Clinical trial NCT05064878: A Study to Investigate the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: CDKL5 Deficiency Disorder
Generalized Tonic Clonic Seizure
Epileptic Spasm
Refractory Seizures
Lead sponsor: UCB Pharma
Sponsor class: INDUSTRY
First posted: 2021-10-01
Enrollment: 87
Sex: ALL
Minimum age (years): 1
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: The median percentage change from the Baseline Period (Baseline) in "monthly (28 days) countable motor seizure frequency
timeFrame: 14 Weeks
Secondary outcomes:
measure: The percentage of subjects who achieve a ≥ 50% reduction from Baseline in CMSF
timeFrame: 14 Weeks
measure: The percentage of subjects who achieve improvement in the Clinical Global Impression-Improvement (CGI-I) rating as assessed by the Investigator
timeFrame: 14 Weeks
measure: The median percentage change from Baseline in monthly Generalized Tonic-Clonic (GTC) seizure frequency
timeFrame: 14 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Ep0216 154
state: Alabama
city: Los Angeles
country: United States
facility: Ep0216 144
state: California
city: San Francisco
country: United States
facility: Ep0216 101
state: California
city: Aurora
country: United States
facility: Ep0216 173
state: Colorado
city: Washington
country: United States
facility: Ep0216 149
state: District of Columbia
city: Atlanta
country: United States
facility: Ep0216 157
state: Georgia
city: Boston
country: United States
facility: Ep0216 113
state: Massachusetts
city: Detroit
country: United States
facility: Ep0216 134
state: Michigan
city: Chapel Hill
country: United States
facility: Ep0216 166
state: North Carolina
city: Cleveland
country: United States
facility: Ep0216 164
state: Ohio
city: Philadelphia
country: United States
facility: Ep0216 120
state: Pennsylvania
city: Memphis
country: United States
facility: Ep0216 124
state: Tennessee
city: Austin
country: United States
facility: Ep0216 171
state: Texas
city: Linz
country: Austria
facility: Ep0216 2505
city: Brussels
country: Belgium
facility: Ep0216 804
city: Edegem
country: Belgium
facility: Ep0216 801
city: Tbilisi
country: Georgia
facility: Ep0216 2802
city: Bielefeld
country: Germany
facility: Ep0216 902
city: Kehl-Kork
country: Germany
facility: Ep0216 909
city: Kiel
country: Germany
facility: Ep0216 908
city: Vogtareuth
country: Germany
facility: Ep0216 901
city: Dublin
country: Ireland
facility: Ep0216 1803
city: Petah tikva
country: Israel
facility: Ep0216 1909
city: Ramat Gan
country: Israel
facility: Ep0216 1906
city: Tel Aviv
country: Israel
facility: Ep0216 1904
city: Florence
country: Italy
facility: Ep0216 1201
city: Genova
country: Italy
facility: Ep0216 1204
city: Modena
country: Italy
facility: Ep0216 1212
city: Roma
country: Italy
facility: Ep0216 1206
city: Roma
country: Italy
facility: Ep0216 1208
city: Verona
country: Italy
facility: Ep0216 1202
city: Hiroshima
country: Japan
facility: Ep0216 1512
city: Niigata
country: Japan
facility: Ep0216 1505
city: Shizuoka
country: Japan
facility: Ep0216 1502
city: Ōmura
country: Japan
facility: Ep0216 1518
city: Zwolle
country: Netherlands
facility: Ep0216 1401
city: Lisboa
country: Portugal
facility: Ep0216 2104
city: Porto
country: Portugal
facility: Ep0216 2105
city: Barcelona
country: Spain
facility: Ep0216 1103
city: Madrid
country: Spain
facility: Ep0216 1117
city: Santiago De Compostela
country: Spain
facility: Ep0216 1118
city: Dubai
country: United Arab Emirates
facility: Ep0216 3101
city: Bristol
country: United Kingdom
facility: Ep0216 607
city: London
country: United Kingdom
facility: Ep0216 602
city: Manchester
country: United Kingdom
facility: Ep0216 611
city: Sheffield
country: United Kingdom
facility: Ep0216 604
Study officials:
affiliation: 001 844 599 2273
name: UCB Cares
role: STUDY_DIRECTOR
References: