Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   40115   clinical trials with a EudraCT protocol, of which   6570   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2017-002628-26
    Sponsor's Protocol Code Number:ZX008-1601
    National Competent Authority:Belgium - FPS Health-DGM
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2018-03-30
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedBelgium - FPS Health-DGM
    A.2EudraCT number2017-002628-26
    A.3Full title of the trial
    A Two-Part Study of ZX008 in Children and Adults with
    Lennox-Gastaut Syndrome (LGS); Part 1: A Randomized,
    Double-blind, Placebo-controlled Trial of Two Fixed Doses
    of ZX008 (Fenfluramine Hydrochloride) Oral Solution as
    Adjunctive Therapy for Seizures in Children and Adults with
    LGS, Followed by Part 2: An Open-label Extension to
    Assess Long-Term Safety of ZX008 in Children and Adults
    with LGS
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Two-Part Study of ZX008 in Children and Adults with
    Lennox-Gastaut Syndrome (LGS); Part 1: A Randomized,
    Double-blind, Placebo-controlled Trial of Two Fixed Doses
    of ZX008 (Fenfluramine Hydrochloride) Oral Solution as
    Adjunctive Therapy for Seizures in Children and Adults with
    LGS, Followed by Part 2: An Open-label Extension to
    Assess Long-Term Safety of ZX008 in Children and Adults
    with LGS
    A.4.1Sponsor's protocol code numberZX008-1601
    A.5.4Other Identifiers
    Name:INDNumber:132604
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorZogenix International Limited, a wholly owned subsidiary of Zogenix Inc.
    B.1.3.4CountryUnited Kingdom
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportZogenix International Limited
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationSyneos Health
    B.5.2Functional name of contact pointJohn Elie, Associate PD
    B.5.3 Address:
    B.5.3.1Street Address1030 Sync Street
    B.5.3.2Town/ cityMorrisville
    B.5.3.3Post codeNC 27560
    B.5.3.4CountryUnited States
    B.5.4Telephone number19197452667
    B.5.6E-mailjohn.elie@syneoshealth.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/17/1836
    D.3 Description of the IMP
    D.3.1Product nameFENFLURAMINE HYDROCHLORIDE
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFenfluramine
    D.3.9.1CAS number 404-82-0
    D.3.9.2Current sponsor codeZX008
    D.3.9.3Other descriptive nameFenfluramine HCl, DL-Fenfluramine, (±)-Fenfluramine
    D.3.9.4EV Substance CodeSUB02115MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/17/1836
    D.3 Description of the IMP
    D.3.1Product nameFENFLURAMINE HYDROCHLORIDE
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFenfluramine
    D.3.9.1CAS number 404-82-0
    D.3.9.2Current sponsor codeZX008
    D.3.9.3Other descriptive nameFenfluramine HCl, DL-Fenfluramine, (±)-Fenfluramine
    D.3.9.4EV Substance CodeSUB02115MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number2.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/17/1836
    D.3 Description of the IMP
    D.3.1Product nameFENFLURAMINE HYDROCHLORIDE
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNFenfluramine
    D.3.9.1CAS number 404-82-0
    D.3.9.2Current sponsor codeZX008
    D.3.9.3Other descriptive nameFenfluramine HCl, DL-Fenfluramine, (±)-Fenfluramine
    D.3.9.4EV Substance CodeSUB02115MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typeup to
    D.3.10.3Concentration number1.25
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboOral solution
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Lennox-Gastaut Syndrome in Children and Adults
    E.1.1.1Medical condition in easily understood language
    NA
    E.1.1.2Therapeutic area Diseases [C] - Nervous System Diseases [C10]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10048816
    E.1.2Term Lennox-Gastaut syndrome
    E.1.2System Organ Class 10029205 - Nervous system disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    The primary objective of Part 1 is the primary objective of the entire study.
    The primary objective of Part 1 is:
    To evaluate the effect of ZX008 0.8 mg/kg/day versus placebo as adjunctive therapy for the treatment of uncontrolled seizures in children and adults with Lennox-Gastaut syndrome (LGS) based on the change in frequency of seizures that result in drops between baseline and the combined Titration and Maintenance Periods (T+M)
    The primary objective of Part 2 is to assess the long-term safety and tolerability of ZX008 in children and adults with LGS with regard to adverse events (AEs), laboratory parameters, physical examination, neurological examination, suicidality, cognition (BRIEF), vital signs (blood pressure, heart rate, temperature, and respiratory rate), electrocardiograms (ECG), echocardiograms (ECHO), body weight, and BMI.
