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

• Sponsor: Takeda (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03525119
• Collaborator: (none)
• Enrollment: 900
• Locations: 10
• Arms: 3
• Actual Duration (Months): 13.8
• Patients Per Site: 90
• Patients Per Site Per Month: 6.5

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy Volunteers	Biological: TDV; Biological: HAV Vaccine; Biological: TDV Placebo; Biological: HAV Vaccine Placebo	Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 900 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• 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
• Actual Primary Completion Date: Oct 3, 2018
• Actual Study Completion Date: Jul 9, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: HAV Vaccine 1.0 ml + Placebo/ Placebo HAV 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).	Biological: HAV Vaccine; HAV Vaccine IM injection.; Biological: TDV Placebo; Placebo-matching (normal saline (0.9% NaCl) SC injection.
Experimental: TDV 0.5 ml + Placebo/ TDV 0.5 ml TDV 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).	Biological: TDV; TDV SC injection; Biological: HAV Vaccine Placebo; Placebo-matching (normal saline (0.9% NaCl) IM injection.
Experimental: TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 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).	Biological: TDV; TDV SC injection; Biological: HAV Vaccine; HAV Vaccine IM injection.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants HAV/Dengue Virus (DENV)-Naive at Baseline Who Are Seroprotected Against HAV at Day 30 [One month post first vaccination (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.

Secondary Outcome Measures

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 [One month post first vaccination (Day 30) and one month post second vaccination (Day 120)]

   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.

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 [One month post first vaccination (Day 30) and one month post second vaccination (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.

3. Geometric Mean Concentrations (GMC) of Anti-HAV Antibodies at Day 30 in Participants HAV/DENV-naive at Baseline [One month post first vaccination (Day 30)]

   GMC of anti-HAV antibodies were measured by ELISA.

4. Percentage of Participants With Solicited (Local Injection) Site Adverse Events (AEs) by Severity After Each Vaccination [Within 7 days 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.

5. Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination [Within 14 days 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.

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

7. Percentage of Participants With Serious Adverse Events (SAEs) [From the first vaccination on Day 1 until the end of the trial (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.

8. Percentage of Participants With Medically Attended AEs (MAAEs) [From the first vaccination on Day 1 until the end of the trial (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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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:

7. 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

1. (use of inhaled, intranasal, or topical corticosteroids is allowed).

1. 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).

2. Administration of immunoglobulins and/or any blood products within the 3 months prior to Day 1 (Month 0) or planned administration during the trial.

3. Receipt of immunostimulants within 60 days prior to Day 1 (Month 0).

4. Immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within 6 months prior to Day 1 (Month 0).

5. Human immunodeficiency virus (HIV) infection or HIV-related disease.

6. Hepatitis A virus (HAV) infection.

7. Hepatitis C virus infection.

8. Genetic immunodeficiency.

9. Abnormalities of splenic or thymic function.

10. Participants with a known bleeding diathesis, or any condition that may be associated with a prolonged bleeding time.

11. Participants with any serious chronic or progressive disease according to judgment of the Investigator (eg, neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).

12. Participants with body mass index (BMI) greater than or equal to 35 kg/m^{2 (=weight in kg/[height in meters}2]).

13. 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.

14. 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.

15. Previous HAV vaccination (in a clinical trial or with an approved product).

16. Participants involved in the trial conduct or their first degree relatives.

17. Participants with history of substance or alcohol abuse within the past 2 years.

18. Female participants who are pregnant or breastfeeding.

19. 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).

20. 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

21. Acceptable birth control methods are defined as one or more of the following:

1. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring).

1. Barrier method (condom with spermicide or diaphragm with spermicide) each and every time during intercourse.

2. 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.

1. 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.

2. Any positive or indeterminate pregnancy test.

3. Previous and planned vaccination (during the trial conduct) against any flaviviruses including dengue, yellow fever (YF), Japanese Encephalitis (JE) viruses or tick-borne encephalitis.

4. 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.

5. 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.

