Effect of Ganaxolone on Quality of Life in Children with the CDKL5 Deficiency Disorder
Abstract number :
3.279
Submission category :
7. Anti-seizure Medications / 7B. Clinical Trials
Year :
2021
Submission ID :
1826312
Source :
www.aesnet.org
Presentation date :
12/6/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:53 AM
Authors :
Scott Demarest, MD - University of Colorado at Denver, Aurora, Colorado, USA.; Alex Aimetti, PhD – Marinus Pharmaceuticals; Eva Rybak, PharmD – Marinus Pharmaceuticals; Dayong Li, PhD – Marinus Pharmaceuticals; Joseph Hulihan, MD – Marinus Pharmaceuticals; Peter Jacoby – Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia; Helen Leonard, MBChB MPH – Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia; Jenny Downs, PhD – Telethon Kids Institute, The University of Western Australia, Perth, WA, Australia
Rationale: CDKL5 deficiency disorder (CDD) is a rare, X-linked, developmental epileptic encephalopathy. The Marigold study was the first phase 3 clinical trial conducted in CDD and evaluated the effect of ganaxolone, an investigational neuroactive steroid, on seizure control. It was previously reported that ganaxolone was associated with a significant reduction in the frequency of major motor seizures. This study explored whether ganaxolone was associated with improvement in quality of life (QOL) in children with CDD.
Methods: In this randomized, placebo-controlled trial, we recruited 2-19-year-old individuals with genetically confirmed CDD and 16 or more major motor seizures per month. Ganaxolone or placebo was administered 3 times a day over a 17-week double blind period. QOL was measured with the Quality of Life Inventory-Disability (QI-Disability) scale. QI-Disability comprises of six domains: Social Interaction (7 items), Positive Emotions (4 items), Negative Emotions (7 items), Physical Health (4 items), Leisure and the Outdoors (5 items), and Independence (5 items). Total and domain scores out of 100 were calculated where higher scores indicate better QOL. The effect of ganaxolone on QOL scores was compared using ANOVA adjusting for child age, sex, number of anti-seizure mediations, baseline 28-day frequency of major motor seizures, and baseline developmental skills and quality of life scores. ANOVA was also used to evaluate the effect of the percentage change in major motor seizure frequency on QOL scores, adjusting for child age, sex, number of anti-seizure mediations and baseline quality of life scores.
Results: 101 children with CDD from 39 clinical sites in 8 countries were randomized. Their median (IQR) age was 6 (3-10) years, 79.2% were female and 50 received ganaxolone. After 17 weeks of treatment, the total change in QOL score for children in the ganaxolone group was 4.04 points (95%CI -0.60,8.55, p=0.087) higher than in the placebo group. Changes in the Social Interaction domains scores were higher in ganaxolone-treated patients for (mean diff 7.4, 95%CI -0.45, 15.3, p=0.064) although confidence intervals were wide. Changes in QOL were similar between the two treatment groups for the Physical Health, Positive Emotions, Negative Emotions, Leisure and the Outdoors, and Independence domain scores. Changes in total and domain QOL scores were independent of the co-occurring percentage change in major motor seizure frequency (total QOL score, p=0.774).
Conclusions: QOL is a critical outcome for evaluating the success of interventions. Along with a reduction in frequency of major motor seizures, children who received ganaxolone had higher QOL scores than children in the placebo group when controlling for potential confounding factors although the estimates lacked precision. Future analysis of the Marigold data will investigate the reasons for improved QOL following administration of ganaxolone.
Funding: Please list any funding that was received in support of this abstract.: This study was supported by Marinus Pharmaceuticals.
Anti-seizure Medications