States

Rare Disease Research Center

Atlanta, Georgia, United States

University of Michigan

Ann Arbor, Michigan, United States

Outcomes

Primary Outcomes

Global Statistical Test (GST)

The primary endpoint is a GST of four components: 1) Behavioral Symptoms Index of the Behavioral Assessment Scale for Children 3 (BASC-3); 2) Activities of Daily Living from the BASC-3; 3) Oral Expression from the Oral and Written Language Skills-II (OWLS-II); 4) Listening Comprehension from the OWLS-II. Each individual component is also a secondary endpoint on their own with the test and scoring described below in the secondary endpoint section. For the GST, change from baseline using standardized z-scores is calculated for active versus placebo.

Time frame: Month 6, Month 12 and Month 18

Sensitivity Analysis of the Primary Endpoint (GST) with Cognition

Sensitivity Analysis adding the National Institutes of Health Toolbox Cognition Battery (NIH-CB) test which measures cognition. NIH-CB is described below in the secondary endpoints. For the GST with cognition, change from baseline using standardized z-scores is calculated for active versus placebo.

Time frame: Month 6, Month 12 and Month 18

Sensitivity Analysis of the Primary Endpoint (GST) with Fine Motor Skills

Sensitivity Analysis adding the National Institutes of Health Toolbox Motor Battery (NIH-MB) 9-Hole Pegboard test which measures fine motor skills. NIH-MB is described below in the secondary endpoints. For the GST with fine motor skills, change from baseline using standardized z-scores is calculated for active versus placebo.

Time frame: Month 6, Month 12 and Month 18

Secondary Outcomes

Galactitol Level

The change from baseline in plasma galactitol (Pharmacodynamic measure)

Time frame: Month 1, Month 2, Month 3, Month 6, Month 12, and Month 18

Behavioral Assessment System for Children-3 [Individual Components]

Behavioral Assessment System for Children (BASC-3) has a normal range of 40-60 with the higher score showing more difficulty. There are multiple outcome scores included such as: Behavioral Symptoms Index, Activities of Daily Living, Withdrawal, Adapatability, Adaptive Skills, Socialization, and Functional Impairment Index.

Data from ClinicalTrials.gov

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