Study of ChimeriVax™ Tetravalent Dengue Vaccine in Healthy Subjects

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00875524
• Collaborator: (none)
• Enrollment: 180
• Location: 1
• Arms: 2
• Actual Duration (Months): 69
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

This trial evaluated the use of a tetravalent vaccine against dengue.

Primary objectives:

• To describe the humoral immune response to dengue before and after each vaccination with tetravalent dengue vaccine in adults, adolescents, and children.

• To evaluate the safety of each vaccination with tetravalent dengue vaccine in the 4 age cohorts.

• To evaluate the persistence of antibodies against dengue during 5 years after the first vaccination with tetravalent dengue vaccine in the 4 age cohorts.

Condition or Disease	Intervention/Treatment	Phase
Dengue Virus; Dengue Fever; Dengue Hemorrhagic Fever; Dengue Disease	Biological: CYD dengue vaccine serotypes (1, 2, 3, 4).; Biological: Meningococcal Polysaccharide A+C; NaCl; Typhoid Vi polysaccharide	Phase 2

Detailed Description

Safety assessments included solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 180 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: The first and second vaccinations were administered in a blind-observer manner. The third vaccination was planned to be administered in a single-blind manner; however, due to the cancellation of the statistical analysis after the second vaccination, the third vaccination was also administered in a blind- observer manner. To ensure the blind-observer design of the 3 vaccinations, the product was prepared in a separate room whether neither the Investigator nor participant had access.
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of ChimeriVax™ Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Viet Nam
• Actual Study Start Date: Mar 1, 2009
• Actual Primary Completion Date: Aug 1, 2014
• Actual Study Completion Date: Dec 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CYD Dengue Vaccine Group Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.	Biological: CYD dengue vaccine serotypes (1, 2, 3, 4).; 0.5 mL, Subcutaneous; Other Names: ChimeriVax™
Sham Comparator: Control Vaccine Group Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.	Biological: Meningococcal Polysaccharide A+C; NaCl; Typhoid Vi polysaccharide; Each at 0.5 mL, Subcutaneous, respectively; Other Names: Meningococcal Polysaccharide Vaccine A+C NaCl Typhim Vi®

Outcome Measures

Primary Outcome Measures

1. Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype of the Parental Dengue Virus Strain Before and Following Injection (Inj.) With CYD Dengue Tetravalent Vaccine [Pre-Inj. 1, 2, and 3 and 28 days Post-Inj. 1, 2, and 3]

   Geometric mean titers against each serotype of the parental dengue virus strains were assessed using the dengue Plaque Reduction Neutralization Test (PRNT).

2. Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype of the Parental Dengue Virus Strain During the Follow-up Period [Year 1, Year 2, Year 3 and Year 4 after the Third Injection]

   GMT against each serotype of the parental dengue virus strains were assessed using the dengue PRNT.

3. Percentage of Participants With Antibody Titers >= 10 (1/Dil) Against Each Serotypes of the Parental Dengue Virus Strains Following Inj. With CYD Dengue Tetravalent Vaccine [Pre-Inj. 1, 2, and 3 and 28 days Post-Inj. 1, 2, and 3]

   Antibody titer levels against each serotype of the parental dengue virus strains were assessed using the PRNT.

4. Percentage of Participants With Antibody Titers >= 10 (1/Dil) Against Each Serotypes of the Parental Dengue Virus Strains Following Inj. With CYD Dengue Tetravalent Vaccine During the Follow-up Period [Year 1, Year 2, Year 3 and Year 4 after the Third Injection]

   Antibody titer levels against each serotype of the parental dengue virus strains were assessed using the PRNT.

5. Percentage of Participants With Solicited Inj. Site Reactions Following Any and Each Inj. With CYD Dengue Tetravalent Vaccine [7 days post-each injection]

   Solicited Inj. site reactions: Pain, Erythema, and Swelling. Pain:- Grade 1: easily tolerated, Grade 2: sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities. Erythema and Swelling:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >= 5 cm.

6. Percentage of Participants With Solicited Systemic Reactions Following Any and Each Inj. With CYD Dengue Tetravalent Vaccine [14 days post-each injection]

   Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever:- Grade 1: >=37.5 degree Celsius (°C) to <=38.0°C, Grade 2: >38.0°C to <=39.0°C, Grade 3: >39.0°C. Headache, malaise, myalgia and asthenia: Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 2 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria :

• Aged 2 to 45 years on the day of inclusion.

• Provision of Informed Consent/Assent Form signed by the participant (and/or by the parent or another legally acceptable representative for participants <18 years).

• Participant (and parent/guardian for participants <18 years) able to attend all scheduled visits and to comply with all trial procedures.

• For a female participant of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to the first vaccination, until at least 4 weeks after the last vaccination.

• Participant in good health, based on medical history, physical examination and laboratory parameters.

Exclusion Criteria :

• Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia.

• For a female participant of child-bearing potential, known pregnancy or positive serum pregnancy test at Screening.

• For a female participant of child-bearing potential, known pregnancy or positive urine pregnancy test on the day of the first injection.

• Breast-feeding female participant.

• Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.

• Human immunodeficiency virus, hepatitis B, or hepatitis C seropositivity in the blood sample taken at screening.

• Planned participation in another clinical trial during the first year of the study.

• Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the past 6 months, or long-term systemic corticosteroids therapy.

• Known systemic hypersensitivity to any of the vaccine components or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.

• Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.

• Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures.

• Receipt of blood or blood-derived products in the past 3 months that might interfere with the assessment of immune response.

• Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.

• Laboratory abnormalities of at least moderate severity or clinically significant according to the Investigator in blood sample taken at screening.

• Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.

• Planned receipt of any vaccine in the 4 weeks following the first trial vaccination.

• Familial atopy medical history (parents, brothers, or sisters).

• Previous vaccination with meningococcal A+C or typhoid vaccines within 3 years prior to inclusion.

• History of meningococcal or typhoid infections (confirmed either clinically, serologically or microbiologically).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Sanofi Pasteur Investigational Site	Long Xuyên	An Giang Province	Vietnam

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Monitor, Sanofi Pasteur Inc

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT00875524
• Other Study ID Numbers: CYD22; 2014-001709-41
• First Posted: Apr 3, 2009
• Last Update Posted: Apr 5, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Sanofi Pasteur, a Sanofi Company: Dengue virus; Dengue fever; Dengue hemorrhagic fever; Dengue diseases; Dengue vaccine
• Additional relevant MeSH terms: Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Fever; Hyperthermia; Vaccines

Study Results

Participant Flow

Recruitment Details	Study participants were enrolled from 18 March 2009 to 01 July 2010 at 1 clinical center in Vietnam.
Pre-assignment Detail	A total of 180 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized.

Arm/Group Title	CYD Dengue Vaccine Group	Control Vaccine Group
Arm/Group Description	Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injection. Participants were followed for 4 years after the third injection.	Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.
Period Title: Overall Study
STARTED	120	60
Received Vaccination 1	120	60
Received Vaccination 2	116	58
Received Vaccination 3	114	58
COMPLETED	112	54
NOT COMPLETED	8	6

Baseline Characteristics

Arm/Group Title	CYD Dengue Vaccine Group	Control Group	Total
Arm/Group Description	Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.	Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.	Total of all reporting groups
Overall Participants	120	60	180
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	10.9 (8.6)	11.8 (9.6)	11.2 (8.9)
Sex: Female, Male (Count of Participants)
Female	62 51.7%	25 41.7%	87 48.3%
Male	58 48.3%	35 58.3%	93 51.7%

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype of the Parental Dengue Virus Strain Before and Following Injection (Inj.) With CYD Dengue Tetravalent Vaccine
Description	Geometric mean titers against each serotype of the parental dengue virus strains were assessed using the dengue Plaque Reduction Neutralization Test (PRNT).
Time Frame	Pre-Inj. 1, 2, and 3 and 28 days Post-Inj. 1, 2, and 3

