Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Solicited local injection site reactions included pain, itching, erythema, edema and solicited systemic AEs include myalgia, arthralgia, eye pain, photophobia, fatigue, body rash, nausea, vomiting, and fever.

Time frame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)

Population: The safety set included all randomized participants who received at least one dose of study vaccine (or placebo).

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. The severity of all unsolicited AEs was evaluated by the Investigator (using the Common Terminology Criteria for Adverse Events \[CTCAE\] v4.03) as follows. Mild (Grade 1): Transient symptoms, discomfort noticed but was easily tolerated by the participant with no interference to normal daily activities. Moderate (Grade 2): Marked symptoms, moderate interference with participant's daily activities. Severe (Grade 3): Considerable interference with participant's daily activities.

Time frame: Unsolicited AEs were collected within 28 days of all vaccinations. Serious AEs were collected throughout the study up to Day 1080

Population: The safety set included all randomized participants who received at least one dose of study vaccine (or placebo).

Solicited local injection site reactions were collected by subject diary and graded based on the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 for pain \[Grade 0 (no pain), 1 (mild), 2 (moderate) and 3 (severe)\] and itching (pruritus) \[Grade 0 (no itching), 1 (mild), 2 (moderate) and 3 (Severe\]. Severity grade for redness (erythema) and swelling (edema/induration) were derived from recorded length of the longest diameter measurement using the FDA Guidance for Industry: Toxicity Grading Scale of Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trial were Grade 0 (\<2.5 cm), 1 (mild: 2.5-5 cm), 2 (moderate: 5.1-10 cm) and 3 (severe: \>10 cm) and Grade 4 (Potentially Life-threatening: necrosis or exfoliative dermatitis).

Time frame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)

Population: The safety set included all randomized participants who received at least one dose of study vaccine (or placebo). Only categories for which there was at least 1 participant are reported.

Solicited local injection site reactions were collected by subject diary and graded based on the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 for pain \[Grade 0 (no pain), 1 (mild), 2 (moderate) and 3 (severe)\] and itching (pruritus) \[Grade 0 (no itching), 1 (mild), 2 (moderate) and 3 (Severe\]. Severity grade for redness (erythema) and swelling (edema/induration) were derived from recorded length of the longest diameter measurement using the FDA Guidance for Industry: Toxicity Grading Scale of Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trial were Grade 0 (\<2.5 cm), 1 (mild: 2.5-5 cm), 2 (moderate: 5.1-10 cm) and 3 (severe: \>10 cm) and Grade 4 (Potentially Life-threatening: necrosis or exfoliative dermatitis).

Time frame: Within 28 days after either of the vaccination given on Day 0 or 90 (Day 28 for first vaccination, Day 118 for second vaccination)

Population: The safety set included all randomized participants who received at least one dose of study vaccine (or placebo). Only categories for which there was at least 1 participant are reported.

Solicited systemic AEs (headache, muscle pain \[myalgia\], joint pain \[arthralgia\], eye pain, sensitivity to light \[photophobia\], tiredness \[fatigue\], body rash, nausea, were recorded in the participant's-diary along with vomiting \[number of times\]), and body temperature). Diary-recorded severity grades were based on the Common Terminology Criteria for Adverse Events (CTCAE). Severity grades were: Mild (Grade 1): transient symptoms, discomfort noticed but was easily tolerated by the participant with no interference to normal daily activities. Moderate (Grade 2): marked symptoms, moderate interference with participant's daily activities. Severe (Grade 3): Considerable interference with participant's daily activities. The CTCAE severity grades for fever and vomiting were derived from the diary-recorded measurements of temperature level and number of episodes, respectively.

Time frame: Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)

Population: The safety set included all randomized participants who received at least one dose of study vaccine (or placebo). Only categories for which there was at least 1 participant are reported.

Seropositivity rate, defined as the percentage of participants seropositive, was derived from titers of dengue-neutralizing antibodies. Participants were classified by titer after Day 0 as seropositive or seronegative. Seropositive was defined as a MNT50 titre value of ≥10 for any serotype and seronegative was defined as titre value of less than (\<) 10 for all 4 serotypes. Seropositivity was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3, TDV-4.

Time frame: 30 days after second vaccination (Day 120)

Population: FAS included all randomized participants who received at least one dose of study vaccine or placebo and for whom valid pre-dosing and at least one valid post-dosing blood sample has been received.

Time frame: Day 28 and Day 90 (Parts 1 and 2) and Days 120, 180, 360, 720 and 1080 in Part 1

Population: FAS included all randomized participants who received at least one dose of study vaccine or placebo and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received.

GMTs were assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3, and TDV-4.

Time frame: Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1

Population: The FAS included all randomized participants who received at least one dose of study vaccine and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received. Here n is the number of participants with microneutralizing (MN) assay samples.

Dengue fever was assessed in participants who had 3 consecutive days of fever \>38°C and tested positive for dengue virus by polymerase chain reaction (PCR) analysis.

Time frame: Day 1 to Day 1080

Population: The safety set included all randomized participants who received at least one dose of study vaccine (or placebo).

Time frame: Days 0, 7, 14, 90, 97, and 104

Population: Due to the very low prevalence of vaccine viremia, there was insufficient data for the estimation of average titer duration of viral RNA within study groups.

Vaccine viremia was assessed for each of the four vaccine strain serotypes: TDV-1, TDV-2, TDV-3 and TDV-4 for Part-1. Vaccine viral ribonucleic acid (RNA) was detected by a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay.

Time frame: Days 0, 7, 14, 90, 97, and 104

Population: The FAS included all randomized participants who received at least one dose of study vaccine and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received.

Time frame: Days 0, 7, 14, 90, 97, and 104

Population: Due to the very low prevalence of vaccine viremia, there was insufficient data for the estimation of average titer duration of viral RNA within study groups.

Seroconversion rate was defined as the percentage of participants with microneutralization test 50% (MNT50) titer ≥10 or, if the titer on Day 0 was ≥10, a 4-fold rise in antibody titer.

Time frame: Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1

Population: FAS included all randomized participants who received at least one dose of study vaccine or placebo and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received.