CDKL5 Deficiency DisorderPhase 3GEMZNCT05064878
A Phase 3 Study to Examine the Efficacy and Safety of ZX008 in Subjects With CDKL5 Deficiency Disorder.
A Phase 3 study testing Fenfluramine in people with CDKL5 Deficiency Disorder and Generalized Tonic Clonic Seizure, run by Zogenix, Inc. at 46 sites in 14 countries.
Trial summary
This is a Phase 3 Study to examine the efficacy and safety of ZX008 in children and adults with cyclin-dependent kinase like-5 (CDKL5) deficiency disorder (CDD). Read more about this study
- Who is it for?
- Ages 1 year to 35 years
- Conditions the study is for
- CDKL5 Deficiency Disorder, Generalized Tonic Clonic Seizure, Epileptic Spasm
- What is being tested?
- Fenfluramine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 87 participants
- Where
- 46 sitesin 14 countries
- Study dates
- 8 Mar 2022to 8 Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 year to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Subject has a confirmed pathogenic or likely pathogenic mutation in the CDKL5 gene and a clinical diagnosis of CDKL5 deficiency disorder (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 antiepileptic treatments (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.
Who cannot join
- 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 current eating disorder that suggests anorexia nervosa or bulimia.
- Subject has a current or past history of glaucoma.
Show all 11Show fewer
- Subject is taking > 4 concomitant antiseizure medications (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 moderate to severe hepatic impairment.
- 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.
Trial locations and contacts
46 sites in 14 countries.
46 sites in 14 countries
United States13 sites
Ep0216 157
Atlanta, Georgia, 30329
Ep0216 173
Aurora, Colorado, 80045
Ep0216 171
Austin, Texas, 78731
Ep0216 154
Birmingham, Alabama, 35233
Ep0216 113
Brookline, Massachusetts, 02115
Ep0216 166
Chapel Hill, North Carolina, 27514
Ep0216 164
Cleveland, Ohio, 44195
Ep0216 134
Detroit, Michigan, 48201
Ep0216 144
Los Angeles, California, 90095
Ep0216 124
Memphis, Tennessee, 38105
Ep0216 120
Philadelphia, Pennsylvania, 19104-4318
Ep0216 101
San Francisco, California, 94158
Ep0216 149
Washington D.C., District of Columbia, 20010
Italy6 sites
Ep0216 1201
Florence
Ep0216 1204
Genova
Ep0216 1212
Modena
Ep0216 1206
Roma
Ep0216 1208
Roma
Ep0216 1202
Verona
Germany4 sites
Ep0216 902
Bielefeld
Ep0216 909
Kehl-kork
Ep0216 908
Kiel
Ep0216 901
Vogtareuth
Japan4 sites
Ep0216 1512
Hiroshima
Ep0216 1505
Niigata
Ep0216 1518
Omura-shi
Ep0216 1502
Shizuoka
United Kingdom4 sites
Ep0216 607
Bristol
Ep0216 602
London
Ep0216 611
Manchester
Ep0216 604
Sheffield
Spain3 sites
Ep0216 1103
Barcelona
Ep0216 1117
Madrid
Ep0216 1118
Santiago de Compostela
About this study
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
This is a Phase 3 Study to examine the efficacy and safety of ZX008 in children and adults with cyclin-dependent kinase like-5 (CDKL5) deficiency disorder (CDD).
Read the detailed description
This is an up to 3-part multicenter study: a double-blind, placebo-controlled part (Part 1) which includes Baseline Period (4 weeks), Titration Period (2 weeks), Maintenance Period (12 weeks) and Transition Period (2 weeks), followed by up to 2 open-label extension (OLE) parts: Part 2 of 54 weeks [Treatment Period (52 weeks), Taper Period (2 weeks)] and Part 3, i.e., OLE1 and OLE2, respectively, with the addition of the second OLE part (Part 3/OLE2) only for participants who will continue on fenfluramine and have no alternative treatment access from another source (e.g., a managed access program [MAP]). Participants can remain in Part 3 until MAP access or approval of fenfluramine (ZX008) has been obtained from regulatory authorities for CDD in the participant's country of residence, or until the investigational product development for CDD is stopped by the Sponsor, whichever comes first. Participants who discontinue early from Part 1, Part 2, or Part 3 will attend a Cardiac Follow-Up Visit 6 months after their last dose of study drug.