Outcome Measure Data

Analysis Population Description

Analysis was performed on Per-protocol analysis (PPA) set which included participants who received at least 1 dose of the study vaccine and had no protocol deviations, randomization error, blood sample not taken within the period and forbidden treatments. Here, 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Vaccine Group
Arm/Group Description	Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.	Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.
Measure Participants	119	60
Dengue Parental Serotype 1; Pre-Inj. 1	32.7	19.6
Dengue Parental Serotype 1; Post-Inj. 1	70.9	18.8
Dengue Parental Serotype 1; Pre-Inj. 2	52.2	19.8
Dengue Parental Serotype 1; Post-Inj. 2	100	20.6
Dengue Parental Serotype 1; Pre-Inj. 3	70.9	24.6
Dengue Parental Serotype 1; Post-Inj. 3	129	25.3
Dengue Parental Serotype 2; Pre-Inj. 1	33.1	27.2
Dengue Parental Serotype 2; Post-Inj. 1	92.3	25.0
Dengue Parental Serotype 2; Pre-Inj. 2	74.8	29.5
Dengue Parental Serotype 2; Post-Inj. 2	195	29.3
Dengue Parental Serotype 2; Pre-Inj. 3	111	32.3
Dengue Parental Serotype 2; Post-Inj. 3	216	30.4
Dengue Parental Serotype 3; Pre-Inj. 1	31.9	20.5
Dengue Parental Serotype 3; Post-Inj. 1	95.6	18.4
Dengue Parental Serotype 3; Pre-Inj. 2	60.4	19.1
Dengue Parental Serotype 3; Post-Inj. 2	152	21.9
Dengue Parental Serotype 3; Pre-Inj. 3	87.2	26.8
Dengue Parental Serotype 3; Post-Inj. 3	169	25.2
Dengue Parental Serotype 4; Pre-Inj. 1	17.0	13.9
Dengue Parental Serotype 4; Post-Inj. 1	104	15.4
Dengue Parental Serotype 4; Pre-Inj. 2	51.7	14.1
Dengue Parental Serotype 4; Post-Inj. 2	120	14.3
Dengue Parental Serotype 4; Pre-Inj. 3	70.1	17.1
Dengue Parental Serotype 4; Post-Inj. 3	146	17.4

2. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Antibodies Against Each Serotype of the Parental Dengue Virus Strain During the Follow-up Period
Description	GMT against each serotype of the parental dengue virus strains were assessed using the dengue PRNT.
Time Frame	Year 1, Year 2, Year 3 and Year 4 after the Third Injection

Outcome Measure Data

Analysis Population Description

Analysis was performed on Full analysis set which included all the participants present at first vaccination (V01) and received at least one dose of vaccine. Here, 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Vaccine Group
Arm/Group Description	Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.	Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.
Measure Participants	120	60
Dengue Parental Serotype 1: Year 1	103	28.4
Dengue Parental Serotype 1: Year 2	72.9	25.7
Dengue Parental Serotype 1: Year 3	56.0	29.7
Dengue Parental Serotype 1: Year 4	52.6	30.5
Dengue Parental Serotype 2: Year 1	133	36.9
Dengue Parental Serotype 2: Year 2	118	42.6
Dengue Parental Serotype 2: Year 3	78.1	45.2
Dengue Parental Serotype 2: Year 4	73.7	50.7
Dengue Parental Serotype 3: Year 1	145	31.8
Dengue Parental Serotype 3: Year 2	88.2	26.1
Dengue Parental Serotype 3: Year 3	66.6	24.4
Dengue Parental Serotype 3: Year 4	42.7	19.7
Dengue Parental Serotype 4: Year 1	87.5	19.0
Dengue Parental Serotype 4: Year 2	56.9	17.5
Dengue Parental Serotype 4: Year 3	47.3	21.7
Dengue Parental Serotype 4: Year 4	30.2	18.2

3. Primary Outcome

Title	Percentage of Participants With Antibody Titers >= 10 (1/Dil) Against Each Serotypes of the Parental Dengue Virus Strains Following Inj. With CYD Dengue Tetravalent Vaccine
Description	Antibody titer levels against each serotype of the parental dengue virus strains were assessed using the PRNT.
Time Frame	Pre-Inj. 1, 2, and 3 and 28 days Post-Inj. 1, 2, and 3

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPA set. Here, 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Vaccine Group
Arm/Group Description	Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.	Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.
Measure Participants	119	60
Dengue Parental Serotype 1; Pre-Inj. 1	50.4 42%	43.3 72.2%
Dengue Parental Serotype 1; Post-Inj. 1	62.2 51.8%	41.7 69.5%
Dengue Parental Serotype 1; Pre-Inj. 2	58.3 48.6%	39.7 66.2%
Dengue Parental Serotype 1; Post-Inj. 2	79.1 65.9%	41.4 69%
Dengue Parental Serotype 1; Pre-Inj. 3	68.4 57%	46.6 77.7%
Dengue Parental Serotype 1; Post-Inj. 3	93.0 77.5%	41.4 69%
Dengue Parental Serotype 2; Pre-Inj. 1	49.6 41.3%	41.7 69.5%
Dengue Parental Serotype 2; Post-Inj. 1	66.4 55.3%	35.6 59.3%
Dengue Parental Serotype 2; Pre-Inj. 2	63.5 52.9%	39.7 66.2%
Dengue Parental Serotype 2; Post-Inj. 2	93.9 78.3%	41.4 69%
Dengue Parental Serotype 2; Pre-Inj. 3	80.7 67.3%	43.1 71.8%
Dengue Parental Serotype 2; Post-Inj. 3	99.1 82.6%	43.1 71.8%
Dengue Parental Serotype 3; Pre-Inj. 1	63.0 52.5%	52.5 87.5%
Dengue Parental Serotype 3; Post-Inj. 1	84.9 70.8%	47.5 79.2%
Dengue Parental Serotype 3; Pre-Inj. 2	73.0 60.8%	46.6 77.7%
Dengue Parental Serotype 3; Post-Inj. 2	94.8 79%	53.4 89%
Dengue Parental Serotype 3; Pre-Inj. 3	85.1 70.9%	62.1 103.5%
Dengue Parental Serotype 3; Post-Inj. 3	99.1 82.6%	58.6 97.7%
Dengue Parental Serotype 4; Pre-Inj. 1	44.5 37.1%	37.3 62.2%
Dengue Parental Serotype 4; Post-Inj. 1	77.3 64.4%	41.7 69.5%
Dengue Parental Serotype 4; Pre-Inj. 2	73.0 60.8%	39.7 66.2%
Dengue Parental Serotype 4; Post-Inj. 2	89.6 74.7%	40.4 67.3%
Dengue Parental Serotype 4; Pre-Inj. 3	84.2 70.2%	43.1 71.8%
Dengue Parental Serotype 4; Post-Inj. 3	95.6 79.7%	43.1 71.8%

4. Primary Outcome

Title	Percentage of Participants With Antibody Titers >= 10 (1/Dil) Against Each Serotypes of the Parental Dengue Virus Strains Following Inj. With CYD Dengue Tetravalent Vaccine During the Follow-up Period
Description	Antibody titer levels against each serotype of the parental dengue virus strains were assessed using the PRNT.
Time Frame	Year 1, Year 2, Year 3 and Year 4 after the Third Injection

Outcome Measure Data

Analysis Population Description

Analysis was performed on Full analysis set. Here, 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Vaccine Group
Arm/Group Description	Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.	Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.
Measure Participants	120	60
Dengue Parental Serotype 1: Year 1	78.8 65.7%	43.9 73.2%
Dengue Parental Serotype 1: Year 2	74.1 61.8%	38.6 64.3%
Dengue Parental Serotype 1: Year 3	59.8 49.8%	40.0 66.7%
Dengue Parental Serotype 1: Year 4	61.6 51.3%	40.7 67.8%
Dengue Parental Serotype 2: Year 1	86.7 72.3%	47.4 79%
Dengue Parental Serotype 2: Year 2	82.1 68.4%	49.1 81.8%
Dengue Parental Serotype 2: Year 3	70.5 58.8%	50.9 84.8%
Dengue Parental Serotype 2: Year 4	68.8 57.3%	53.7 89.5%
Dengue Parental Serotype 3: Year 1	92.9 77.4%	54.4 90.7%
Dengue Parental Serotype 3: Year 2	86.6 72.2%	54.4 90.7%
Dengue Parental Serotype 3: Year 3	75.0 62.5%	54.5 90.8%
Dengue Parental Serotype 3: Year 4	70.5 58.8%	44.4 74%
Dengue Parental Serotype 4: Year 1	88.5 73.8%	47.4 79%
Dengue Parental Serotype 4: Year 2	90.2 75.2%	40.4 67.3%
Dengue Parental Serotype 4: Year 3	87.5 72.9%	47.3 78.8%
Dengue Parental Serotype 4: Year 4	76.8 64%	42.6 71%

5. Primary Outcome

Title	Percentage of Participants With Solicited Inj. Site Reactions Following Any and Each Inj. With CYD Dengue Tetravalent Vaccine
Description	Solicited Inj. site reactions: Pain, Erythema, and Swelling. Pain:- Grade 1: easily tolerated, Grade 2: sufficiently discomforting to interfere with normal behavior or activities, Grade 3: Incapacitating, unable to perform usual activities. Erythema and Swelling:- Grade 1: <2.5 cm, Grade 2: >=2.5 to <5 cm, Grade 3: >= 5 cm.
Time Frame	7 days post-each injection

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety analysis set. Here, 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Vaccine Group
Arm/Group Description	Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.	Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.
Measure Participants	120	60
Inj. site Pain; Post-Any Inj.	28.3 23.6%	80 133.3%
Grade 3 Inj. site Pain; Post-Any Inj.	0.0 0%	0.0 0%
Inj. site Erythema; Post-Any Inj.	6.7 5.6%	21.7 36.2%
Grade 3 Inj. site Erythema; Post-Any Inj.	0.0 0%	1.7 2.8%
Inj. site Swelling; Post-Any Inj.	4.2 3.5%	15.0 25%
Grade 3 Inj. site Swelling; Post-Any Inj.	0.0 0%	1.7 2.8%
Inj. site Pain; Post-Inj. 1	15.8 13.2%	73.3 122.2%
Grade 3 Inj. site Pain; Post-Inj. 1	0.0 0%	0.0 0%
Inj. site Erythema; Post-Inj. 1	4.2 3.5%	16.7 27.8%
Grade 3 Inj. site Erythema; Post-Inj. 1	0.0 0%	1.7 2.8%
Inj. site Swelling; Post-Inj. 1	1.7 1.4%	6.7 11.2%
Grade 3 Inj. site Swelling; Post-Inj. 1	0.0 0%	1.7 2.8%
Inj. site Pain; Post-Inj. 2	15.5 12.9%	15.5 25.8%
Grade 3 Inj. site Pain; Post-Inj. 2	0.0 0%	0.0 0%
Inj. site Erythema; Post-Inj. 2	4.3 3.6%	5.2 8.7%
Grade 3 Inj. site Erythema; Post-Inj. 2	0.0 0%	0.0 0%
Inj. site Swelling; Post-Inj. 2	2.6 2.2%	3.4 5.7%
Grade 3 Inj. site Swelling; Post-Inj. 2	0.0 0%	0.0 0%
Inj. site Pain; Post-Inj. 3	11.4 9.5%	41.4 69%
Grade 3 Inj. site Pain; Post-Inj. 3	0.0 0%	0.0 0%
Inj. site Erythema; Post-Inj. 3	2.6 2.2%	5.2 8.7%
Grade 3 Inj. site Erythema; Post-Inj. 3	0.0 0%	0.0 0%
Inj. site Swelling; Post-Inj. 3	0.0 0%	6.9 11.5%
Grade 3 Inj. site Swelling; Post-Inj. 3	0.0 0%	0.0 0%

6. Primary Outcome

Title	Percentage of Participants With Solicited Systemic Reactions Following Any and Each Inj. With CYD Dengue Tetravalent Vaccine
Description	Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever:- Grade 1: >=37.5 degree Celsius (°C) to <=38.0°C, Grade 2: >38.0°C to <=39.0°C, Grade 3: >39.0°C. Headache, malaise, myalgia and asthenia: Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities.
Time Frame	14 days post-each injection

Outcome Measure Data

Analysis Population Description

Analysis was performed on Safety analysis set. Here, 'number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Vaccine Group
Arm/Group Description	Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.	Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.
Measure Participants	120	60
Fever; Post-Any Inj.	27.5 22.9%	26.7 44.5%
Grade 3 Fever; Post-Any Inj.	0.8 0.7%	3.3 5.5%
Headache; Post-Any Inj.	35.3 29.4%	30.0 50%
Grade 3 Headache; Post-Any Inj.	0.8 0.7%	0.0 0%
Malaise; Post-Any Inj.	29.4 24.5%	23.3 38.8%
Grade 3 Malaise; Post-Any Inj.	0.0 0%	0.0 0%
Myalgia; Post-Any Inj.	20.2 16.8%	23.3 38.8%
Grade 3 Myalgia; Post-Any Inj.	0.0 0%	0.0 0%
Asthenia; Post-Any Inj.	13.4 11.2%	5.0 8.3%
Grade 3 Asthenia; Post-Any Inj.	1.7 1.4%	0.0 0%
Fever; Post-Inj. 1	19.2 16%	15.0 25%
Grade 3 Fever; Post-Inj. 1	0.8 0.7%	3.3 5.5%
Headache; Post-Inj. 1	29.4 24.5%	28.3 47.2%
Grade 3 Headache; Post-Inj. 1	0.8 0.7%	0.0 0%
Malaise; Post-Inj. 1	21.8 18.2%	16.7 27.8%
Grade 3 Malaise; Post-Inj. 1	0.0 0%	0.0 0%
Myalgia; Post-Inj. 1	15.1 12.6%	20.0 33.3%
Grade 3 Myalgia; Post-Inj. 1	0.0 0%	0.0 0%
Asthenia; Post-Inj. 1	8.4 7%	0.0 0%
Grade 3 Asthenia; Post-Inj. 1	0.8 0.7%	0.0 0%
Fever; Post-Inj. 2	12.1 10.1%	6.9 11.5%
Grade 3 Fever; Post-Inj. 2	0.0 0%	0.0 0%
Headache; Post-Inj. 2	15.7 13.1%	8.6 14.3%
Grade 3 Headache; Post-Inj. 2	0.0 0%	0.0 0%
Malaise; Post-Inj. 2	13.0 10.8%	8.6 14.3%
Grade 3 Malaise; Post-Inj. 2	0.0 0%	0.0 0%
Myalgia; Post-Inj. 2	9.6 8%	5.2 8.7%
Grade 3 Myalgia; Post-Inj. 2	0.0 0%	0.0 0%
Asthenia; Post-Inj. 2	6.1 5.1%	1.7 2.8%
Grade 3 Asthenia; Post-Inj. 2	0.9 0.8%	0.0 0%
Fever; Post-Inj. 3	3.5 2.9%	8.6 14.3%
Grade 3 Fever; Post-Inj. 3	0.0 0%	0.0 0%
Headache; Post-Inj. 3	8.8 7.3%	10.3 17.2%
Grade 3 Headache; Post-Inj. 3	0.0 0%	0.0 0%
Malaise; Post-Inj. 3	5.3 4.4%	8.6 14.3%
Grade 3 Malaise; Post-Inj. 3	0.0 0%	0.0 0%
Myalgia; Post-Inj. 3	4.4 3.7%	10.3 17.2%
Grade 3 Myalgia; Post-Inj. 3	0.0 0%	0.0 0%
Asthenia; Post-Inj. 3	0.9 0.8%	3.4 5.7%
Grade 3 Asthenia; Post-Inj. 3	0.0 0%	0.0 0%

Adverse Events

Time Frame	Serious Adverse Events (SAEs) data were collected throughout the study from Day 0 to Year 4, and non-serious Adverse Events were collected for 28 days after each injection.
Adverse Event Reporting Description	Non-related SAEs were collected from Day 0 (post-injection) up to 6 months after the last injection. Related and fatal SAEs were reported from 6 months until the end of study (up to 4 years).
Arm/Group Title	CYD Dengue Vaccine Group		Control Vaccine Group
Arm/Group Description	Participants who received CYD dengue vaccine as first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections. Participants were followed for 4 years after the third injection.		Participants who received the Meningococcal Polysaccharide Vaccine A + C, placebo, and Typhoid Vi polysaccharide vaccine as the first (Day 0), second (Day 0 + 6 months), and third (Day 0 + 12 months) injections, respectively. Participants were followed for 4 years after the third injection.
All Cause Mortality
	CYD Dengue Vaccine Group		Control Vaccine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/120 (0%)		0/60 (0%)
Serious Adverse Events
	CYD Dengue Vaccine Group		Control Vaccine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/120 (2.5%)		3/60 (5%)
Gastrointestinal disorders
Gastritis	1/120 (0.8%)	1	0/60 (0%)	0
Infections and infestations
Dengue fever	1/120 (0.8%)	1	3/60 (5%)	3
Pharyngitis	1/120 (0.8%)	1	0/60 (0%)	0
Other (Not Including Serious) Adverse Events
	CYD Dengue Vaccine Group		Control Vaccine Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	42/120 (35%)		48/60 (80%)
General disorders
Injection site Pain; Post-Any	34/120 (28.3%)	50	48/60 (80%)	77
Injection site Erythema; Post-Any	8/120 (6.7%)	13	13/60 (21.7%)	16
Injection site Swelling; Post-Any	5/119 (4.2%)	5	9/60 (15%)	10
Fever; Post-Any Injection	33/120 (27.5%)	41	16/60 (26.7%)	18
Malaise; Post-Any Injection	35/119 (29.4%)	47	14/60 (23.3%)	20
Asthenia; Post-Any Injection	16/119 (13.4%)	18	3/60 (5%)	3
Infections and infestations
Nasopharyngitis	0/120 (0%)	0	3/60 (5%)	3
Pharyngitis	9/120 (7.5%)	9	7/60 (11.7%)	7
Musculoskeletal and connective tissue disorders
Myalgia; Post-Any Injection	24/119 (20.2%)	34	14/60 (23.3%)	21
Nervous system disorders
Headache; Post-Any Injection	42/119 (35.3%)	63	18/60 (30%)	28

Limitations/Caveats

None reported.

More Information

Certain Agreements

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

Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.