Journal Article

Exit interviews with caregivers of pediatric patients with classic galactosemia to explore meaningfulness of changes in the ACTION-galactosemia kids trial

Perfetti, Riccardo, Randall, Jason A., Wang, Stella, Burbridge, Claire, Shendelman, Shoshana, Sutter, Carolyn, Bailey, Evan, Raither, Lydia

2025

Overview

Background Classic Galactosemia is a rare, autosomal recessive disease in which galactose is not metabolized properly due to severe deficiency/absence of the galactose-1-phosphate uridylyltransferase (GALT) enzyme, converting to an aberrant and toxic metabolite, galactitol. Living with the debilitating symptoms and long-term consequences of Classic Galactosemia creates a heavy burden on patients’ and their families’ lives. Objectives were to: (1) Evaluate the impact and burden of disease; (2) Qualitatively explore changes in patient symptoms following treatment; and (3) Document the meaningfulness of changes resulting from treatment with govorestat as assessed by the Caregiver Global Impression of Severity (CGIS) and Caregiver Global Impression of Change (CGIC) scales. Methodology The AT-007-1002 clinical trial involved a Phase 1/2 dose escalation component (Part A) followed by a Phase 3, randomized, double-blind, placebo-controlled long-term administration component (Part B) that evaluated potential clinical benefit. Exit Interviews were completed prior to unblinding of data. The in-depth, qualitative interviews were semi-structured, using a discussion guide, and conducted by either Zoom or GoToMeeting. Thirty-six caregiver interviews were conducted, capturing the experience of 37 pediatric patients (one caregiver had 2 patients enrolled in the study). Thematic analysis was undertaken to identify themes or patterns within the data. All analyses were conducted on blinded data. Following finalization of the analysis and report findings, post-hoc analysis of the unblinded data was then conducted to explore the meaningfulness of patients experience by treatment arm. Results This study confirms the substantial burden known to be associated with Classic Galactosemia in a pediatric population. The difficulties experienced were across multiple areas including cognitive function, behavior/social function, motor function, emotional function, communication, vision problems, ovarian insufficiency, sensory difficulties, and sleep problems. The interviews demonstrated that most patients (approximately two thirds) experienced an improvement in symptoms and impacts associated with classic galactosemia over the course of the trial. Nearly all caregivers reported that they perceived a 1-category change on the Caregiver Global Impression of Severity or Caregiver Global Impression of Change items, indicating severity and change respectively, was meaningful to them and the patient. Unblinded analysis of the exit interview data confirmed the patient experience reported by caregivers was different between the treatment arms, providing qualitative support for the treatment benefit of govorestat when compared to placebo. Furthermore, the qualitative data from caregivers provide in-depth insights of their unique lived experience that highlight the substantial impact that this improvement had on the caregiver’s and the patient’s quality of life. The improvements observed led to a reduction on the burden of Classic Galactosemia and may lead to a greater patient’s greater independence. Conclusions The exit interviews confirmed the burden of Classic Galactosemia disease across multiple domains. Qualitative investigation suggests that observed changes are meaningful to the patient and caregiver, and changes were more commonly reported in those receiving govorestat compared to placebo. Full clinical trial findings will be published separately.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Activities of daily living / Adolescent / Age groups / Behavior / Beliefs, opinions and attitudes / Care and treatment / Caregiver / Caregivers / Child / Child, Preschool / Classic galactosemia / Clinical trials / Cognitive ability / Consent / Dietary restrictions / Double-Blind Method / Enzymes / Exit interview / Exit interviews (Human resource management) / Female / Galactose / Galactosemia / Galactosemias - drug therapy / Govorestat / Human Genetics / Humans / Male / Meaningful change / Medical treatment / Medicine / Medicine & Public Health / Mutation / Patients / Pediatric research / Pediatrics / Pharmacology/Toxicology / Physiological aspects / Placebos / Qualitative research / Quality of life / Sleep disorders / Social behavior / Testing