Efficacy and Safety Evaluation of Hyperthermic Baths in the Treatment of Seizures in Children With CDKL5 Deficiency

Inclusion Criteria:

• A diagnosis of CDKL5 deficiency, including molecular confirmation of a pathogenic orlikely pathogenic CDKL5 variant and refractory seizures

• Male or female participants aged 6 months to less than 6 years

• Parent(s) or LAR willing to give written informed consent, after being properlyinformed of the nature and risks of the study and prior to engaging in anystudy-related procedures

• Failure to control seizures despite appropriate trial of 1 or more anti-seizuremedications at therapeutic doses

• Have a history of at least 16 countable seizures per 4 weeks during the 8 weeksprior to screening. Countable seizures will be defined by the following:Seizureswith or without impairment of consciousness with a clear motor component, includinggeneralized tonic-clonic, focal to bilateral tonic-clonic, atonic, bilateral clonic,bilateral tonic, focal motor seizures with or without impaired awareness, orinfantile spasms. Clusters of infantile spasms/tonic seizures will be counted as asingle seizure.

• Participants should be on a stable regimen of anti-seizure medications for ≥ 4 weeksprior to the screening visit, without a foreseeable change in dosing for theduration of the DB phase.

• Vagus nerve stimulator (VNS) are permitted, but should be implanted for 1 year priorto screening and settings should be unchanged throughout the study.

• Parent/caregiver is able and willing to maintain an accurate and complete dailyseizure eDiary for the duration of the study.

Exclusion Criteria:

• Any history of previous brain disease (trauma, etc.) that likely to precipitateseizures.

• Tissue damage (eczema, etc.) in the area where hyperthermic baths will be applied onthe skin.

• Seizures associated with hyperthermic baths.

• Presence of any clinical condition that in the opinion of the principal investigatormakes the patient not suitable to participate in the trial.