    E.2.2Secondary objectives of the trial
    The key secondary objectives of Part 1 are:
    • To evaluate the effect of ZX008 0.2 mg/kg/day vs placebo as adjunctive therapy for the treatment of uncontrolled seizures in children and adults with LGS based on the change in frequency of seizures that result in drops between baseline and T+M
    • To evaluate the effect of ZX008 0.2 and 0.8 mg/kg/day (independently) versus placebo on the proportion of subjects who achieve a ≥50% reduction from Baseline in the frequency of seizures taht result in drops.
    • To evaluate the effect of ZX008 0.2 and 0.8 mg/kg/day (independently) versus placebo on the Clinical Global Impression – Improvement rating, as assessed by the Principal Investigator.
    In order to review the secondary objectives of Part 2 please refer to the section 2.2.2. of the protocol amendment 2.1 dated 29 July 2019.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Subject is male or nonpregnant, nonlactating female, age 2 to 35
    years, inclusive as of the day of the Screening Visit. Female subjects of
    childbearing potential must not be pregnant or breast-feeding. Female
    subjects of childbearing potential must have a negative urine or serum
    pregnancy test at screening. Subjects of childbearing or childfathering
    potential must be willing to use medically acceptable forms of birth
    control, which includes abstinence, while being treated on this study and
    for 90 days after the last dose of study drug
    2. Subject must have a diagnosis of LGS, where seizures that result in
    drops are not completely controlled by current antiepileptic treatments.
    (Subjects without a formal diagnosis may still be enrolled at Sponsor
    discretion if all other criteria are met)
    3.Subjects must meet all of the following 4 criteria for GLS, as defined in
    this protocol:
    a.Onset of seizures at 11 years of age or younger
    b.Multiple seizure types (must include TS or TA), including countable
    motor seizures that result in drops. Countable motor seizure types
    eligible for inclusion are: GTC, TS, CS, AS, FS with observable motor
    symptoms, and MS that result in a drop
    c.Abnormal cognitive development
    d.Evidence of EEG in the medical history that shows abnormal
    background activity accompanied by slow spike and wave pattern <2.5
    Hz(Acceptable evidence includes a copy of the EEG trace, EEG report, or
    physician note that appropriately describes the EEG findings.)
    4.Subject must have had at least 8 drop seizures in the last 4 weeks
    prior to Screening (minimum of 4 drop seizures in the first two weeks
    and 4 in the last two weeks before baseline), by parent/guardian report
    to Investigator or investigator medical notes
    5.Receiving at least 1 concomitant AED and up to 4 concomitant AEDs,
    inclusive. The KD and VNS are permitted but do not count towards the
    total number of AEDs. Rescue medications for seizures are not counted
    towards the total number of AEDs
    6.All medications or interventions for epilepsy (including KD and VNS)
    must be stable for at least 4 weeks prior to screening and are expected
    to remain stable throughout the study
    7.Subject has been informed of the nature of the study and informed
    consent has been obtained from the legally responsible parent/guardian.
    8.Subject has provided assent in accordance with Institutional Review
    Board (IRB)/Ethics Committee requirements, if capable
    9.Subject's parent/caregiver is willing and able to be compliant with
    diary completion, visit schedule and study drug accountability
    Randomization:
    1.Subject has been approved for study inclusion by the Epilepsy Study
    Consortium
    2.Subject does not have an exclusionary cardiovascular or
    cardiopulmonary abnormality
    based on ECHO, ECG or physical examination and is approved for entry
    by the central cardiac reader. Exclusionary abnormalities include, but are
    not limited to:
    a.Trace or greater mitral or aortic valve regurgitation in subjects <18
    years of age
    b.Mild or greater mitral or aortic valve regurgitation in subjects >18
    years of age
    c.Possible signs of pulmonary hypertension with abnormal or greater
    than upper range of normal values
    d.Evidence of left ventricular dysfunction (systolic or diastolic)
    3.Subject demonstrates a stable baseline with ≥ 2 seizures per week
    resulting in drops during the 4-week Baseline Period
    4.Subject's parent/caregiver has been compliant with diary completion
    during the Baseline Period, in the opinion of the Investigator and Sponsor.