- Conditions
- CDKL5 Deficiency Disorder, Generalized Tonic Clonic Seizure, Epileptic Spasm, Refractory Seizures
- Being tested
- Fenfluramine, Placebo
- Keywords
- CDD, CDKL5, fenfluramine
- Medical subject headings
- CDKL5 deficiency disorder, Epilepsy, Tonic-Clonic, Spasms, Infantile, Seizures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FenfluramineDrug
Also called FINTEPLA, ZX008, fenfluramine HCl, fenfluramine hydrochloride
Fenfluramine is supplied as an oral aqueous solution of fenfluramine hydrochloride.
PlaceboDrug
Matching fenfluramine (hydrochloride) placebo is supplied as an oral solution.
| Study group | Role | What they receive |
|---|---|---|
| Fenfluramine (hydrochloride) 0.8 mg/kg/day | Experimental | Part 1: Fenfluramine (hydrochloride) 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. Receives: Drug: Fenfluramine |
| Placebo | Placebo comparator | Part 1: Matching fenfluramine (hydrochloride) placebo will be administered twice a day (BID) in equally divided doses with or without food. Receives: Drug: Placebo |
| Fenfluramine (hydrochloride) Open-label | Experimental | Part 2 and Part 3: Open-label fenfluramine (hydrochloride) will be administered using a flexible dosing regimen, up to fenfluramine 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]). Fenfluramine (hydrochloride) will be administered twice a day (BID) in equally divided doses with or without food. Receives: Drug: Fenfluramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage Change from Baseline in Countable Motor Seizure Frequency (CMSF) (Part 1)
The median percentage change from the Baseline in monthly (per 28 days) CMSF during the combined Titration and Maintenance Periods with the fenfluramine (ZX008) 0.8 mg/kg/day group compared with the placebo group will be reported.
Measured: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 2)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Treatment Emergent Adverse Events (TEAEs) are defined as any AEs reported on or after the first dose of study medication.
Measured: Up to OLE1 Treatment Period Post-Dose Safety Follow-up Visit 17 (up to 70 weeks)
Percentage of Participants With Abnormal Physical Examination Findings (Part 2)
Abnormal findings of physical exam that is considered clinically significant by Principal Investigator (PI).
Measured: Up to End of Treatment (EoT)/Early Termination (ET) Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Percentage of Participants With Abnormal Neurological Examination Findings (Part 2)
Abnormal findings of neurological exam that is considered clinically significant by PI.
Measured: Up to EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Percentage of Participants with Positive Response to Self-harm Question (Part 2)
Measured: OLE1 Treatment Period Day 1 to OLE1 Treatment Period Post-Dose Safety Follow-up Visit 17 (up to 70 weeks)
Percentage of Participants with Increase in Valvular Regurgitation from Baseline (except absent to trace) (Part 2)
Valvular regurgitation will be assessed using a 2-dimensional (2-D) Color Doppler Echocardiography (ECHO).
Measured: Baseline (28 days), Cardiac Follow-up Visit 18 (up to 96 weeks)
Percentage of Participants with Pulmonary Arterial Hypertension (PASP > 35 mmHg) at any Time During Treatment on Repeat Testing (Part 2)
Measured: OLE1 Treatment Period Day 1 to EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Laboratory Parameters (Hematology) (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Laboratory Parameters (Hormones) (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Laboratory parameters (Chemistry) (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Laboratory Parameters (Urinalysis) (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Vital Signs (Blood pressure) (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Vital Signs (Heart rate) (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Vital Signs (Temperature) (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Vital Signs (Respiratory rate) (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Body Weight (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Tanner Staging (Part 2)
Measured: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Percentage of Participants with TEAEs (Part 3)
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Treatment Emergent Adverse Events are defined as any AEs reported on or after the first dose of study medication.
Measured: Up to OLE2 Period Post-Dose Safety Follow-up (up to 200 weeks)
Change from Baseline in Height (Part 3)
Measured: Baseline (28 days), OLE2 Period EoT/ET Visit 23 (up to 198 weeks)
Change from Baseline in Body Weight (Part 3)
Measured: Baseline (28 days), OLE2 Period EoT/ET Visit 23 (up to 198 weeks)
Percentage of Participants with Increase in Valvular Regurgitation from Baseline (except absent to trace) (Part 3)
Valvular regurgitation will be assessed using a 2 D Color Doppler ECHO.
