Exploring concurrent validity of the CLN2 Clinical Rating Scale

TY - JOUR

T1 - Exploring concurrent validity of the CLN2 Clinical Rating Scale

T2 - Comparison to PedsQL using cerliponase alfa clinical trial data

AU - Specchio, Nicola

AU - Gissen, Paul

AU - de Los Reyes, Emily

AU - Olaye, Andrew

AU - Camp, Charlotte

AU - Curteis, Tristan

AU - Griffiths, Annabel

AU - Butt, Thomas

AU - Cohen-Pfeffer, Jessica

AU - Slasor, Peter

AU - Sisic, Zlatko

AU - Jain, Mohit

AU - Schulz, Angela

N1 - Copyright: © 2024 Specchio et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2024/5/22

Y1 - 2024/5/22

N2 - BACKGROUND: The CLN2 Clinical Rating Scale evaluates disease progression in CLN2 disease, an ultra-rare, neurodegenerative disorder with late infantile onset. To validate the Clinical Rating Scale, a comparison with the Pediatric Quality of Life Inventory (PedsQL) was conducted utilising clinical trial data investigating cerliponase alfa use in CLN2 disease.METHODS: Linear regression and mixed effects models were used to investigate the relationship between the Clinical Rating Scale and PedsQL using open-label, single-arm, phase 1/2 (NCT01907087) and ongoing extension study (NCT02485899) data of 23 children with CLN2 disease treated with cerliponase alfa for ≥96 weeks.RESULTS: Correlations between the four Clinical Rating Scale domains were low. Linear mixed effects analyses showed significant correlation between PedsQL and Clinical Rating Scale (Total score or motor-language [ML] score adjusted p-values <0.05), driven by the relationship with the PedsQL Physical domain. A statistically significant relationship was identified between the Clinical Rating Scale motor domain and PedsQL (Total score: adjusted p-value = 0.048, parameter estimate [PE] = 8.10; Physical domain score: adjusted p-value = 0.012; PE = 13.79).CONCLUSIONS: Each domain of the Clinical Rating Scale provides unique information on disease state. Validity of the scale is supported by its relationship with the PedsQL. Among the four domains of the Clinical Rating Scale, motor has the highest correlation to PedsQL, suggesting motor function as a driver of patients' quality of life. The lack of association between the remaining domains of the Clinical Rating Scale and PedsQL suggests that additional disease-specific measures may be needed to fully capture the quality of life impact of CLN2 disease.TRIAL REGISTRATION: NCT01907087, NCT02485899.

AB - BACKGROUND: The CLN2 Clinical Rating Scale evaluates disease progression in CLN2 disease, an ultra-rare, neurodegenerative disorder with late infantile onset. To validate the Clinical Rating Scale, a comparison with the Pediatric Quality of Life Inventory (PedsQL) was conducted utilising clinical trial data investigating cerliponase alfa use in CLN2 disease.METHODS: Linear regression and mixed effects models were used to investigate the relationship between the Clinical Rating Scale and PedsQL using open-label, single-arm, phase 1/2 (NCT01907087) and ongoing extension study (NCT02485899) data of 23 children with CLN2 disease treated with cerliponase alfa for ≥96 weeks.RESULTS: Correlations between the four Clinical Rating Scale domains were low. Linear mixed effects analyses showed significant correlation between PedsQL and Clinical Rating Scale (Total score or motor-language [ML] score adjusted p-values <0.05), driven by the relationship with the PedsQL Physical domain. A statistically significant relationship was identified between the Clinical Rating Scale motor domain and PedsQL (Total score: adjusted p-value = 0.048, parameter estimate [PE] = 8.10; Physical domain score: adjusted p-value = 0.012; PE = 13.79).CONCLUSIONS: Each domain of the Clinical Rating Scale provides unique information on disease state. Validity of the scale is supported by its relationship with the PedsQL. Among the four domains of the Clinical Rating Scale, motor has the highest correlation to PedsQL, suggesting motor function as a driver of patients' quality of life. The lack of association between the remaining domains of the Clinical Rating Scale and PedsQL suggests that additional disease-specific measures may be needed to fully capture the quality of life impact of CLN2 disease.TRIAL REGISTRATION: NCT01907087, NCT02485899.

KW - Humans

KW - Quality of Life

KW - Female

KW - Male

KW - Neuronal Ceroid-Lipofuscinoses/drug therapy

KW - Child

KW - Tripeptidyl-Peptidase 1

KW - Child, Preschool

KW - Adolescent

KW - Dipeptidyl-Peptidases and Tripeptidyl-Peptidases

KW - Severity of Illness Index

KW - Disease Progression

KW - Recombinant Proteins

U2 - 10.1371/journal.pone.0302382

DO - 10.1371/journal.pone.0302382

M3 - SCORING: Journal article

C2 - 38776275

VL - 19

SP - e0302382

JO - PLOS ONE

JF - PLOS ONE

SN - 1932-6203

IS - 5

ER -