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A Study to Examine the Efficacy and Safety of ZX008 in Subjects with CDKL5 Deficiency Disorder
EU CTIS ID: 2023-506269-78-00
What this study is testing
- To demonstrate that the efficacy of fenfluramine (ZX008) 0.8 mg/kg/day is superior to placebo as an adjunctive therapy for pediatric and adult subjects with CDD (Part 1) - To characterize the long-term safety and tolerability of fenfluramine (ZX008) in pediatric and adult subjects with CDD (Part 2 and Part 3)
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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. Subjects aged 1 to < 2 years will ONLY be permitted to enroll in the trial AFTER the DSMB has determined that it is appropriate to do so based on a planned unblinded interim safety review to be conducted after approximately 40 subjects aged ≥ 2 to 35 years have completed Visit 6.
- 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). During the trial, rescue medications or interventions for rescue treatment of seizures will not be counted towards the total number of antiseizure treatments established at Baseline.
- 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. In order to establish stability at BL, duration of treatment with medications or interventions for epilepsy prior to the Screening visit must be as follows: VNS and RNS: ≥ 6 months duration; ASMs or KD: ≥ 4 weeks duration.
- At the Screening Visit, parent/caregiver reports that subject has ≥ 4 countable motor seizures (CMS) per week. CMS include distinct seizures of the generalized tonic-clonic [GTC], bilateral clonic, bilateral tonic, atonic (drop), bilateral tonic/atonic (drop), or focal to bilateral tonicclonic type lasting approximately 3 seconds or longer, to distinguish from short-clustered seizures, spasms, or jerks.
You likely can't join if
- Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study drug.
- 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.
- Subject is taking > 4 concomitant ASMs. Rescue medications are not included in the count.
See the full eligibility criteria
Who can join
- 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. Subjects aged 1 to < 2 years will ONLY be permitted to enroll in the trial AFTER the DSMB has determined that it is appropriate to do so based on a planned unblinded interim safety review to be conducted after approximately 40 subjects aged ≥ 2 to 35 years have completed Visit 6.
- 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). During the trial, rescue medications or interventions for rescue treatment of seizures will not be counted towards the total number of antiseizure treatments established at Baseline.
- 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. In order to establish stability at BL, duration of treatment with medications or interventions for epilepsy prior to the Screening visit must be as follows: VNS and RNS: ≥ 6 months duration; ASMs or KD: ≥ 4 weeks duration.
- At the Screening Visit, parent/caregiver reports that subject has ≥ 4 countable motor seizures (CMS) per week. CMS include distinct seizures of the generalized tonic-clonic [GTC], bilateral clonic, bilateral tonic, atonic (drop), bilateral tonic/atonic (drop), or focal to bilateral tonicclonic type lasting approximately 3 seconds or longer, to distinguish from short-clustered seizures, spasms, or jerks.
- Subject (and/or subject's parent[s]/legal guardian[s]) has provided written informed consent (and assent if applicable).
- Subject (and/or subject's parent/caregiver) is willing and able to comply with study requirements (including diary completion, visit schedule, and study drug accountability).
What rules you out
- Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study drug.
- 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.
- 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. Disallowed medications are subject to wash-out requirements.
- Subject has moderate to severe hepatic impairment, assessed based on the Child-Pugh system.
- Subject has previously been treated with Fintepla® (fenfluramine) prior to the Screening Visit.
- Subject has moderate to severe renal impairment (estimated glomerular filtration rate < 50 mL/min/1.73 m2 calculated with the Isotope Dilution Mass Spectrometry [IDMS] Traceable Schwartz equation for children and the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation for adults, using actual body weight).
- Subject is receiving concomitant therapy with any of the following: centrally-acting anorectic agents; monoamine-oxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; other centrally-acting noradrenergic agonists, including atomoxetine; or cyproheptadine. (Note: Short-term requirements for prohibited medications will be handled on a per case basis by the Medical Monitor.)
- 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.
- Female subjects of childbearing potential must not be pregnant or breastfeeding. Female subjects of childbearing potential must have a negative urine or serum pregnancy test at Screening. Subjects of childbearing or child-fathering potential must be willing to use an approved method of highly effective contraception, which includes abstinence, while participating in this study and for 90 days after the last dose of study drug.
- Subject is known to be human immunodeficiency virus positive.
- Subject is known to have active viral hepatitis B or C.
- Subject is institutionalized in a facility that does not provide skilled epilepsy care.
- Subject has a diagnosis of pulmonary arterial hypertension.
The study team makes the final eligibility decision.
Where it's taking place
- Israel
- United Kingdom
- United Arab Emirates
- Japan
- United States
- Georgia
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years, 0-17 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Israel; United Kingdom; United Arab Emirates; Japan; United States; Georgia. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.