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

NCT ID: NCT05064878

Last Updated: 2025-11-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE3

Total Enrollment

87 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-03-08

Study Completion Date

2027-11-08

Brief Summary

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This is a multicenter, double-blind, parallel-group, placebo controlled, 2-part study to evaluate the efficacy and safety of ZX008 when used as adjunctive therapy for the treatment of uncontrolled seizures in children and adults with cyclin-dependent kinase like-5 (CDKL5) deficiency disorder (CDD).

Detailed Description

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This is a 2-part multicenter trial. Part 1 is a 20-week randomized, double-blind, placebo-controlled, fixed-dose, parallel-group study to examine the efficacy and safety of ZX008 as an adjunctive therapy (to existing concomitant treatment with antiepileptic treatments \[AETs\]) in children and adults with a CDD diagnosis and uncontrolled seizures.

Part 1 of the study is 20 weeks in duration and will consist of the following stages: Baseline Period (ie, Baseline \[BL\]; 4 weeks including the Screening Visit and baseline observation), Titration Period (ie, Titration; 2 weeks), Maintenance Period (ie, Maintenance; 12 weeks), and a 2-week Transition Period (ie, Transition; 2 weeks) to the open-label starting dose.

Part 2 is a 54-week, open-label, flexible-dose, long-term extension for subjects who complete Part 1. Part 2 includes an Open-Label Extension (OLE) Treatment Period (52 weeks) with a Taper Period (ie, Taper; 2 weeks).

The primary study analysis to evaluate the efficacy and safety of ZX008 in children and adults with CDD will be based on Part 1 data in all randomized subjects.

Conditions

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CDKL5 Deficiency Disorder Generalized Tonic Clonic Seizure Epileptic Spasm Refractory Seizures

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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ZX008 0.8 mg/kg/day

Part 1: 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.

Group Type EXPERIMENTAL

ZX008 (Fenfluramine Hydrochloride)

Intervention Type DRUG

ZX008 is supplied as an oral aqueous solution of Fenfluramine Hydrochloride.

Placebo

Part 1: Matching ZX008 placebo will be administered twice a day (BID) in equally divided doses with or without food.

Group Type PLACEBO_COMPARATOR

Matching ZX008 Placebo

Intervention Type DRUG

Matching ZX008 placebo is supplied as an oral solution.

ZX008

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.

Group Type EXPERIMENTAL

ZX008 (Fenfluramine Hydrochloride)

Intervention Type DRUG

ZX008 is supplied as an oral aqueous solution of Fenfluramine Hydrochloride.

Interventions

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ZX008 (Fenfluramine Hydrochloride)

ZX008 is supplied as an oral aqueous solution of Fenfluramine Hydrochloride.

Intervention Type DRUG

Matching ZX008 Placebo

Matching ZX008 placebo is supplied as an oral solution.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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 has participated in another interventional clinical trial within 30 days of the Screening Visit or is currently receiving an investigational product.
* Subject has previously been treated with Fintepla® (fenfluramine) prior to the Screening Visit.
Minimum Eligible Age

1 Year

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Zogenix, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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UCB Cares

Role: STUDY_DIRECTOR

001 844 599 2273

Locations

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Ep0216 154

Birmingham, Alabama, United States

Site Status

Ep0216 144

Los Angeles, California, United States

Site Status

Ep0216 101

San Francisco, California, United States

Site Status

Ep0216 173

Aurora, Colorado, United States

Site Status

Ep0216 149

Washington D.C., District of Columbia, United States

Site Status

Ep0216 157

Atlanta, Georgia, United States

Site Status

Ep0216 113

Boston, Massachusetts, United States

Site Status

Ep0216 134

Detroit, Michigan, United States

Site Status

Ep0216 166

Chapel Hill, North Carolina, United States

Site Status

Ep0216 164

Cleveland, Ohio, United States

Site Status

Ep0216 120

Philadelphia, Pennsylvania, United States

Site Status

Ep0216 124

Memphis, Tennessee, United States

Site Status

Ep0216 171

Austin, Texas, United States

Site Status

Ep0216 2505

Linz, , Austria

Site Status

Ep0216 804

Brussels, , Belgium

Site Status

Ep0216 801

Edegem, , Belgium

Site Status

Ep0216 2802

Tbilisi, , Georgia

Site Status

Ep0216 902

Bielefeld, , Germany

Site Status

Ep0216 909

Kehl-Kork, , Germany

Site Status

Ep0216 908

Kiel, , Germany

Site Status

Ep0216 901

Vogtareuth, , Germany

Site Status

Ep0216 1803

Dublin, , Ireland

Site Status

Ep0216 1909

Petah Tikva, , Israel

Site Status

Ep0216 1906

Ramat Gan, , Israel

Site Status

Ep0216 1904

Tel Aviv, , Israel

Site Status

Ep0216 1201

Florence, , Italy

Site Status

Ep0216 1204

Genova, , Italy

Site Status

Ep0216 1212

Modena, , Italy

Site Status

Ep0216 1206

Roma, , Italy

Site Status

Ep0216 1208

Roma, , Italy

Site Status

Ep0216 1202

Verona, , Italy

Site Status

Ep0216 1512

Hiroshima, , Japan

Site Status

Ep0216 1505

Niigata, , Japan

Site Status

Ep0216 1518

Ōmura, , Japan

Site Status

Ep0216 1502

Shizuoka, , Japan

Site Status

Ep0216 1401

Zwolle, , Netherlands

Site Status

Ep0216 2104

Lisbon, , Portugal

Site Status

Ep0216 2105

Porto, , Portugal

Site Status

Ep0216 1103

Barcelona, , Spain

Site Status

Ep0216 1117

Madrid, , Spain

Site Status

Ep0216 1118

Santiago de Compostela, , Spain

Site Status

Ep0216 3101

Dubai, , United Arab Emirates

Site Status

Ep0216 607

Bristol, , United Kingdom

Site Status

Ep0216 602

London, , United Kingdom

Site Status

Ep0216 611

Manchester, , United Kingdom

Site Status

Ep0216 604

Sheffield, , United Kingdom

Site Status

Countries

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United States Austria Belgium Georgia Germany Ireland Israel Italy Japan Netherlands Portugal Spain United Arab Emirates United Kingdom

Other Identifiers

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2021-003222-76

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1303-2043

Identifier Type: OTHER

Identifier Source: secondary_id

ZX008-2103/EP0216

Identifier Type: -

Identifier Source: org_study_id