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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
900
TDV SC injection
HAV Vaccine IM injection.
Placebo-matching (normal saline (0.9% NaCl) SC injection.
Synexus - Midlands
Edgbaston, Birmingham, United Kingdom
Synexus - Lancashire
Chorley, Lancashire, United Kingdom
Synexus - Merseyside
Waterloo, Liverpool, United Kingdom
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.
Time frame: One month post first vaccination (Day 30)
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.
Time frame: One month post first vaccination (Day 30) and one month post second vaccination (Day 120)
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.
Time frame: One month post first vaccination (Day 30) and one month post second vaccination (Day 120)
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.
Time frame: One month post first vaccination (Day 30)
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.
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Placebo-matching (normal saline (0.9% NaCl) IM injection.
Royal Hallamshire Hospital
Sheffield, Yorkshire, United Kingdom
Synexus - Wales
Cardiff, United Kingdom
Synexus - Scotland
Glasgow, United Kingdom
North East Clinical Research Centre, Hexham General Hospital
Hexham, United Kingdom
Synexus - Manchester
Manchester, United Kingdom
Synexus - Thames Valley
Reading, United Kingdom
North Tees Clinical Research Centre, Middlefield Centre, University Hospital of North Tees
Stockton-on-Tees, United Kingdom
Time frame: Within 7 days after each vaccination
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.
Time frame: Within 14 days after each vaccination
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.
Time frame: Up to 28 days (Day of Vaccination+27 Subsequent Days) after each vaccination
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.
Time frame: From the first vaccination on Day 1 until the end of the trial (Day 270)
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.
Time frame: From the first vaccination on Day 1 until the end of the trial (Day 270)