Back to resultsA Study to Investigate the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder
Primary Purpose
CDKL5 Deficiency Disorder, Generalized Tonic Clonic Seizure, Epileptic Spasm
Status
Recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ZX008 (Fenfluramine Hydrochloride)
Matching ZX008 Placebo
Sponsored by
About this trial
This is an interventional treatment trial for CDKL5 Deficiency Disorder
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.
Sites / Locations
- Ep0216 122
- Ep0216 144Recruiting
- Ep0216 130Recruiting
- Ep0216 101Recruiting
- Ep0216 165Recruiting
- Ep0216 151Recruiting
- Ep0216 113Recruiting
- Ep0216 134Recruiting
- Ep0216 136Recruiting
- Ep0216 109Recruiting
- Ep0216 118Recruiting
- Ep0216 166Recruiting
- Ep0216 133Recruiting
- Ep0216 164Recruiting
- Ep0216 124Recruiting
- Ep0216 153Recruiting
- Ep0216 171Recruiting
- Ep0216 126Recruiting
- Ep0216 125Recruiting
- Ep0216 804Recruiting
- Ep0216 902Recruiting
- Ep0216 909Recruiting
- Ep0216 1512Recruiting
- Ep0216 1505Recruiting
- Ep0216 1502Recruiting
- Ep0216 1518Recruiting
- Ep0216 1401Recruiting
- Ep0216 2104Recruiting
- Ep0216 2105Recruiting
- Ep0216 1117Recruiting
- Ep0216 604Recruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
ZX008 0.8 mg/kg/day
Placebo
ZX008
Arm Description
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.
Part 1: 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.
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
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
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
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05064878
Brief Title
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
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 8, 2022 (Actual)
Primary Completion Date
February 5, 2025 (Anticipated)
Study Completion Date
June 16, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Zogenix, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CDKL5 Deficiency Disorder, Generalized Tonic Clonic Seizure, Epileptic Spasm, Refractory Seizures
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
ZX008 0.8 mg/kg/day
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Part 1: Matching ZX008 placebo will be administered twice a day (BID) in equally divided doses with or without food.
Arm Title
ZX008
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
ZX008 (Fenfluramine Hydrochloride)
Intervention Description
ZX008 is supplied as an oral aqueous solution of Fenfluramine Hydrochloride.
Intervention Type
Drug
Intervention Name(s)
Matching ZX008 Placebo
Intervention Description
Matching ZX008 placebo is supplied as an oral solution.
Primary Outcome Measure Information:
Title
The median percentage change from the Baseline Period (Baseline) in "monthly (28 days) countable motor seizure frequency
Description
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
Time Frame
14 Weeks
Secondary Outcome Measure Information:
Title
The percentage of subjects who achieve a ≥ 50% reduction from Baseline in CMSF
Description
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
Time Frame
14 Weeks
Title
The percentage of subjects who achieve improvement in the Clinical Global Impression-Improvement (CGI-I) rating as assessed by the Investigator
Description
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
Time Frame
14 Weeks
Title
The median percentage change from Baseline in monthly Generalized Tonic-Clonic (GTC) seizure frequency
Description
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
Time Frame
14 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Year
Maximum Age & Unit of Time
35 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
UCB Cares
Phone
1-844-599-2273 (USA)
Email
ucbcares@ucb.com
First Name & Middle Initial & Last Name or Official Title & Degree
UCB Cares
Phone
001 844 599 2273
Email
ucbcares@ucb.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
UCB Cares
Organizational Affiliation
001 844 599 2273
Official's Role
Study Director
Facility Information:
Facility Name
Ep0216 122
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Withdrawn
Facility Name
Ep0216 144
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 130
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 101
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 165
City
Orlando
State/Province
Florida
ZIP/Postal Code
32806
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 151
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30329
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 113
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 134
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 136
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49503
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 109
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 118
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 166
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 133
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45229-3026
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 164
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 124
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 153
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 171
City
Austin
State/Province
Texas
ZIP/Postal Code
78731
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 126
City
Fort Worth
State/Province
Texas
ZIP/Postal Code
76104
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 125
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98405
Country
United States
Individual Site Status
Recruiting
Facility Name
Ep0216 804
City
Brussels
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Ep0216 902
City
Bielefeld
Country
Germany
Individual Site Status
Recruiting
Facility Name
Ep0216 909
City
Kehl-Kork
Country
Germany
Individual Site Status
Recruiting
Facility Name
Ep0216 1512
City
Hiroshima
Country
Japan
Individual Site Status
Recruiting
Facility Name
Ep0216 1505
City
Niigata
Country
Japan
Individual Site Status
Recruiting
Facility Name
Ep0216 1502
City
Shizuoka
Country
Japan
Individual Site Status
Recruiting
Facility Name
Ep0216 1518
City
Ōmura
Country
Japan
Individual Site Status
Recruiting
Facility Name
Ep0216 1401
City
Zwolle
Country
Netherlands
Individual Site Status
Recruiting
Facility Name
Ep0216 2104
City
Lisboa
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Ep0216 2105
City
Porto
Country
Portugal
Individual Site Status
Recruiting
Facility Name
Ep0216 1117
City
Madrid
Country
Spain
Individual Site Status
Recruiting
Facility Name
Ep0216 604
City
Sheffield
Country
United Kingdom
Individual Site Status
Recruiting
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing 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 pre-specified 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 Sharing 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 Sharing 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 Sharing URL
http://www.Vivli.org
Learn more about this trial
A Study to Investigate the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder
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