6. Participants with contraindications, warnings and/or precautions to vaccination with the HAV vaccine as specified within the product information.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Synexus - Midlands	Edgbaston	Birmingham	United Kingdom	B15 2SQ
2	Synexus - Lancashire	Chorley	Lancashire	United Kingdom	PR7 7NA
3	Synexus - Merseyside	Waterloo	Liverpool	United Kingdom	L22 0LG
4	Royal Hallamshire Hospital	Sheffield	Yorkshire	United Kingdom	S10 2JF
5	Synexus - Wales	Cardiff		United Kingdom	CF15 9SS
6	Synexus - Scotland	Glasgow		United Kingdom	G20 0SP
7	North East Clinical Research Centre, Hexham General Hospital	Hexham		United Kingdom	NE46 1QJ
8	Synexus - Manchester	Manchester		United Kingdom	M15 6SX
9	Synexus - Thames Valley	Reading		United Kingdom	RG2 0TG
10	North Tees Clinical Research Centre, Middlefield Centre, University Hospital of North Tees	Stockton-on-Tees		United Kingdom	TS19 8PE

Sponsors and Collaborators

• Takeda

Investigators

• Study Director: Medical Director Clinical Science, Takeda

Study Documents (Full-Text)

• Study Protocol - Mar 11, 2019
• Statistical Analysis Plan - Sep 13, 2019

More Information

Additional Information:

• To obtain more information about this study, click this link.

Publications

None provided.

• Responsible Party: Takeda
• ClinicalTrials.gov Identifier: NCT03525119
• Other Study ID Numbers: DEN-314; 2017-001071-23; U1111-1192-7761; 18/NW/0008
• First Posted: May 15, 2018
• Last Update Posted: Aug 19, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Takeda: Vaccine
• Additional relevant MeSH terms: Dengue; Hepatitis A; Vaccines

Study Results

Participant Flow

Recruitment Details	Participants took part in the study at 10 investigative sites in United Kingdom from 16-May-2018 to 09-Jul-2019.
Pre-assignment Detail	Healthy participants were randomized in 1:1:1 ratio in 3 parallel groups: Group 1 received 1 dose of Hepatitis A Virus (HAV) vaccine and Tetravalent Dengue Vaccine Candidate (TDV) placebo matching injection, Group 2 received 2 doses of TDV and HAV vaccine placebo matching injection and Group 3 received 1 dose of HAV vaccine and 2 doses of TDV.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Period Title: Overall Study
STARTED	300	300	300
Safety Population	299	300	298
COMPLETED	260	261	257
NOT COMPLETED	40	39	43

Baseline Characteristics

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml	Total
Arm/Group Description	HAV 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).	TDV 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).	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).	Total of all reporting groups
Overall Participants	300	300	300	900
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34.7 (12.03)	36.0 (11.88)	35.5 (11.94)	35.4 (11.95)
Sex: Female, Male (Count of Participants)
Female	107 35.7%	120 40%	90 30%	317 35.2%
Male	193 64.3%	180 60%	210 70%	583 64.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	6 2%	4 1.3%	1 0.3%	11 1.2%
Not Hispanic or Latino	290 96.7%	293 97.7%	296 98.7%	879 97.7%
Unknown or Not Reported	4 1.3%	3 1%	3 1%	10 1.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.3%	0 0%	0 0%	1 0.1%
Asian	5 1.7%	9 3%	11 3.7%	25 2.8%
Native Hawaiian or Other Pacific Islander	1 0.3%	1 0.3%	0 0%	2 0.2%
Black or African American	6 2%	4 1.3%	6 2%	16 1.8%
White	280 93.3%	281 93.7%	279 93%	840 93.3%
More than one race	7 2.3%	4 1.3%	4 1.3%	15 1.7%
Unknown or Not Reported	0 0%	1 0.3%	0 0%	1 0.1%
Region of Enrollment (Count of Participants)
United Kingdom	300 100%	300 100%	300 100%	900 100%
Height (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	173.80 (9.299)	172.12 (9.163)	173.00 (9.110)	172.97 (9.207)
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	79.24 (15.547)	78.18 (15.570)	78.92 (15.243)	78.78 (15.444)
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.16 (4.256)	26.31 (4.354)	26.29 (4.283)	26.25 (4.293)
Baseline Seroprotection Against HAV (Count of Participants)
Yes	31 10.3%	38 12.7%	30 10%	99 11%
No	87 29%	83 27.7%	92 30.7%	262 29.1%
Baseline Seropositivity Status for Dengue (Count of Participants)
Seropositive	11 3.7%	8 2.7%	9 3%	28 3.1%
Seronegative	107 35.7%	111 37%	111 37%	329 36.6%
Baseline Seropositivity Rate for Each Dengue Serotype (Count of Participants)
DENV-1	6 2%	6 2%	5 1.7%	17 1.9%
DENV-2	4 1.3%	2 0.7%	5 1.7%	11 1.2%
DENV-3	4 1.3%	1 0.3%	1 0.3%	6 0.7%
DENV-4	1 0.3%	2 0.7%	2 0.7%	5 0.6%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

HAV PPS: All HAV & DENV-naïve participants in the immunogenicity subset who received at least 1 dose of trial vaccine, with available Day 1 and Day 30 HAV immunogenicity measurements, and who have no major protocol violations.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Measure Participants	68	66	79
Number (95% Confidence Interval) [percentage of participants]	97.1 32.4%	9.1 3%	98.7 32.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	HAV Vaccine 1.0 ml + Placebo/ Placebo, TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	As per predefined criteria in protocol the non-inferiority was established only between group 1 and group 3. Non-inferiority of HAV+TDV to HAV was established if the upper bound of the 95% CI was less than 10%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Seroprotection Rate Difference
	Estimated Value	-1.68
	Confidence Interval	(2-Sided) 95%; -8.91 to 4.28
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	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
Description	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)

Outcome Measure Data

Analysis Population Description

TDV PPS: All HAV & DENV-naïve participants in the immunogenicity subset who received at least 1 dose of trial vaccine, with available Day 1 and at least 1 post-dose immunogenicity measurements, and who have no major protocol violations. Number analyzed are participants with data available at the given timepoint.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Measure Participants	66	63	67
DENV 1, Day 30	5.0	108.2	152.5
DENV 2, Day 30	6.0	2897.9	3960.0
DENV 3, Day 30	5.3	95.4	140.5
DENV 4, Day 30	5.0	74.3	142.1
DENV 1, Day 120	5.0	171.3	173.7
DENV 2, Day 120	5.7	2064.1	1764.3
DENV 3, Day 120	5.0	83.8	92.6
DENV 4, Day 120	5.0	56.1	81.4

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

TDV PPS: All HAV & DENV-naïve participants in the immunogenicity subset who received at least 1 dose of trial vaccine, with available Day 1 and at least 1 post-dose immunogenicity measurements, and who have no major protocol violations. Number analyzed are participants with data available at the given timepoint.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Measure Participants	66	63	67
DENV 1, Day 30	0 0%	88.3 29.4%	95.4 31.8%
DENV 2, Day 30	8.2 2.7%	91.7 30.6%	96.9 32.3%
DENV 3, Day 30	1.6 0.5%	85.0 28.3%	95.4 31.8%
DENV 4, Day 30	0 0%	86.7 28.9%	90.8 30.3%
DENV 1, Day 120	0 0%	100.0 33.3%	100.0 33.3%
DENV 2, Day 120	6.0 2%	100.0 33.3%	100.0 33.3%
DENV 3, Day 120	0 0%	92.7 30.9%	98.4 32.8%
DENV 4, Day 120	0 0%	96.4 32.1%	96.8 32.3%

4. Secondary Outcome

Title	Geometric Mean Concentrations (GMC) of Anti-HAV Antibodies at Day 30 in Participants HAV/DENV-naive at Baseline
Description	GMC of anti-HAV antibodies were measured by ELISA.
Time Frame	One month post first vaccination (Day 30)

Outcome Measure Data

Analysis Population Description

HAV PPS: All HAV & DENV-naïve participants in the immunogenicity subset who received at least 1 dose of trial vaccine, with available Day 1 and Day 30 HAV immunogenicity measurements, and who have no major protocol violations.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Measure Participants	68	66	79
Geometric Mean (95% Confidence Interval) [mIU/mL]	82.1	6.7	93.0

5. Secondary Outcome

Title	Percentage of Participants With Solicited (Local Injection) Site Adverse Events (AEs) by Severity After Each Vaccination
Description	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.
Time Frame	Within 7 days after each vaccination

Outcome Measure Data

Analysis Population Description

Safety Set included all participants who received at least 1 dose of trial vaccine. Number analyzed is the number of participants with data available for the specific category. Only categories for which there was at least 1 participant are reported.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Measure Participants	299	300	298
After First Vaccination IM,Any Local AEs	45.0 15%	15.4 5.1%	49.1 16.4%
After First Vaccination, IM, Pain-Any	44.6 14.9%	14.4 4.8%	48.4 16.1%
After First Vaccination, IM, Pain-Mild	38.1 12.7%	13.0 4.3%	43.9 14.6%
After First Vaccination, IM, Pain-Moderate	6.6 2.2%	1.0 0.3%	4.2 1.4%
After First Vaccination, IM, Pain-Severe	0 0%	0.3 0.1%	0.4 0.1%
After First Vaccination, IM, Erythema-Any	2.4 0.8%	2.1 0.7%	1.4 0.5%
After First Vaccination, IM, Erythema-Mild	1.7 0.6%	1.4 0.5%	1.1 0.4%
After First Vaccination, IM, Erythema-Moderate	0 0%	0.3 0.1%	0 0%
After First Vaccination, IM, Swelling-Any	1.8 0.6%	0.3 0.1%	1.1 0.4%
After First Vaccination, IM, Swelling-Mild	1.4 0.5%	0 0%	0.7 0.2%
After First Vaccination, SC,Any Local AEs	15.6 5.2%	47.3 15.8%	47.0 15.7%
After First Vaccination SC, Pain-Any	14.2 4.7%	40.4 13.5%	42.5 14.2%
After First Vaccination SC, Pain-Mild	12.5 4.2%	35.6 11.9%	36.1 12%
After First Vaccination, SC, Pain-Moderate	1.7 0.6%	4.8 1.6%	6.3 2.1%
After First Vaccination, SC, Erythema-Any	1.7 0.6%	16.8 5.6%	14.4 4.8%
After First Vaccination, SC, Erythema-Mild	1.0 0.3%	15.8 5.3%	12.3 4.1%
After First Vaccination, SC, Erythema-Moderate	0 0%	1.0 0.3%	1.8 0.6%
After First Vaccination, SC, Swelling-Any	1.0 0.3%	2.7 0.9%	2.8 0.9%
After First Vaccination, SC, Swelling-Mild	0.7 0.2%	2.7 0.9%	2.5 0.8%
After Second Vaccination, SC,Any Local AEs	11.0 3.7%	37.9 12.6%	41.0 13.7%
After Second Vaccination, SC,Pain-Any	10.6 3.5%	34.7 11.6%	37.8 12.6%
After Second Vaccination, SC,Pain-Mild	10.2 3.4%	30.9 10.3%	33.9 11.3%
After Second Vaccination, SC,Pain-Moderate	0.4 0.1%	2.7 0.9%	3.2 1.1%
After Second Vaccination, SC,Pain-Severe	0 0%	1.1 0.4%	0.8 0.3%
After Second Vaccination, SC,Erythema-Any	0.4 0.1%	12.9 4.3%	11.6 3.9%
After Second Vaccination, SC,Erythema-Mild	0.4 0.1%	12.2 4.1%	10.0 3.3%
After Second Vaccination, SC,Erythema-Moderate	0 0%	0.8 0.3%	1.2 0.4%
After Second Vaccination, SC,Swelling-Any	0.8 0.3%	4.6 1.5%	4.8 1.6%
After Second Vaccination, SC,Swelling-Mild	0.8 0.3%	3.4 1.1%	4.4 1.5%
After Second Vaccination, SC,Swelling-Moderate	0 0%	0.8 0.3%	0 0%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Safety Set included all participants who received at least 1 dose of trial vaccine. Number analyzed is the number of participants with data available for the specific category. Only categories for which there was at least 1 participant are reported.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Measure Participants	299	300	298
After First Vaccination, Any Systemic AEs	47.4 15.8%	44.2 14.7%	49.5 16.5%
After First Vaccination, Headache-Any	28.7 9.6%	32.5 10.8%	31.2 10.4%
After First Vaccination, Headache-Mild	19.0 6.3%	22.3 7.4%	20.7 6.9%
After First Vaccination, Headache-Moderate	8.7 2.9%	8.2 2.7%	8.8 2.9%
After First Vaccination, Headache-Severe	1.0 0.3%	2.1 0.7%	1.8 0.6%
After First Vaccination, Asthenia-Any	17.0 5.7%	15.8 5.3%	20.7 6.9%
After First Vaccination, Asthenia-Mild	12.8 4.3%	9.2 3.1%	16.1 5.4%
After First Vaccination, Asthenia-Moderate	4.2 1.4%	5.5 1.8%	4.2 1.4%
After First Vaccination, Asthenia-Severe	0 0%	1.0 0.3%	0.4 0.1%
After First Vaccination, Malaise-Any	17.6 5.9%	21.2 7.1%	21.8 7.3%
After First Vaccination, Malaise-Mild	11.4 3.8%	13.7 4.6%	14.0 4.7%
After First Vaccination, Malaise-Moderate	5.2 1.7%	5.8 1.9%	7.0 2.3%
After First Vaccination, Malaise-Severe	1.0 0.3%	1.7 0.6%	0.7 0.2%
After First Vaccination, Myalgia-Any	29.4 9.8%	22.9 7.6%	33.7 11.2%
After First Vaccination, Myalgia-Mild	23.9 8%	16.4 5.5%	27.7 9.2%
After First Vaccination, Myalgia-Moderate	5.2 1.7%	6.2 2.1%	5.6 1.9%
After First Vaccination, Myalgia-Severe	0.3 0.1%	0.3 0.1%	0.4 0.1%
After First Vaccination, Fever-Any	1.7 0.6%	2.7 0.9%	1.8 0.6%
After First Vaccination, Fever-38.0-<38.5	1.4 0.5%	2.1 0.7%	0.7 0.2%
After First Vaccination, Fever-38.5-<39.0	0.3 0.1%	0.7 0.2%	0.4 0.1%
After First Vaccination, Fever-39.0-<39.5	0 0%	0 0%	0.4 0.1%
After First Vaccination, Fever-≥41.0	0 0%	0 0%	0.4 0.1%
After Second Vaccination, Any Systemic AEs	27.6 9.2%	30.2 10.1%	33.1 11%
After Second Vaccination, Headache-Any	17.7 5.9%	17.2 5.7%	22.3 7.4%
After Second Vaccination, Headache-Mild	13.0 4.3%	12.6 4.2%	14.7 4.9%
After Second Vaccination, Headache-Moderate	4.3 1.4%	3.4 1.1%	6.0 2%
After Second Vaccination, Headache-Severe	0.4 0.1%	1.1 0.4%	1.6 0.5%
After Second Vaccination, Asthenia-Any	9.8 3.3%	7.6 2.5%	11.2 3.7%
After Second Vaccination, Asthenia-Mild	7.5 2.5%	5.0 1.7%	7.6 2.5%
After Second Vaccination, Asthenia-Moderate	2.4 0.8%	2.7 0.9%	1.6 0.5%
After Second Vaccination, Asthenia-Severe	0 0%	0 0%	2.0 0.7%
After Second Vaccination, Malaise-Any	14.6 4.9%	14.9 5%	16.3 5.4%
After Second Vaccination, Malaise-Mild	10.2 3.4%	9.9 3.3%	10.4 3.5%
After Second Vaccination, Malaise-Moderate	3.1 1%	3.8 1.3%	3.6 1.2%
After Second Vaccination, Malaise-Severe	1.2 0.4%	1.1 0.4%	2.4 0.8%
After Second Vaccination, Myalgia-Any	12.6 4.2%	15.6 5.2%	19.5 6.5%
After Second Vaccination, Myalgia-Mild	10.2 3.4%	13.0 4.3%	15.9 5.3%
After Second Vaccination, Myalgia-Moderate	2.0 0.7%	1.9 0.6%	3.2 1.1%
After Second Vaccination, Myalgia-Severe	0.4 0.1%	0.8 0.3%	0.4 0.1%
After Second Vaccination, Fever-Any	3.6 1.2%	1.1 0.4%	0.8 0.3%
After Second Vaccination, Fever-38.0-<38.5	3.2 1.1%	0.4 0.1%	0.8 0.3%
After Second Vaccination, Fever-38.5-<39.0	0 0%	0.4 0.1%	0 0%
After Second Vaccination, Fever-39.5-<40.0	0.4 0.1%	0.4 0.1%	0 0%

7. Secondary Outcome

Title	Percentage of Participants With Any Unsolicited Adverse Events (AEs) After Each Vaccination
Description	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

Outcome Measure Data

Analysis Population Description

Safety Set included all participants who received at least 1 dose of trial vaccine. Number analyzed is the number of participants with data available for the specific category.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Measure Participants	299	300	298
After First Vaccination	14.7 4.9%	17.0 5.7%	18.8 6.3%
After Second Vaccination	14.4 4.8%	10.0 3.3%	11.7 3.9%

8. Secondary Outcome

Title	Percentage of Participants With Serious Adverse Events (SAEs)
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Set included all participants who received at least 1 dose of trial vaccine.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Measure Participants	299	300	298
Number [percentage of participants]	0.7 0.2%	2.7 0.9%	2.3 0.8%

9. Secondary Outcome

Title	Percentage of Participants With Medically Attended AEs (MAAEs)
Description	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)

Outcome Measure Data

Analysis Population Description

Safety Set included all participants who received at least 1 dose of trial vaccine.

Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo	TDV 0.5 ml + Placebo/ TDV 0.5 ml	TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).	TDV 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).	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).
Measure Participants	299	300	298
Number [percentage of participants]	23.1 7.7%	21.0 7%	20.1 6.7%

Adverse Events

Time Frame	All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination.
Adverse Event Reporting Description	Safety Set included all participants who received at least 1 dose of trial vaccine.
Arm/Group Title	HAV Vaccine 1.0 ml + Placebo/ Placebo		TDV 0.5 ml + Placebo/ TDV 0.5 ml		TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
Arm/Group Description	HAV 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).		TDV 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).		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).
All Cause Mortality
	HAV Vaccine 1.0 ml + Placebo/ Placebo		TDV 0.5 ml + Placebo/ TDV 0.5 ml		TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/299 (0%)		0/300 (0%)		0/298 (0%)
Serious Adverse Events
	HAV Vaccine 1.0 ml + Placebo/ Placebo		TDV 0.5 ml + Placebo/ TDV 0.5 ml		TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/299 (0.7%)		8/300 (2.7%)		7/298 (2.3%)
Cardiac disorders
Supraventricular tachycardia	0/299 (0%)		0/300 (0%)		1/298 (0.3%)
Gastrointestinal disorders
Abdominal pain	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Abdominal strangulated hernia	1/299 (0.3%)		0/300 (0%)		0/298 (0%)
Crohn's disease	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Intestinal ischaemia	0/299 (0%)		0/300 (0%)		1/298 (0.3%)
Mesenteric vein thrombosis	0/299 (0%)		0/300 (0%)		1/298 (0.3%)
Oesophagitis	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Infections and infestations
Appendicitis	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Wound infection	1/299 (0.3%)		0/300 (0%)		0/298 (0%)
Injury, poisoning and procedural complications
Abdominal injury	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Cervical vertebral fracture	0/299 (0%)		0/300 (0%)		1/298 (0.3%)
Fractured coccyx	1/299 (0.3%)		0/300 (0%)		0/298 (0%)
Intentional overdose	0/299 (0%)		0/300 (0%)		1/298 (0.3%)
Joint dislocation	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Lower limb fracture	0/299 (0%)		0/300 (0%)		1/298 (0.3%)
Thermal burn	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer stage II	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Invasive ductal breast carcinoma	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Prostate cancer	0/299 (0%)		0/300 (0%)		1/298 (0.3%)
Nervous system disorders
Loss of consciousness	0/299 (0%)		1/300 (0.3%)		0/298 (0%)
Psychiatric disorders
Intentional self-injury	0/299 (0%)		0/300 (0%)		1/298 (0.3%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	0/299 (0%)		0/300 (0%)		1/298 (0.3%)
Other (Not Including Serious) Adverse Events
	HAV Vaccine 1.0 ml + Placebo/ Placebo		TDV 0.5 ml + Placebo/ TDV 0.5 ml		TDV 0.5 ml + HAV Vaccine 1.0 ml/ TDV 0.5 ml
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/299 (3%)		8/300 (2.7%)		11/298 (3.7%)
Infections and infestations
Nasopharyngitis	9/299 (3%)		8/300 (2.7%)		11/298 (3.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.