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Healthy VolunteersPhase 3NCT03525119

Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) Co-administered With an Hepatitis A Virus Vaccine

A Phase 3 study testing TDV and HAV Vaccine in people with Healthy Volunteers, run by Takeda at 10 sites in United Kingdom.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to investigate the immunogenicity and safety of the concomitant administration of TDV (subcutaneous [SC] injection) and of hepatitis A virus (HAV) vaccine (intramuscular [IM] injection) in healthy participants aged 18 to 60 years living in country(ies) non-endemic for both dengue and… Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Healthy Volunteers
What is being tested?
TDV and HAV Vaccine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
900 participants
Where
10 sitesUnited Kingdom
Study dates
16 May 2018to 9 Jul 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

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 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • The participant is aged 18 to 60 years, inclusive.
  • Participants 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.
  • The participant signs and dates a written informed consent 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.
  • Participants who can comply with trial procedures and are available for the duration of follow-up.

Who cannot join

  • Participants with an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination.
  • Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccines or placebo).
  • Participants with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the participant's ability to participate in the trial.
  • Participants with any history of progressive or severe neurologic disorder, seizure disorder orneuro-inflammatory disease (eg, Guillain-Barré syndrome).
  • Participants 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 participant due to participation in the trial.
  • Known or suspected impairment/alteration of immune function, including:
Show all 38Show fewer
  • 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 (Month 0) (use of inhaled, intranasal, or topical corticosteroids is allowed).
  • 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 (Month 0).
  • Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial.
  • Receipt of immunostimulants within 60 days prior to Day 1 (Month 0).
  • Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
  • Human immunodeficiency virus (HIV) infection or HIV-related disease.
  • Hepatitis A virus (HAV) infection.
  • Hepatitis C virus infection.
  • Genetic immunodeficiency.
  • Abnormalities of splenic or thymic function.
  • Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
  • Participants with any serious chronic or progressive disease according to judgment of the Investigator (eg, neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
  • Participants with body mass index (BMI) greater than or equal to 35 kg/m^2 (=weight in kg/[height in meters^2]).
  • Participants participating in any clinical trial with another investigational product 30 days prior to Day 1 (Month 0) or intent to participate in another clinical trial at any time during the conduct of this trial.
  • Participants 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.
  • Previous HAV vaccination (in a clinical trial or with an approved product).
  • Participants involved in the trial conduct or their first degree relatives.
  • Participants with history of substance or alcohol abuse within the past 2 years.
  • Female participants who are pregnant or breastfeeding.
  • 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 (Month 0).
  • 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
  • Acceptable birth control methods are defined as one or more of the following:
  • Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring).
  • Barrier method (condom with spermicide or diaphragm with spermicide) each and every time during intercourse.
  • Intrauterine device (IUD). iv. Monogamous relationship with vasectomized partner (partner must have been vasectomized for at least 6 months prior to Day 1 [Month 0]).
  • Other contraceptive methods may be considered in agreement with the Sponsor and implemented only after approval of a substantial amendment by the regulatory authorities and by the appropriate ethics committee.
  • 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.
  • Any positive or indeterminate pregnancy test.
  • Previous and planned vaccination (during the trial conduct) against any flaviviruses including dengue, yellow fever (YF), Japanese Encephalitis (JE) viruses or tick-borne encephalitis.
  • Previous participation in any clinical trial of a dengue or other flavivirus (eg, West Nile [WN] virus) candidate vaccine, except for participants who received placebo in those trials.
  • Participants with a current or previous infection with a flavivirus such as dengue, Zika, YF, JE, WN fever, tick-borne encephalitis or Murray Valley encephalitis and participants with a history of prolonged (≥1 year) habitation in a dengue endemic area.
  • Participants with contraindications, warnings and/or precautions to vaccination with the HAV vaccine as specified within the product information.

Trial locations and contacts

10 sites in 1 country.

10 sites in 1 country

United Kingdom10 sites

  • Synexus - Wales

    Cardiff, CF15 9SS

  • Synexus - Lancashire

    Chorley, Lancashire, PR7 7NA

  • Synexus - Midlands

    Edgbaston, Birmingham, B15 2SQ

  • Synexus - Scotland

    Glasgow, G20 0SP

  • North East Clinical Research Centre, Hexham General Hospital

    Hexham, NE46 1QJ

  • Synexus - Manchester

    Manchester, M15 6SX

  • Synexus - Thames Valley

    Reading, RG2 0TG

  • Royal Hallamshire Hospital

    Sheffield, Yorkshire, S10 2JF

  • North Tees Clinical Research Centre, Middlefield Centre, University Hospital of North Tees

    Stockton-on-Tees, TS19 8PE

  • Synexus - Merseyside

    Waterloo, Liverpool, L22 0LG

Other trials in United Kingdom

About this study

Official title: A Randomized, Observer Blind, Phase 3 Trial to Investigate the Immunogenicity and Safety of the Co-administration of a Subcutaneous Tetravalent Dengue Vaccine Candidate (TDV) and an Intramuscular Hepatitis A Virus (Inactivated) Vaccine in Healthy Subjects Aged 18 to 60 Years in Non-endemic Country(Ies) for Dengue

The purpose of this study is to investigate the immunogenicity and safety of the concomitant administration of TDV (subcutaneous [SC] injection) and of hepatitis A virus (HAV) vaccine (intramuscular [IM] injection) in healthy participants aged 18 to 60 years living in country(ies) non-endemic for both dengue and hepatitis.

Read the detailed description

The vaccine tested in this study is TDV. TDV co-administered with HAV vaccine will be tested to assess immunogenicity and safety in healthy participants in non-endemic area(s) for dengue and HAV.

The study will enroll approximately 900 patients. Participants will be randomly assigned to one of the three groups-which will remain undisclosed to the observer. Participants will be randomized in 1:1:1 ratio to receive:

  • Group 1: HAV vaccine (IM) and TDV placebo-matching injection (SC), co-administered at Day 1 (Month 0 [M0]); TDV placebo-matching injection (SC) administered at Day 90 (Month 3 [M3])
  • Group 2: TDV (SC) and HAV placebo-matching injection (IM), co-administered at Day 1 (Month 0 [M0]); TDV (SC) administered at Day 90(Month 3 [M3])
  • Group 3: TDV (SC) and HAV vaccine (IM), co-administered at Day 1 (Month 0 [M0]); TDV (SC) administered at Day 90 (Month 3 [M3])

This multi-center trial will be conducted in United Kingdom. The overall time to participate in this study is 270 days. Participants will have multiple visits to the clinic with a 6-months follow up after the last study administration, including a final visit at Day 270.

Being tested
TDV, HAV Vaccine, TDV Placebo, HAV Vaccine Placebo
Keywords
Vaccine

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TDVBiological

    TDV SC injection

  • HAV VaccineBiological

    HAV Vaccine IM injection.

  • TDV PlaceboBiological

    Placebo-matching (normal saline (0.9% NaCl) SC injection.

  • HAV Vaccine PlaceboBiological

    Placebo-matching (normal saline (0.9% NaCl) IM injection.

Study groups in NCT03525119
Study groupRoleWhat they receive
HAV Vaccine 1.0 ml + Placebo/ PlaceboOtherHAV vaccine 1.0 ml, injection, IM, and placebo-matching injection, SC, once on Day 1 (first dose) followed by placebo-matching injection, SC on Day 90 (second dose).
Receives: Biological: HAV Vaccine; Biological: TDV Placebo
TDV 0.5 ml + Placebo/ TDV 0.5 mlExperimentalTDV 0.5 ml, injection, SC, and placebo-matching injection, IM, once on Day 1 (first dose) followed by TDV 0.5 ml, injection, SC on Day 90 (second dose).
Receives: Biological: TDV; Biological: HAV Vaccine Placebo
TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 mlExperimentalTDV 0.5 ml, injection, SC, and HAV vaccine 1.0 ml, injection, IM, once on Day 1 (first dose) followed by TDV 0.5 ml, injection, SC on Day 90 (second dose).
Receives: Biological: TDV; Biological: HAV Vaccine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants HAV/Dengue Virus (DENV)-Naive at Baseline Who Are Seroprotected Against HAV at Day 30

    Seroprotection is defined as serum anti-HAV antibody levels ≥12.5 mIU/mL, measured by enzyme-linked immunosorbent assay (ELISA). Immunological naivety to HAV/DENV is defined as anti-HAV antibody levels <12.5 mIU/mL and reciprocal neutralizing titers for all 4 dengue serotypes <10. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.

    Measured: One month post first vaccination (Day 30)

Secondary outcomes (8)

  1. Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 30 and Day 120 in Participants HAV/DENV-naive at Baseline

    GMTs of neutralizing antibodies were measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.

    Measured: One month post first vaccination (Day 30) and one month post second vaccination (Day 120)

  2. Percentage of Participants HAV/DENV-naive at Baseline Who Are Seropositive for Each of the 4 Dengue Serotypes at Day 30 and Day 120

    Seropositivity is defined as a reciprocal neutralizing titer ≥10. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.

    Measured: One month post first vaccination (Day 30) and one month post second vaccination (Day 120)

  3. Geometric Mean Concentrations (GMC) of Anti-HAV Antibodies at Day 30 in Participants HAV/DENV-naive at Baseline

    GMC of anti-HAV antibodies were measured by ELISA.

    Measured: One month post first vaccination (Day 30)

  4. Percentage of Participants With Solicited (Local Injection) Site Adverse Events (AEs) by Severity After Each Vaccination

    Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents daily activity with or without treatment), redness (erythema) (<2.5 cm, mild: 2.5-5 cm, moderate: >5 to <=10 cm, severe: >10 cm) and swelling (edema/induration) (<2.5 cm, mild: 2.5-5 cm, moderate: >5 to <=10 cm, severe: >10 cm ). The percentages were rounded off to the first decimal place.

    Measured: Within 7 days after each vaccination

  5. Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination

    Solicited systemic AEs include fever, headache, asthenia, malaise and myalgia that occurred within 14 days after each vaccination. Solicited systemic AEs (headache, asthenia, malaise and myalgia) was graded from 0 to 3 by severity; where 0=None, 1=Mild: No interference with daily activity, 2=Moderate: Interference with daily activity, 3=Severe: Prevents daily activity; A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it. The percentages were rounded off to the first decimal place.

    Measured: Within 14 days after each vaccination

  6. Percentage of Participants With Any Unsolicited Adverse Events (AEs) After Each Vaccination

    An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration.

    Measured: Up to 28 days (Day of Vaccination+27 Subsequent Days) after each vaccination

  7. Percentage of Participants With Serious Adverse Events (SAEs)

    A SAE is defined as any untoward medical occurrence that: 1) results in death, 2) is life-threatening, 3) requires inpatient hospitalization or prolongation of existing hospitalization, 4) results in persistent or significant disability/incapacity, 5) leads to a congenital anomaly/birth defect in the offspring of the participant or 6) is an medically important event that satisfies any of the following: a) May require intervention to prevent items 1 through 5 above. b) May expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization.

    Measured: From the first vaccination on Day 1 until the end of the trial (Day 270)

  8. Percentage of Participants With Medically Attended AEs (MAAEs)

    MAAEs are defined as AEs leading to a medical visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria.

    Measured: From the first vaccination on Day 1 until the end of the trial (Day 270)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2018
  2. Study start16 May 2018
  3. Primary completion3 Oct 2018
  4. Study completion9 Jul 2019

Resources

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
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Investigator, Outcomes assessor
Enrolment
900 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03525119
Sponsor's protocol ID
DEN-314
Other IDs
2017-001071-23, U1111-1192-7761, 18/NW/0008, 2017
Status last verified
Aug 2022
First submitted
27 Apr 2018
Last updated
19 Aug 2022
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

Publications

  • Tricou V, Eyre S, Ramjee M, Collini P, Mojares Z, Loeliger E, Mandaric S, Rauscher M, Brose M, Lefevre I, Folschweiller N, Wallace D. A randomized phase 3 trial of the immunogenicity and safety of coadministration of a live-attenuated tetravalent dengue vaccine (TAK-003) and an inactivated hepatitis a (HAV) virus vaccine in a dengue non-endemic country. Vaccine. 2023 Feb 10;41(7):1398-1407. doi: 10.1016/j.vaccine.2023.01.007. Epub 2023 Jan 19.

    PubMed 36681529

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing TDV and HAV Vaccine in people with Healthy Volunteers, run by Takeda at 10 sites in United Kingdom.

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 4 inclusion and 38 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: finished, as of the sponsor's last update on 19 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 10 sites in United Kingdom. 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. 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?

Yes. Results are posted in the registry (first posted 13 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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 of Participants HAV/Dengue Virus (DENV)-Naive at Baseline Who Are Seroprotected Against HAV at Day 30 (time frame: One month post first vaccination (Day 30)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03525119, which also lists 1 linked publication.

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 19 Aug 2022.

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