    E.4Principal exclusion criteria
    1. Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication.
    2. Subject’s etiology of seizures is a degenerative neurological disease.
    3. Subject has a history of hemiclonic seizures in the first year of life.
    4. Subject only has drop seizures in clusters, where individual seizures cannot be counted reliably.
    5. Subject has pulmonary arterial hypertension.
    6. Subject has current or past history of cardiovascular or cerebrovascular disease, such as cardiac valvulopathy, myocardial infarction or stroke, or clinically significant structural cardiac abnormality, including but not limited to mitral valve prolapse, atrial or ventricular septal defects, patent ductus arteriosis (note: Patent Foramen Ovale or a bicuspid valve are not considered exclusionary).
    7. Subject has current or recent history of Anorexia Nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month.
    8. Subject has a current or past history of glaucoma.
    9. Subject has had an anoxic episode requiring resuscitation within 6 months of the Screening Visit.
    10. Subject has moderate or severe hepatic impairment. Asymptomatic subjects with mild hepatic impairment (elevated liver enzymes < 3x ULN and/or elevated bilirubin <2x ULN) may be entered into the study after review and approval by the Medical Monitor in conjunction with the sponsor, in consideration of comorbidities and concomitant medications.
    11. Subject has severe renal impairment (estimated glomerlular filtration rate <30mL/min/1.73m2)
    12. 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 atomexetine; or cyproheptadine (see Appendix 1 for a complete list of prohibited medications). (Note: Short-term medication requirements for prohibted medications will be handled on a per case basis by the Medical Monitor.)
    13. Subject has positive result on urine tetrahydrocannabinol (THC) Panel or whole blood cannabidiol (CBD) at the Screening Visit.
    14. Subject is taking felbamate for less than 1 year prior to screening and/or does not have stable liver function and hematology laboratory tests, and/or the dose has not been stable for at least 60 days prior to the Screening Visit.
    15. Subject is known to be human immunodeficiency virus (HIV) positive.
    16. Subject is known to have active viral hepatitis (B or C)
    17. Subject is currently receiving an investigational product.
    18. Subject has participated in another clinical trial within the past 30 days (calculated from that study’s last scheduled visit). Participation in non-treatment trials will be reviewed by the medical monitor.
    19. Subject is at imminent risk of self-harm or harm to others, in the investigator’s opinion, based on clinical interview and responses provided on the Columbia-Suicide Severity Rating Scale (C-SSRS). Subjects must be excluded if they report suicidal behavior in the past 6 months as measured by the C-SSRS at Screening or Baseline, which includes suicidal ideation with intent and plan (Item #5). If a subject reports suicidal ideation on Item 4 without specific plan, and the investigator feels that the subject is appropriate for the study considering the potential risks, the investigator must document appropriateness for inclusion, and discuss with the parent/caregiver to be alert to mood or behavioral changes, especially around times of dose adjustment.
    20. Subject is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
    21. Subject is institutionalized in a general nursing home (ie, in a facility that does not provide skilled epilepsy care).
    22. Subject does not have a reliable caregiver who can provide seizure diary information throughout the study.
    23. Subject has a clinically significant condition, including chronic obstructive pulmonary disease, interstitial lung disease, or portal hypertension, or has had clinically relevant symptoms or a clinically significant illness 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.
    E.5 End points
    E.5.1Primary end point(s)
    Efficacy endpoints Part 1:
    • Percent change from baseline in the frequency of seizures that result
    in drops in the combined Titration and Maintenance Periods (T+M) in the
    ZX008 0.8 mg/kg/day group compared to the placebo group.
    Efficacy endpoints Part 2:
    • The change from baseline in the frequency of seizures that result in
    drops.
    • The change from baseline in the frequency of all countable motor
    seizures (GTC, TS, CS,
    AS, TA, FS, MS with a drop)
    • The change from baseline in the frequency of all countable seizures
    • The proportion of subjects who achieve a worsening from baseline (ie,
    <= 0% reduction),
    or >0%, ≥ 25%, ≥ 50%, ≥ 75%, 100% reduction, and "near seizure
    freedom" (ie, 0 or 1 seizures) from baseline in frequency of all countable
    seizures that result in drops, countable motor seizures that do not result
    in drops, all countable motor seizures, all countable seizures, and all
    countable seizures that do not result in drops
    • Number of seizure-free days, defined as 1) days with no countable
    seizures and 2) days with no seizures that result in drops
    • Longest interval between seizures that result in drops
    • Clinical Global Impression – Improvement rating, as assessed by the
    Principal Investigator.
    • Clinical Global Impression – Improvement rating, as assessed by the
    parent/caregiver.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Data from Part 1 will constitute the primary analyses of the study and will be performed upon database lock after the last subject enrolled has completed the last study visit of Part 1.
    The frequency of seizures that result in drops during the Part 2 OLE Treatment Period will be compared to baseline frequency measured prior to randomization in Part 1. Both the mean and median change from baseline will be presented and the statistical significance of the change will be assessed using a Wilcoxon signed-rank test. Other secondary assessments will be compared to baseline from prior to Part 1, or by visit throughout Part 1 and Part 2, as appropriate.
    E.5.2Secondary end point(s)
    • Change from baseline in the frequency of seizures that result in drops
    in T+M in the ZX008 0.2 mg/kg/day group compared to the placebo
    group.
    • Proportion of subjects who achieve a ≥50% reduction from baseline in
    the frequency of seizures that result in drops comparing the ZX008 0.8
    mg/kg/day and 0.2 mg/kg/day groups independently versus placebo
    • Proportion of subjects who achieve clinically-meaningful improvement
    (much or very much improved) in the Clinical Global Impression –
    Improvement as assessed by Principal Investigator comparing the
    ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups independently
    versus placebo.
    Additional Secondary Endpoints:
    ZX008 0.8 mg/kg/day and 0.2 mg/kg/day groups compared
    independently versus placebo on the
    • Change from baseline in the frequency of all countable motor seizures
    in T+M
    o Countable seizures include: generalized tonic-clonic seizures [GTC],
    tonic
    seizures [TS], clonic seizures [CS], atonic seizures [AS], tonic/atonic
    seizures
    [TA], clearly recognizable focal seizures [FS], and myoclonic seizures
    [MS] that
    result in a drop
    • Change from baseline in the frequency of countable seizures that
    result in drops
    • Change from baseline in the frequency of seizures that result in drops
    between baseline
    and the Maintenance Period (M)
    • Change from baseline in the frequency of countable seizures that do
    not result in drops
    • Proportion of subjects who achieve a worsening from baseline (ie, ≤
    0% reduction), or >0% , ≥25%, ≥50%, ≥75%, 100% reduction, and
    "near seizure freedom" (ie, 0 or 1 seizures) between baseline and T+M,
    and baseline and M, in all countable motor seizures; in countable motor
    seizures that do not result in drops; in all countable seizures; in all
    countable seizures that do not result in drops; and in all seizures that
    result in drops
    • Number of seizure-free days in the baseline, M, and T+M period,
    defined as 1) days with
    no countable seizures and 2) days with no seizures that result in drops
    • The longest interval (days) between seizures that result in drops
    comparing the ZX008
    0.8 mg/kg/day and 0.2 mg/kg/day groups independently versus
    placebo
    • Clinical Global Impression – Improvement as assessed by
    parent/caregiver
    The efficacy endpoints for Part 2 of the study are:
    • The change from baseline in the frequency of seizures that result in
    drops.
    E.5.2.1Timepoint(s) of evaluation of this end point
    NA
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic Yes
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned3
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA41
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Australia
    Austria
    Belgium
    Canada
    Denmark
    Finland
    France
    Germany
    Ireland
    Israel
    Italy
    Japan
    Mexico
    Netherlands
    Norway
    Poland
    Spain
    Sweden
    Switzerland
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    E.8.9.2In all countries concerned by the trial months11
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 250
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 150
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 98
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 92
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Parent or Legal Guardian will sign Consent in case Adult patients will be incapable to give a consent
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 122
    F.4.2.2In the whole clinical trial 250
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Follow-up cardiovascular safety assessments, including ECG and ECHO, will be performed 3-6 months following the last dose of study medication for all subjects, regardless of whether they complete the entire study or terminate early, unless the subject was known to be taking placebo (ie, blind was broken or subject was in Part 2). If the drug is not approved by the end of open label portion of the study, Sponsor will amend the open label portion of the study to extend the study duration.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-04-25
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-07-23
    P. End of Trial
    P.End of Trial StatusCompleted
    The status of studies in GB is no longer updated from 1.1.2021
    For the UK, as from 1.1.2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2021 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA