Abstracts

Rationale: Recent preclinical experiments using enzyme replacement or gene therapies have shown promising results and could be the future of drug development in CDKL5 Deficiency Disorder (CDD), a rare developmental and epileptic encephalopathy. A pre-competitive collaboration has been created aiming at harmonizing the clinical endpoint selection (aside EEG and seizure endpoints) for potential efficacy trials in CDD. The purpose of the Clinical Assessment of NeuroDevelopmental measures In CDD (CANDID) study is to evaluate the feasibility and suitability of neurocognitive tests and functioning scales, in patients with CDD, with the aim of defining relevant endpoints for future clinical trials.


Methods: The study involves twenty-two clinical sites from seven countries and prospectively follows participants over 3 years. Here, we present baseline data from this observational CANDID study.

Results: CANDID enrolled one hundred and twelve patients divided through four age groups (0-2, 3-6, 7-13 and 14+ years). Most enrolled patients were female (92%), with a mean (range) age of 8.4 (0.5-28) years, with 11 adult participants. The median (range) age of seizure onset was 1.5 (0-72) months. Patients used a mean (SD) of 2.8 (1.23) anti-seizure therapies at baseline. Seventy-nine percent of the patient seizure diaries collected within the first months of the study documented more than 16 seizures per month. Analysis of the Gross Motor Function Measure (GMFM) scores indicated a clear floor effect for the crawling, standing and walking levels in all age groups. Vineland 3 (interview form) and Bayley 4 growth scores could be derived for almost all participants, with increasing Vineland 3 scores with age for the receptive language, fine and gross motor domains. Floor effects were observed in the written, domestic and community domains. The Bruni questionnaire was used to evaluate sleep impairments and baseline scores clearly identified excessive somnolence, sleep-awake transition and sleep initiation as the most disrupted components without any difference between the age groups. The mean (SD) Quality of Life Inventory-Disability (QI-Disability) total scores ranged from 54 (14.6) to 65 (18.7) without significant differences across the age groups, with the independence domain being the most impacted.

Conclusions: Baseline data from the CANDID study demonstrated the feasibility and suitability of the Vineland 3 interview form, or the Bayley 4 for the assessment of adaptive function and neurodevelopment in future clinical trials with CDD patients. The GMFM revealed some operational and scoring weaknesses as a potential CDD endpoint.

Funding: Amicus Therapeutics; Biogen; Elaaj Bio; Marinus Pharmaceuticals; PTC Therapeutics; UCB; Ultragenyx Pharmaceuticals