Measured: Baseline (28 days), Cardiac Follow-up Visit (up to 295 weeks)
Percentage of Participants with Pulmonary Arterial Hypertension (PASP > 35 mmHg) at any Time During Treatment on Repeat Testing (Part 3)
Measured: OLE2 Period Day 1 to EoT/ET Visit 23 of OLE2 Period (up to 198 weeks)
Secondary outcomes (35)
Percentage of Participants Who Achieve a ≥ 50% Reduction from Baseline in CMSF (Part 1)
The percentage of participants who achieve a ≥ 50% reduction from Baseline in CMSF during T+M periods, in the fenfluramine 0.8 mg/kg/day group compared with the placebo group.
Measured: Baseline (28 days), Combined T+M Periods (14 weeks)
Percentage of Participants with a Clinical Global Impression-Improvement (CGI-I) Rating of 'Much Improved' or 'Very Much Improved' as Assessed by Investigator (Part 1)
The percentage of participants who achieve a CGI-I rating of much or very much improved as assessed by the Investigator at the end of T+M periods, in the fenfluramine 0.8 mg/kg group compared with the placebo group.
The CGI-I rating scale permits a global evaluation of the participant's improvement over time. The severity of a participant's condition is rated on a 7-point scale ranging from 1 (very much improved) to 7 (very much worse) as follows: 1=very much improved; 2=much improved; 3=minimally improved; 4=no change; 5=minimally worse; 6=much worse; 7=very much worse.
Measured: At the end of the combined T+M Periods (14 weeks)
Percentage Change From Baseline in Monthly Generalized Tonic-Clonic (GTC) Seizure Frequency (Part 1)
The median percentage change from Baseline in monthly GTC seizure frequency during T+M periods, in the fenfluramine 0.8 mg/kg/day group compared with the placebo group.
Measured: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
Categorized Percentage Change in Seizures from Baseline in CMSF (Part 1)
The categorized median percentage change in seizures from the Baseline in monthly (per 28 days) CMSF during the combined T+ M periods will be presented in the following categories: no reduction or worsening, ≥25%, ≥75%, or 100% reduction.
Measured: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
Percentage of Participants who Achieve "Near Seizure Freedom" (Part 1)
The percentage of participants who achieve near seizure freedom, defined as 0 or 1 seizures, during T+M, in the fenfluramine 0.8 mg/kg/day group compared with the placebo group.
Measured: Combined T+M Periods (14 weeks)
Percentage of Participants with a CGI-I Rating of 'Much Improved' or 'Very Much Improved' as Assessed by the Parent/Caregiver (Part 1)
The percentage of participants who achieve a CGI-I rating of much or very much improved as assessed by the by the parent/caregiver at the end of T+M periods, in the fenfluramine 0.8 mg/kg group compared with the placebo group.
Measured: At the end of the combined T+M Periods (14 weeks)
Percentage of Participants with Improvement (Minimal, Much or Very Much Improved) on the CGI-I Rating as Assessed, Independently, by the Investigator (Part 1)
The percentage of participants who achieve a CGI-I rating of minimal, much or very much improved as assessed, independently, by the Investigator at the end of T+M periods, in the fenfluramine 0.8 mg/kg group compared with the placebo group.
Measured: At the end of the combined T+M Periods (14 weeks)
Percentage of Participants with Improvement (Minimal, Much or Very Much Improved) on the CGI-I Rating as Assessed, Independently, by the Parent/Caregiver (Part 1)
The percentage of participants who achieve a CGI-I rating of minimal, much or very much improved as assessed, independently, by the parent/caregiver at the end of T+M periods, in the fenfluramine 0.8 mg/kg group compared with the placebo group.
Measured: At the end of the combined T+M Periods (14 weeks)
Percentage Change from Baseline in the Monthly Frequency of all Seizures (Part 1)
The percentage change from the Baseline in the monthly (per 28 days) frequency of all seizures during the combined T+M period.
Measured: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
Change from Baseline in the Monthly Frequency of Countable Motor Seizure (CMS)-free Days (Part 1)
The change from the Baseline in the monthly (per 28 days) frequency of CMS-free days during the combined T+M periods.
Measured: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
Percentage of Participants with TEAEs (Part 1)
An AE is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. A TEAEs was defined as any adverse events with a start date/time on or after dosing of the study medication and up to end of the maintenance period (14 weeks) inclusive after dosing of the study medication.
Measured: From Day of first dose to the End of the Maintenance Periods (up to 14 weeks)
Percentage of Participants With Abnormal Physical Examination Findings (Part 1)
Measured: Baseline, Visit 6 (Day 43), Visit 7 (Day 71), Visit 8 (Day 99)
Percentage of Participants With Abnormal Neurological Examination Findings (Part 1)
Measured: Baseline, Visit 6 (Day 43), Visit 8 (Day 99)
Percentage of Participants with Positive Response to Self-harm question (Part 1)
Measured: Baseline, Visit 5 (Day 15), Visit 6 (Day 43), Visit 7 (Day 71), Visit 8 (Day 99)
Percentage of Participants with Increase in Valvular Regurgitation from Baseline (except absent to trace) (Part 1)
Valvular regurgitation will be assessed using a 2-D Color Doppler ECHO.
Measured: From Day of first dose to the End of the Maintenance Period (up to 14 weeks)
Percentage of Participants with Pulmonary Arterial Hypertension (PASP > 35 mmHg) at any Time During Treatment on Repeat Testing (Part 1)
The safety and tolerability of fenfluramine (ZX008) will be assessed in pediatric and adult participants with CDD.
Measured: From Day of first dose to the End of the Maintenance Period (up to 14 weeks)
Change from Baseline in Laboratory parameters (Hematology) (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Laboratory parameters (Hormones) (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Laboratory parameters (Chemistry) (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Laboratory Parameters (Urinalysis) (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Vital signs (Blood pressure) (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Vital signs (Heart rate) (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Vital signs (Temperature) (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Vital signs (Respiratory rate) (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Body Weight (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Tanner Staging (Part 1)
Measured: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Percentage Change from Baseline in CMSF (Part 2)
The median percentage change from the Baseline in monthly (per 28 days) CMSF during the OLE Treatment Period.
Measured: Baseline (28 days), OLE1 Treatment Period (up to 52 weeks)
Categorized Percentage Change in Seizures from Baseline in CMSF (Part 2)
The categorized percentage change in seizures from the Baseline in monthly (per 28 days) CMSF during OLE Treatment Period will be presented in the following categories: no reduction or worsening, ≥25%, ≥50%, ≥75%, or 100% reduction.
Measured: Baseline (28 days), OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants who Achieve "Near Seizure Freedom" (Part 2)
The percentage of participants who achieve near seizure freedom, defined as 0 or 1 seizures, during the OLE Treatment Period.
Measured: OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants with a CGI-I Rating of 'Much or Very Much Improved' as Assessed by the Investigator (Part 2)
The percentage of participants who achieve a CGI-I rating of much or very much improved as assessed by the Investigator at the OLE Treatment Period.
Measured: At the End of the OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants with a CGI-I Rating of 'Much or Very Much Improved' as Assessed by the Parent/Caregiver (Part 2)
The percentage of participants who achieve a CGI-I rating of much or very much improved as assessed by the parent/caregiver at the OLE Treatment Period.
Measured: At the End of the OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants with Improvement (Minimal, Much or Very Much Improved) on the CGI-I Rating as Assessed, Independently, by the Investigator (Part 2)
The percentage of participants who achieve a CGI-I rating of minimal, much or very much improved as assessed by the Investigator at the OLE Treatment Period.
Measured: At the End of the OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants with Improvement (Minimal, Much or Very Much Improved) on the CGI-I Rating as Assessed by the Parent/Caregiver (Part 2)
The percentage of participants who achieve a CGI-I rating of minimal, much or very much improved as assessed by the parent/caregiver at the OLE Treatment Period.
Measured: At the End of the OLE1 Treatment Period (up to 52 weeks)
Percentage Change from Baseline in Monthly GTC Seizure Frequency (Part 2)
The median percentage change from baseline in monthly GTC seizure frequency during OLE Treatment Period.
Measured: Baseline (28 days), OLE1 Treatment Period (up to 52 weeks)
Change from Baseline in the Monthly Frequency of CMS-free Days (Part 2)
The change from the Baseline in the monthly (per 28 days) frequency of CMS-free days during the OLE Treatment Period.
Measured: Baseline (28 days), OLE1 Treatment Period (up to 52 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2021
- Study start8 Mar 2022
- Primary completion8 Nov 2027 (estimated)
- Study completion8 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CDKL5 Deficiency DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 87 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zogenix, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- UCB Cares, Study director, 001 844 599 2273
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05064878
- Sponsor's protocol ID
- ZX008-2103/EP0216
- Other IDs
- 2021-003222-76, 2023-506269-78-00, 2023
- Acronym
- GEMZ
- Status last verified
- Apr 2026
- First submitted
- 22 Sep 2021
- Last updated
- 29 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05064878
- Acronym / sponsor ID
- GEMZ / ZX008-2103/EP0216
- Conditions
- CDKL5 Deficiency Disorder, Generalized Tonic Clonic Seizure, Epileptic Spasm, Refractory Seizures
- Keywords
- CDD, CDKL5, fenfluramine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 87 participants (actual)
- Lead sponsor
- Zogenix, Inc.Industry (pharma, biotech, devices)
- Study start
- 8 Mar 2022 (actual)
- Primary completion
- 8 Nov 2027 (estimated)
- Study completion
- 8 Nov 2027 (estimated)
- First posted
- 1 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 3 Study to examine the efficacy and safety of ZX008 in children and adults with cyclin-dependent kinase like-5 (CDKL5) deficiency disorder (CDD).
Detailed description
This is an up to 3-part multicenter study: a double-blind, placebo-controlled part (Part 1) which includes Baseline Period (4 weeks), Titration Period (2 weeks), Maintenance Period (12 weeks) and Transition Period (2 weeks), followed by up to 2 open-label extension (OLE) parts: Part 2 of 54 weeks [Treatment Period (52 weeks), Taper Period (2 weeks)] and Part 3, i.e., OLE1 and OLE2, respectively, with the addition of the second OLE part (Part 3/OLE2) only for participants who will continue on fenfluramine and have no alternative treatment access from another source (e.g., a managed access program [MAP]). Participants can remain in Part 3 until MAP access or approval of fenfluramine (ZX008) has been obtained from regulatory authorities for CDD in the participant's country of residence, or until the investigational product development for CDD is stopped by the Sponsor, whichever comes first. Participants who discontinue early from Part 1, Part 2, or Part 3 will attend a Cardiac Follow-Up Visit 6 months after their last dose of study drug.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Fenfluramine (hydrochloride) 0.8 mg/kg/day | Experimental | Drug: FenfluraminePart 1: Fenfluramine (hydrochloride) 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 | Placebo comparator | Drug: PlaceboPart 1: Matching fenfluramine (hydrochloride) placebo will be administered twice a day (BID) in equally divided doses with or without food. |
| Fenfluramine (hydrochloride) Open-label | Experimental | Drug: FenfluraminePart 2 and Part 3: Open-label fenfluramine (hydrochloride) will be administered using a flexible dosing regimen, up to fenfluramine 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]). Fenfluramine (hydrochloride) will be administered twice a day (BID) in equally divided doses with or without food. |
Who may qualify
- Ages
- 1 year to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Subject has a confirmed pathogenic or likely pathogenic mutation in the CDKL5 gene and a clinical diagnosis of CDKL5 deficiency disorder (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 antiepileptic treatments (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.
Key exclusion criteria (11 listed)
- 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 current eating disorder that suggests anorexia nervosa or bulimia.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FenfluramineAlso: FINTEPLA, ZX008, fenfluramine HCl, fenfluramine hydrochlorideFenfluramine is supplied as an oral aqueous solution of fenfluramine hydrochloride. | Drug | Fenfluramine (hydrochloride) 0.8 mg/kg/day, Fenfluramine (hydrochloride) Open-label |
| PlaceboMatching fenfluramine (hydrochloride) placebo is supplied as an oral solution. | Drug | Placebo |
Primary outcome
Percentage Change from Baseline in Countable Motor Seizure Frequency (CMSF) (Part 1)
Time frame: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
The median percentage change from the Baseline in monthly (per 28 days) CMSF during the combined Titration and Maintenance Periods with the fenfluramine (ZX008) 0.8 mg/kg/day group compared with the placebo group will be reported.
Percentage of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 2)
Time frame: Up to OLE1 Treatment Period Post-Dose Safety Follow-up Visit 17 (up to 70 weeks)
An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Treatment Emergent Adverse Events (TEAEs) are defined as any AEs reported on or after the first dose of study medication.
Percentage of Participants With Abnormal Physical Examination Findings (Part 2)
Time frame: Up to End of Treatment (EoT)/Early Termination (ET) Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Abnormal findings of physical exam that is considered clinically significant by Principal Investigator (PI).
Percentage of Participants With Abnormal Neurological Examination Findings (Part 2)
Time frame: Up to EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Abnormal findings of neurological exam that is considered clinically significant by PI.
Percentage of Participants with Positive Response to Self-harm Question (Part 2)
Time frame: OLE1 Treatment Period Day 1 to OLE1 Treatment Period Post-Dose Safety Follow-up Visit 17 (up to 70 weeks)
Percentage of Participants with Increase in Valvular Regurgitation from Baseline (except absent to trace) (Part 2)
Time frame: Baseline (28 days), Cardiac Follow-up Visit 18 (up to 96 weeks)
Valvular regurgitation will be assessed using a 2-dimensional (2-D) Color Doppler Echocardiography (ECHO).
Percentage of Participants with Pulmonary Arterial Hypertension (PASP > 35 mmHg) at any Time During Treatment on Repeat Testing (Part 2)
Time frame: OLE1 Treatment Period Day 1 to EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Laboratory Parameters (Hematology) (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Laboratory Parameters (Hormones) (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Laboratory parameters (Chemistry) (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Laboratory Parameters (Urinalysis) (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Vital Signs (Blood pressure) (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Vital Signs (Heart rate) (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Vital Signs (Temperature) (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Vital Signs (Respiratory rate) (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Body Weight (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Change from Baseline in Tanner Staging (Part 2)
Time frame: Baseline (28 days), EoT/ET Visit 16 of OLE1 Treatment Period (up to 68 weeks)
Percentage of Participants with TEAEs (Part 3)
Time frame: Up to OLE2 Period Post-Dose Safety Follow-up (up to 200 weeks)
An AE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. Treatment Emergent Adverse Events are defined as any AEs reported on or after the first dose of study medication.
Change from Baseline in Height (Part 3)
Time frame: Baseline (28 days), OLE2 Period EoT/ET Visit 23 (up to 198 weeks)
Change from Baseline in Body Weight (Part 3)
Time frame: Baseline (28 days), OLE2 Period EoT/ET Visit 23 (up to 198 weeks)
Percentage of Participants with Increase in Valvular Regurgitation from Baseline (except absent to trace) (Part 3)
Time frame: Baseline (28 days), Cardiac Follow-up Visit (up to 295 weeks)
Valvular regurgitation will be assessed using a 2 D Color Doppler ECHO.
Percentage of Participants with Pulmonary Arterial Hypertension (PASP > 35 mmHg) at any Time During Treatment on Repeat Testing (Part 3)
Time frame: OLE2 Period Day 1 to EoT/ET Visit 23 of OLE2 Period (up to 198 weeks)
35 secondary outcomes
Percentage of Participants Who Achieve a ≥ 50% Reduction from Baseline in CMSF (Part 1)
Time frame: Baseline (28 days), Combined T+M Periods (14 weeks)
Percentage of Participants with a Clinical Global Impression-Improvement (CGI-I) Rating of 'Much Improved' or 'Very Much Improved' as Assessed by Investigator (Part 1)
Time frame: At the end of the combined T+M Periods (14 weeks)
Percentage Change From Baseline in Monthly Generalized Tonic-Clonic (GTC) Seizure Frequency (Part 1)
Time frame: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
Categorized Percentage Change in Seizures from Baseline in CMSF (Part 1)
Time frame: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
Percentage of Participants who Achieve "Near Seizure Freedom" (Part 1)
Time frame: Combined T+M Periods (14 weeks)
Percentage of Participants with a CGI-I Rating of 'Much Improved' or 'Very Much Improved' as Assessed by the Parent/Caregiver (Part 1)
Time frame: At the end of the combined T+M Periods (14 weeks)
Percentage of Participants with Improvement (Minimal, Much or Very Much Improved) on the CGI-I Rating as Assessed, Independently, by the Investigator (Part 1)
Time frame: At the end of the combined T+M Periods (14 weeks)
Percentage of Participants with Improvement (Minimal, Much or Very Much Improved) on the CGI-I Rating as Assessed, Independently, by the Parent/Caregiver (Part 1)
Time frame: At the end of the combined T+M Periods (14 weeks)
Percentage Change from Baseline in the Monthly Frequency of all Seizures (Part 1)
Time frame: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
Change from Baseline in the Monthly Frequency of Countable Motor Seizure (CMS)-free Days (Part 1)
Time frame: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)
Percentage of Participants with TEAEs (Part 1)
Time frame: From Day of first dose to the End of the Maintenance Periods (up to 14 weeks)
Percentage of Participants With Abnormal Physical Examination Findings (Part 1)
Time frame: Baseline, Visit 6 (Day 43), Visit 7 (Day 71), Visit 8 (Day 99)
Percentage of Participants With Abnormal Neurological Examination Findings (Part 1)
Time frame: Baseline, Visit 6 (Day 43), Visit 8 (Day 99)
Percentage of Participants with Positive Response to Self-harm question (Part 1)
Time frame: Baseline, Visit 5 (Day 15), Visit 6 (Day 43), Visit 7 (Day 71), Visit 8 (Day 99)
Percentage of Participants with Increase in Valvular Regurgitation from Baseline (except absent to trace) (Part 1)
Time frame: From Day of first dose to the End of the Maintenance Period (up to 14 weeks)
Percentage of Participants with Pulmonary Arterial Hypertension (PASP > 35 mmHg) at any Time During Treatment on Repeat Testing (Part 1)
Time frame: From Day of first dose to the End of the Maintenance Period (up to 14 weeks)
Change from Baseline in Laboratory parameters (Hematology) (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Laboratory parameters (Hormones) (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Laboratory parameters (Chemistry) (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Laboratory Parameters (Urinalysis) (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Vital signs (Blood pressure) (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Vital signs (Heart rate) (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Vital signs (Temperature) (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Vital signs (Respiratory rate) (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Body Weight (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Change from Baseline in Tanner Staging (Part 1)
Time frame: Baseline (28 days), end of the combined Titration and Maintenance (T+M) Periods (Day 99)
Percentage Change from Baseline in CMSF (Part 2)
Time frame: Baseline (28 days), OLE1 Treatment Period (up to 52 weeks)
Categorized Percentage Change in Seizures from Baseline in CMSF (Part 2)
Time frame: Baseline (28 days), OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants who Achieve "Near Seizure Freedom" (Part 2)
Time frame: OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants with a CGI-I Rating of 'Much or Very Much Improved' as Assessed by the Investigator (Part 2)
Time frame: At the End of the OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants with a CGI-I Rating of 'Much or Very Much Improved' as Assessed by the Parent/Caregiver (Part 2)
Time frame: At the End of the OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants with Improvement (Minimal, Much or Very Much Improved) on the CGI-I Rating as Assessed, Independently, by the Investigator (Part 2)
Time frame: At the End of the OLE1 Treatment Period (up to 52 weeks)
Percentage of Participants with Improvement (Minimal, Much or Very Much Improved) on the CGI-I Rating as Assessed by the Parent/Caregiver (Part 2)
Time frame: At the End of the OLE1 Treatment Period (up to 52 weeks)
Percentage Change from Baseline in Monthly GTC Seizure Frequency (Part 2)
Time frame: Baseline (28 days), OLE1 Treatment Period (up to 52 weeks)
Change from Baseline in the Monthly Frequency of CMS-free Days (Part 2)
Time frame: Baseline (28 days), OLE1 Treatment Period (up to 52 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
UCB Cares study director
001 844 599 2273
46 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Fenfluramine in people with CDKL5 Deficiency Disorder and Generalized Tonic Clonic Seizure, run by Zogenix, Inc. at 46 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 46 sites in United States, Italy, Germany, Japan, United Kingdom and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage Change from Baseline in Countable Motor Seizure Frequency (CMSF) (Part 1) (time frame: Baseline (28 days), Combined Titration and Maintenance (T+M) Periods (14 weeks)). The study lists 22 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2026.