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    Summary
    EudraCT Number:2018-003980-77
    Sponsor's Protocol Code Number:DEN-315
    Clinical Trial Type:Outside EU/EEA
    Date on which this record was first entered in the EudraCT database:2018-12-13
    Trial results View 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
    H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED
    Expand All   Collapse All
    A. Protocol Information
    A.2EudraCT number2018-003980-77
    A.3Full title of the trial
    A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial to Investigate the Immunogenicity and Safety of Subcutaneous Administration of a Tetravalent Dengue Vaccine Candidate in Healthy Adolescent Subjects in Non-Endemic Area(s) for Dengue
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Trial to Investigate Immunogenicity and Safety of TDV in Healthy Children in Non-Endemic Area(s)
    A.4.1Sponsor's protocol code numberDEN-315
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03341637
    A.5.3WHO Universal Trial Reference Number (UTRN)U1111-1192-7827
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/180/2017
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorTakeda Vaccines, Inc.
    B.1.3.4CountryUnited States
    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 supportTakeda Vaccines, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationTakeda Vaccines, Inc.
    B.5.2Functional name of contact pointShibadas Biswal
    B.5.3 Address:
    B.5.3.1Street Address40 Landsdowne Street
    B.5.3.2Town/ cityCambridge
    B.5.3.3Post codeMA 02139
    B.5.3.4CountryUnited States
    B.5.4Telephone number+6568089724
    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 No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameTetravalent Dengue Vaccine Candidate (TDV)
    D.3.2Product code TAK-003
    D.3.4Pharmaceutical form Powder and solvent for solution for injection
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPSubcutaneous use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTDV CHIMERIC DENGUE VIRUS SEROTYPE 1
    D.3.9.2Current sponsor codeTDV-1
    D.3.9.3Other descriptive nameTDV CHIMERIC DENGUE VIRUS SEROTYPE 1 (TDV-1)
    D.3.9.4EV Substance CodeSUB188351
    D.3.10 Strength
    D.3.10.1Concentration unit PFU/ml plaque forming unit(s)/millilitre
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number25178
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTDV DENGUE VIRUS SEROTYPE 2
    D.3.9.2Current sponsor codeTDV-2
    D.3.9.3Other descriptive nameTDV DENGUE VIRUS SEROTYPE 2 (TDV-2)
    D.3.9.4EV Substance CodeSUB188352
    D.3.10 Strength
    D.3.10.1Concentration unit PFU/ml plaque forming unit(s)/millilitre
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number7962
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTDV CHIMERIC DENGUE VIRUS SEROTYPE 3
    D.3.9.2Current sponsor codeTDV-3
    D.3.9.3Other descriptive nameTDV CHIMERIC DENGUE VIRUS SEROTYPE 3 (TDV-3)
    D.3.9.4EV Substance CodeSUB188353
    D.3.10 Strength
    D.3.10.1Concentration unit PFU/ml plaque forming unit(s)/millilitre
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number100236
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTDV CHIMERIC DENGUE VIRUS SEROTYPE 4
    D.3.9.2Current sponsor codeTDV-4
    D.3.9.3Other descriptive nameTDV CHIMERIC DENGUE VIRUS SEROTYPE 4 (TDV-4)
    D.3.9.4EV Substance CodeSUB188354
    D.3.10 Strength
    D.3.10.1Concentration unit PFU/ml plaque forming unit(s)/millilitre
    D.3.10.2Concentration typenot less then
    D.3.10.3Concentration number399052
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin No
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
    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) Yes
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Yes
    D.3.11.10Medicinal product containing genetically modified organisms Yes
    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 placeboSolution for injection
    D.8.4Route of administration of the placeboSubcutaneous use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    The purpose of this study is to describe the neutralizing antibody response against each dengue serotype at 1 month post second dose of TDV or placebo in dengue-naive adolescent participants.
