Clinical trial NCT03525119: Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) Co-administered With an Hepatitis A Virus Vaccine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Healthy Volunteers
Keywords: Vaccine
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2018-05-15
Enrollment: 900
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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 hepatitis.

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.

Eligibility criteria: Inclusion Criteria:

1. The participant is aged 18 to 60 years, inclusive.
2. 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.
3. 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.
4. Participants who can comply with trial procedures and are available for the duration of follow-up.

Exclusion Criteria:

1. Participants with an elevated oral temperature (≥38°C or 100.4°F) within 3 days of the intended date of vaccination.
2. Known hypersensitivity or allergy to any of the vaccine components (including excipients of the investigational vaccines or placebo).
3. 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.
4. Participants with any history of progressive or severe neurologic disorder, seizure disorder orneuro-inflammatory disease (eg, Guillain-Barré syndrome).
5. 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.
6. Known or suspected impairment/alteration of immune function, including:

   1. 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).
   2. 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).
   3. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial.
   4. Receipt of immunostimulants within 60 days prior to Day 1 (Month 0).
   5. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).
   6. Human immunodeficiency virus (HIV) infection or HIV-related disease.
   7. Hepatitis A virus (HAV) infection.
   8. Hepatitis C virus infection.
   9. Genetic immunodeficiency.
7. Abnormalities of splenic or thymic function.
8. Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.
9. Participants with any serious chronic or progressive disease according to judgment of the Investigator (eg, neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
10. Participants with body mass index (BMI) greater than or equal to 35 kg/m\^2 (=weight in kg/\[height in meters\^2\]).
11. 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.
12. 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.
13. Previous HAV vaccination (in a clinical trial or with an approved product).
14. Participants involved in the trial conduct or their first degree relatives.
15. Participants with history of substance or alcohol abuse within the past 2 years.
16. Female participants who are pregnant or breastfeeding.
17. 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).

    1. 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
    2. 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 (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.
18. 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.
19. Any positive or indeterminate pregnancy test.
20. Previous and planned vaccination (during the trial conduct) against any flaviviruses including dengue, yellow fever (YF), Japanese Encephalitis (JE) viruses or tick-borne encephalitis.
21. 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.
22. 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.
23. Participants with contraindications, warnings and/or precautions to vaccination with the HAV vaccine as specified within the product information.

Primary outcomes:
measure: Percentage of Participants HAV/Dengue Virus (DENV)-Naive at Baseline Who Are Seroprotected Against HAV at Day 30
timeFrame: One month post first vaccination (Day 30)
Secondary outcomes:
measure: 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
timeFrame: One month post first vaccination (Day 30) and one month post second vaccination (Day 120)
measure: Percentage of Participants HAV/DENV-naive at Baseline Who Are Seropositive for Each of the 4 Dengue Serotypes at Day 30 and Day 120
timeFrame: One month post first vaccination (Day 30) and one month post second vaccination (Day 120)
measure: Geometric Mean Concentrations (GMC) of Anti-HAV Antibodies at Day 30 in Participants HAV/DENV-naive at Baseline
timeFrame: One month post first vaccination (Day 30)
measure: Percentage of Participants With Solicited (Local Injection) Site Adverse Events (AEs) by Severity After Each Vaccination
timeFrame: Within 7 days after each vaccination
measure: Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination
timeFrame: Within 14 days after each vaccination
measure: Percentage of Participants With Any Unsolicited Adverse Events (AEs) After Each Vaccination
timeFrame: Up to 28 days (Day of Vaccination+27 Subsequent Days) after each vaccination
measure: Percentage of Participants With Serious Adverse Events (SAEs)
timeFrame: From the first vaccination on Day 1 until the end of the trial (Day 270)
measure: Percentage of Participants With Medically Attended AEs (MAAEs)
timeFrame: From the first vaccination on Day 1 until the end of the trial (Day 270)
Other outcomes:
Locations:
city: Edgbaston
country: United Kingdom
facility: Synexus - Midlands
state: Birmingham
city: Chorley
country: United Kingdom
facility: Synexus - Lancashire
state: Lancashire
city: Waterloo
country: United Kingdom
facility: Synexus - Merseyside
state: Liverpool
city: Sheffield
country: United Kingdom
facility: Royal Hallamshire Hospital
state: Yorkshire
city: Cardiff
country: United Kingdom
facility: Synexus - Wales
city: Glasgow
country: United Kingdom
facility: Synexus - Scotland
city: Hexham
country: United Kingdom
facility: North East Clinical Research Centre, Hexham General Hospital
city: Manchester
country: United Kingdom
facility: Synexus - Manchester
city: Reading
country: United Kingdom
facility: Synexus - Thames Valley
city: Stockton-on-Tees
country: United Kingdom
facility: North Tees Clinical Research Centre, Middlefield Centre, University Hospital of North Tees
Study officials:
affiliation: Takeda
name: Medical Director Clinical Science
role: STUDY_DIRECTOR
References: