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

CDKL5 Deficiency Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05064878
• Other study ID #: ZX008-2103/EP0216
• Secondary ID: 2021-003222-76U1
• Status: Recruiting
• Phase: Phase 3
• Start date: March 8, 2022
• Est. completion date: June 16, 2026

Study information

• Verified date: May 2024
• Source: UCB Pharma
• Contact: UCB Cares
• Phone: 1-844-599-2273 (USA)
• Email: ucbcares[@]ucb.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: June 16, 2026
• Est. primary completion date: February 5, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Year to 35 Years

Eligibility

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.

Related Conditions & MeSH terms

• CDKL5 Deficiency Disorder
• Generalized Tonic Clonic Seizure
• Seizures

Intervention

Drug:
• ZX008 (Fenfluramine Hydrochloride)
ZX008 is supplied as an oral aqueous solution of Fenfluramine Hydrochloride.
• Matching ZX008 Placebo
Matching ZX008 placebo is supplied as an oral solution.

Locations

Country	Name	City	State
Austria	Ep0216 2505	Linz
Belgium	Ep0216 804	Brussels
Belgium	Ep0216 801	Edegem
Georgia	Ep0216 2802	Tbilisi
Germany	Ep0216 902	Bielefeld
Germany	Ep0216 909	Kehl-Kork
Germany	Ep0216 908	Kiel
Ireland	Ep0216 1801	Cork
Ireland	Ep0216 1803	Dublin
Israel	Ep0216 1906	Ramat Gan
Israel	Ep0216 1904	Tel Aviv
Japan	Ep0216 1512	Hiroshima
Japan	Ep0216 1505	Niigata
Japan	Ep0216 1518	Omura
Japan	Ep0216 1502	Shizuoka
Netherlands	Ep0216 1401	Zwolle
Portugal	Ep0216 2104	Lisboa
Portugal	Ep0216 2105	Porto
Spain	Ep0216 1103	Barcelona
Spain	Ep0216 1114	Madrid
Spain	Ep0216 1116	Madrid
Spain	Ep0216 1117	Madrid
Spain	Ep0216 1118	Santiago De Compostela
Spain	Ep0216 1115	Valencia
United Kingdom	Ep0216 607	Bristol
United Kingdom	Ep0216 602	London
United Kingdom	Ep0216 604	Sheffield
United States	Ep0216 151	Atlanta	Georgia
United States	Ep0216 157	Atlanta	Georgia
United States	Ep0216 173	Aurora	Colorado
United States	Ep0216 171	Austin	Texas
United States	Ep0216 154	Birmingham	Alabama
United States	Ep0216 113	Boston	Massachusetts
United States	Ep0216 166	Chapel Hill	North Carolina
United States	Ep0216 160	Charleston	South Carolina
United States	Ep0216 133	Cincinnati	Ohio
United States	Ep0216 164	Cleveland	Ohio
United States	Ep0216 146	Dallas	Texas
United States	Ep0216 134	Detroit	Michigan
United States	Ep0216 126	Fort Worth	Texas
United States	Ep0216 136	Grand Rapids	Michigan
United States	Ep0216 122	Los Angeles	California
United States	Ep0216 144	Los Angeles	California
United States	Ep0216 124	Memphis	Tennessee
United States	Ep0216 153	Nashville	Tennessee
United States	Ep0216 118	New York	New York
United States	Ep0216 130	Orange	California
United States	Ep0216 165	Orlando	Florida
United States	Ep0216 120	Philadelphia	Pennsylvania
United States	Ep0216 109	Rochester	Minnesota
United States	Ep0216 101	San Francisco	California
United States	Ep0216 125	Tacoma	Washington
United States	Ep0216 149	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Zogenix, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Georgia,  Germany,  Ireland,  Israel,  Japan,  Netherlands,  Portugal,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The median percentage change from the Baseline Period (Baseline) in "monthly (28 days) countable motor seizure frequency	The median percentage change from the Baseline Period (Baseline) in "monthly (28 days) countable motor seizure frequency," or CMSF, during the combined Titration and Maintenance Periods (T+M) in the ZX008 0.8 mg/kg/day group compared with the placebo group	14 Weeks
Secondary	The percentage of subjects who achieve a = 50% reduction from Baseline in CMSF	The percentage of subjects who achieve a = 50% reduction from Baseline in CMSF during T+M in the ZX008 0.8 mg/kg/day group compared with the placebo group	14 Weeks
Secondary	The percentage of subjects who achieve improvement in the Clinical Global Impression-Improvement (CGI-I) rating as assessed by the Investigator	The percentage of subjects who achieve a CGI-I rating of much or very much improved as assessed by the Investigator at the end of T+M in the ZX008 0.8 mg/kg group compared with the placebo group	14 Weeks
Secondary	The median percentage change from Baseline in monthly Generalized Tonic-Clonic (GTC) seizure frequency	The median percentage change from Baseline in monthly GTC seizure frequency during T+M in the ZX008 0.8 mg/kg/day group compared with the placebo group	14 Weeks