    E.1.1.1Medical condition in easily understood language
    Dengue fever is caused by infection with dengue virus, a RNA virus that occurs as 4 recognized serotypes: DENV-1, -2, -3, or -4. These viruses are transmitted from human to human by mosquitoes.
    E.1.1.2Therapeutic area Diseases [C] - Virus Diseases [C02]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level LLT
    E.1.2Classification code 10012312
    E.1.2Term Dengue fever virus infection
    E.1.2System Organ Class 100000004862
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To describe the neutralizing antibody response against each dengue serotype at 1 month post second dose of TDV or placebo in dengue-naive adolescent subjects.
    E.2.2Secondary objectives of the trial
    Immunogenicity:
    • To describe the persistence of the immune response at 6 months post second dose of TDV or placebo in dengue-naive adolescent subjects.
    • To describe the seropositivity rates for all dengue serotypes at 1 month and 6 months post second dose of TDV or placebo in dengue-naive adolescent subjects, where seropositivity is defined as a reciprocal neutralizing titer ≥10.

    Safety:
    • To describe the safety profile following a first and second dose of TDV or placebo at Day 1
    (Month 0 [M0]) and Day 90 (Month 3 [M3]), respectively.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. The subject is aged 12 to 17 years, inclusive.
    2. Individuals who are in good health at the time of entry into the trial as determined by medical history, physical examination (including vital signs) and the clinical judgment of the Investigator.
    3. The subject/the subject’s legally authorized representative (LAR) signs and dates a written, informed consent/assent form and any required privacy authorization prior to the initiation of any trial procedures, after the nature of the trial has been explained according to local regulatory requirements. Assent is obtained from the subject where required.
    4. Individuals who can comply with trial procedures and are available for the duration of follow-up.
    E.4Principal exclusion criteria
    1. Individuals with an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination (consider whether applicable as an exclusion criterion or criterion for delay, see Section 7.3).
    2. Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccines or placebo).
    3. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the subject’s ability to participate in the trial.
    4. Individuals with any history of progressive or severe neurologic disorder, seizure disorder or neuro-inflammatory disease (eg, Guillain-Barré syndrome).
    5. Individuals with history or any illness that, in the opinion of the Investigator, might interfere with the results of the trial or pose additional risk to the subject due to participation in the trial.
    6. Known or suspected impairment/alteration of immune function, including:
    a.Chronic use of oral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (M0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
    b.Receipt of parenteral steroids (equivalent to 20 mg/day prednisone ≥12 weeks/≥ 2 mg/kg body weight/day prednisone ≥2 weeks) within 60 days prior to Day 1 (M0).
    c. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (M0) or planned administration during the trial.
    d.Receipt of immunostimulants within 60 days prior to Day 1 (M0).
    e. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within
    6 months prior to Day 1 (M0).
    f. Human immunodeficiency virus (HIV) infection or HIV-related disease.
    g.Genetic immunodeficiency.
    7. Abnormalities of splenic or thymic function.
    8. Individuals with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
    9. Individuals with any serious chronic or progressive disease according to judgment of the Investigator (eg, neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
    10. Individuals with body mass index (BMI) greater than or equal to 35 kg/m2 (=weight in kg/[height in meters2]).
    11. Individuals participating in any clinical trial with another investigational product 30 days prior to Day 1 (M0) or intent to participate in another clinical trial at any time during the conduct of this trial.
    12. Individuals who received any other vaccine within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this trial or who are planning to receive any vaccine within 28 days of trial vaccine administration.
    13. Individuals involved in the trial conduct or their first degree relatives.
    14. Individuals with history of substance or alcohol abuse within the past 2 years.
    15. Female subjects who are pregnant or breastfeeding.
    16. Females of childbearing potential who are sexually active, and who have not used any of the acceptable contraceptive methods for at least 2 months prior to Day 1 (M0).
    a. Of childbearing potential is defined as status post onset of menarche and not meeting any of the following conditions: bilateral tubal ligation (at least 1 year previously), bilateral oophorectomy (at least 1 year previously) or hysterectomy.
    b. Acceptable birth control methods are defined as one or more of the following:
    i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring).
    ii. Barrier method (condom with spermicide or diaphragm with spermicide) each and every time during intercourse.
    iii. Intrauterine device.
    iv. Monogamous relationship with vasectomized partner (partner must have been vasectomized for at least 6 months prior to Day 1 [M0]).
    Other contraceptive methods may be considered in agreement with the Sponsor and will be approved by the appropriate ethics committee.
    17. Females of childbearing potential who are sexually active, and who refuse to use an acceptable contraceptive method up to 6 weeks after the last dose of trial vaccine (Day 90 [M3]). In addition, they must be advised not to donate ova during this period.
    18. Any positive or indeterminate pregnancy test.
    19. Previous and planned vaccination (during the trial conduct), against any flaviviruses including dengue, yellow fever (YF), Japanese encephalitis (JE) viruses or tick-borne encephalitis.
    20. Previous participation in any clinical trial of a dengue or other flavivirus (eg, West Nile [WN] virus) candidate vaccine, except for subjects who received placebo in those trials.
    21. Subjects with documented or suspected disease caused by a flavivirus such as dengue, Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis.
    E.5 End points
    E.5.1Primary end point(s)
    Geometric mean titers (GMT) of neutralizing antibodies (microneutralization test 50% [MNT50]) for each of the 4 dengue serotypes at 1 month post second dose (Day 120 [Month 4 (M4)]).
    E.5.1.1Timepoint(s) of evaluation of this end point
    Time Frame: 1 month post second dose (Day 120)
    E.5.2Secondary end point(s)
    Immunogenicity:
    • GMTs of neutralizing antibodies (MNT50) for each of the 4 dengue serotypes at 6 months post second dose (Day 270 [M9]).
    • Seropositivity rates (% of subjects seropositive) for each of the 4 dengue serotypes at 1 month and 6 months post second dose (Day 120 [M4]) and Day 270 [M9], respectively).
    • Seropositivity rates (% of subjects seropositive) for multiple (2, 3, or 4) dengue serotypes at 1 month and 6 months post second dose (Day 120 [M4]) and Day 270 [M9], respectively).
    Note: Seropositivity is defined as a reciprocal neutralizing titer ≥10.

    Safety:
    • Frequency and severity of solicited local (injection site) adverse events (AE) for 7 days (day of vaccination+6 subsequent days) and solicited systemic AEs for 14 days (day of vaccination+13 subsequent days) after each TDV/placebo dose on Day 1 (M0) and Day 90 (M3).
    • Percentage of subjects with any unsolicited AEs for 28 days (day of vaccination+27 subsequent days) after each TDV/placebo dose on Day 1 (M0) and Day 90 (M3).
    • Percentage of subjects with medically attended AEs (MAAE) and serious adverse events (SAE) throughout the trial.
    E.5.2.1Timepoint(s) of evaluation of this end point
    Multiple time points occurring as stated in Section E.5.2
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy No
    E.6.4Safety Yes
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    Immunogenicity
    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 trial2
    E.8.3 Will this trial be conducted at a single site globally? No
    E.8.4 Will this trial be conducted at multiple sites globally? Yes
    E.8.6 Trial involving sites outside the EEA
    E.8.6.2Trial being conducted completely outside of the EEA Yes
    E.8.6.3Specify the countries outside of the EEA in which trial sites are planned
    Mexico
    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.8.9.2In all countries concerned by the trial months9
    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: 400
    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) No
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 400
    F.1.2Adults (18-64 years) No
    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 Yes
    F.3.2Patients No
    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 No
    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
    Children between 12 and 17 years of age.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.2 For a multinational trial
    F.4.2.2In the whole clinical trial 400
    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)
    None
    G. Investigator Networks to be involved in the Trial
    H.4 Third Country in which the Trial was first authorised
    H.4.1Third Country in which the trial was first authorised: Mexico
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