Immunogenicity and Safety of Tetravalent Dengue Vaccine (TDV) Co-administered With an Hepatitis A Virus Vaccine
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|ClinicalTrials.gov Identifier: NCT03525119|
Recruitment Status : Active, not recruiting
First Posted : May 15, 2018
Last Update Posted : November 21, 2018
|Condition or disease||Intervention/treatment||Phase|
|Healthy Volunteers||Biological: TDV Biological: Placebo Biological: HAV Vaccine||Phase 3|
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 placebo (SC), co-administered at Day 1 (Month 0 [M0]); placebo (SC) administered at Day 90 (Month 3 [M3])
- Group 2: TDV (SC) and placebo (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 (Clinical Trial)|
|Estimated Enrollment :||900 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Investigator, Outcomes Assessor)|
|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|
|Actual Study Start Date :||May 16, 2018|
|Estimated Primary Completion Date :||December 7, 2018|
|Estimated Study Completion Date :||June 11, 2019|
HAV Vaccine 1.0 ml + Placebo
HAV vaccine 1.0 ml, injection, IM, and placebo, injection, SC, once on Day 1 (first dose) followed by placebo, injection, SC on Day 90 (second dose).
Biological: HAV Vaccine
HAV Vaccine IM injection
Normal Saline (0.9% NaCl) SC injection
Experimental: TDV 0.5 ml + Placebo
TDV 0.5 ml, injection, SC, and placebo, injection, IM, once on Day 1 (first dose) followed by TDV 0.5 ml, injection, SC on Day 90 (second dose).
TDV SC injection
Normal Saline (0.9% NaCl) IM injection
Experimental: TDV 0.5 ml + HAV Vaccine 1.0 ml
TDV 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).
TDV SC injection
Biological: HAV Vaccine
HAV Vaccine IM injection
- Percentage of Participants HAV/Dengue Virus (DENV)-naive at Baseline who are Seroprotected Against HAV at Day 30 as Measured by Enzyme-Linked Immunosorbent Assay (ELISA) (Seroprotection Rate) (Immunogenicity Subset) [ Time Frame: One month post first vaccination (Day 30) ]Seroprotection is defined as serum anti-HAV antibody levels ≥10 mIU/ml, measured by ELISA. Immunological naivety to HAV/DENV is defined as anti-HAV antibody levels <10 mIU/ml and reciprocal neutralizing titers for all 4 dengue serotypes <10.
- 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 (Immunogenicity Subset) [ Time Frame: One month post first vaccination (Day 30) and one month post second vaccination (Day 120) ]GMTs of neutralizing antibodies will be measured by microneutralization test 50% [MNT50] for each of the 4 Dengue Serotypes.
- Percentage of Participants HAV/DENV-naive at Baseline who are Seropositive for Each of the 4 Dengue Serotypes at Day 30 and Day 120 (Immunogenicity Subset) [ Time Frame: One month post first vaccination (Day 30) and one month post second vaccination (Day 120) ]Seropositivity is defined as a reciprocal neutralizing titer ≥10.
- Geometric Mean Concentrations (GMC) of Anti-HAV Antibodies at Day 30 in Participants HAV/DENV-naive at Baseline (Immunogenicity Subset) [ Time Frame: One month post first vaccination (Day 30) ]GMC of anti-HAV antibodies will be measured by ELISA.
- Percentage of Participants with Solicited (Local Injection) Site Adverse Events (AEs) by Severity (in all Participants) [ Time Frame: Days 1 through 7 after each vaccination ]Solicited local AEs at injection site include injection site pain, injection site erythema, and injection site swelling at each injection site that occurred within 7 days after each vaccination.
- Percentage of Participants with Solicited Systemic Adverse Events (AEs) by Severity (in all Participants) [ Time Frame: Days 1 through 14 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) will be 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; Fever is defined as greater than or equal to 38°C (100.4°F) regardless of method taken.
- Percentage of Participants with any Unsolicited Adverse Events (AEs) (in all Participants) [ Time Frame: Up to 28 days (Day of Vaccination+27 Subsequent Days) 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.
- Percentage of Participants with Serious Adverse Events (SAEs) (in all Participants) [ Time Frame: First Dose (Day 1) up to 6 Months Post Second Dose (Day 270) ]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.
- Percentage of Participants with Medically Attended AEs (MAAEs) (in all Participants) [ Time Frame: First Dose (Day 1) up to 6 Months Post Second Dose (Day 270) ]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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03525119
|Synexus - Midlands|
|Edgbaston, Birmingham, United Kingdom, B15 2SQ|
|Synexus - Lancashire|
|Chorley, Lancashire, United Kingdom, PR7 7NA|
|Synexus - Merseyside|
|Waterloo, Liverpool, United Kingdom, L22 0LG|
|Royal Hallamshire Hospital|
|Sheffield, Yorkshire, United Kingdom, S10 2JF|
|Synexus - Wales|
|Cardiff, United Kingdom, CF15 9SS|
|Synexus - Scotland|
|Glasgow, United Kingdom, G20 0SP|
|North East Clinical Research Centre, Hexham General Hospital|
|Hexham, United Kingdom, NE46 1QJ|
|Synexus - Manchester|
|Manchester, United Kingdom, M15 6SX|
|Synexus - Thames Valley|
|Reading, United Kingdom, RG2 0TG|
|North Tees Clinical Research Centre, Middlefield Centre, University Hospital of North Tees|
|Stockton-on-Tees, United Kingdom, TS19 8PE|
|Study Director:||Medical Director Clinical Science||Takeda|