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A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose, Multicenter Study To Examine The Efficacy And Safety Of ZX008 In Subjects With CDKL5 Deficiency Disorder Followed By An Open-Label Extension

A Study to Investigate the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder

Soma Tadaharu

UCB Japan Co., Ltd.

8-17-1 Nishi-shinjuku, Shinjuku-ku, Tokyo

CTR-JRCT.UCBJapan@ucb.com

Global Clinical Science & Operation

UCB Japan Co., Ltd.

8-17-1 Nishi-shinjuku, Shinjuku-ku, Tokyo

+81-3-6864-7500

CTR_SCC_UCBJapan@UCB.com

Recruiting

April. 28, 2023

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- Subject has a confirmed pathogenic or likely pathogenic mutation in the CDKL5 gene and a clinical diagnosis of CDD with epilepsy onset in the first year of life, plus motor and developmental delays.
- Subject is male or female, aged 1 to 35 years, inclusive, as of the day of the Screening Visit.
- Subject must have failed to achieve seizure control despite previous or current use of 2 or more AETs.
- Subject is currently receiving at least 1 concomitant antiseizure treatment: antiseizure medication (ASM), vagus nerve stimulation (VNS), responsive neurostimulation (RNS), or ketogenic diet (KD).
- All medications or interventions for epilepsy (including VNS, RNS, and KD) must be stable prior to screening and are expected to remain stable throughout the study.
- At the Screening Visit, parent/caregiver reports that subject has >= 4 countable motor seizures(CMS) per week.

- Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study drug.
- Subject has a diagnosis of pulmonary arterial hypertension.
- Subject has a clinically significant medical condition, including chronic obstructive pulmonary disease, interstitial lung disease, or portal hypertension, or has had clinically relevant symptoms or a clinically significant illness currently or in the 4 weeks prior to the Screening Visit, other than epilepsy, that would negatively impact study participation, collection of study data, or pose a risk to the subject.
- Subject has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke, severe ventricular arrhythmias, or clinically significant structural cardiac abnormality, including but not limited to mitral valve prolapse, atrial or ventricular septal defects, patent ductus arteriosus, and patent foramen ovale with reversal of shunt. (Note: Patent foramen ovale or a bicuspid aortic valve are not considered exclusionary).
- Subject has moderate to severe hepatic impairment.
- Subject has current eating disorder that suggests anorexia nervosa or bulimia.
- Subject has a current or past history of glaucoma.
- Subject is taking > 4 concomitant ASMs. Rescue medications are not included in the count.
- Subject is receiving concomitant treatment with cannabidiol (CBD) other than Epidiolex/Epidyolex or is being actively treated with tetrahydrocannabinol (THC) or any marijuana product for any condition.
- Subject is currently receiving another investigational product(s) or has received another investigational product within 30 days or within < 5 times the half-lives of the investigational product, whichever is longer, prior to the Screening Visit.
- Subject has previously been treated with Fintepla (fenfluramine) prior to the Screening Visit.

Both

CDKL5 Deficiency Disorder

Part 1:
- Experimental (ZX008): ZX008 0.8 mg/kg/day will be administered twice a day (BID) in equally divided doses; maximum of 30 mg/day, (subjects taking concomitant stiripentol will receive 0.5 mg/kg/day, [maximum of 20 mg/day]) with or without food.
- Placebo: Matching ZX008 placebo will be administered twice a day (BID) in equally divided doses with or without food.

Part 2:
Open-label ZX008 will be administered using a flexible dosing regimen, up to ZX008 0.8 mg/kg/day; maximum dose: 30 mg/day (subjects taking concomitant stiripentol will receive 0.5 mg/kg/day, [maximum of 20 mg/day]). ZX008 will be administered twice a day (BID) in equally divided doses with or without food.

The median percentage change from the Baseline Period (Baseline) in monthly (28 days) countable motor seizure frequency

+81-54-245-5446

Feb. 17, 2023

Yes

Plan Description: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe, or global development is discontinued, and 18 months after trial completion. Investigators may request access to anonymized individual patient-level data and redacted trial documents which may include: analysis-ready datasets, study protocol, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a prespecified time, typically 12 months, on a password protected portal. This plan may change if the risk of re-identifying trial participants is determined to be too high after the trial is completed; in this case and to protect participants, individual patient-level data would not be made available. IPD Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion. IPD Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed. All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal. IPD URL https://www.vivli.org

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