Dengue
Conditions
Keywords
Dengue, Vaccine, Thailand
Brief summary
The main target populations for the tetravalent live attenuated dengue virus vaccine are indigenous populations, especially infants less than 2 years old, residing in areas of the world endemic for dengue and at risk of developing dengue hemorrhagic fever (DHF). The presence of maternal dengue antibody during the first year of life makes it unlikely that a vaccine given during that time will have long-term efficacy, as the vaccine virus would likely be neutralized prior to necessary replication. Children older than 18 months may have preexisting flavivirus antibody. Therefore, vaccination of infants living in Thailand early in the second year of life (between the ages of 12 and 18 months) seems most beneficial. The aim of this trial is to evaluate the safety and immunogenicity of a two-dose schedule of a tetravalent live attenuated dengue vaccine in flavivirus antibody naïve infants beginning at 12-15 months of age. * To assess the kinetics of dengue neutralizing antibodies to each dengue virus serotype one and four years following dose 2 of dengue/control vaccination in the setting of potential wild-type dengue virus exposure. * To assess the immunogenicity, the safety and reactogenicity of a booster dose of dengue vaccine administered at Year 3 following primary vaccination.
Detailed description
* This is a Phase I/II, randomized, observer-blind, controlled trial. Thirty-four flavivirus naïve infants will be randomized to the vaccine group and 17 infants to the control group. * Infants receive dengue vaccine at study months 0 and 6 or control vaccine (Varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both are licensed for use in Thailand. * All infants subsequently receive an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. * Infants are monitored daily for 21 days following each dengue or control vaccination and 7 days after each JE vaccination for solicited adverse events. Unsolicited events will be recorded up to 31 days (days 0-30) after dengue/control vaccinations and each day after dose 1 of JE vaccine until the concluding study visit. * Study duration (excluding screening) is approximately 8.5 months for each subject. * Each enrollee is followed a four year period following dose 2 of dengue/control vaccination to assess for dengue-related hospitalizations and dengue antibody kinetics. * Investigators will administer a 3rd dose of tetravalent dengue vaccine to all subjects who received 2 doses of dengue vaccine (0 and 6 months) during the primary phase of the study. The 3rd dose will be administered 3 years following the primary vaccination series. Peripheral blood mononuclear cells (PBMCs) and sera will be collected at the time of dose 3, and twice again at one month and one year following dose 3 from dengue group subjects. Investigators will address the following questions: 1. Is a 3rd dose of live virus tetravalent dengue vaccine safe in Thai toddlers/children? 2. Is a 3rd dose of live virus tetravalent dengue vaccine required in toddlers/children to induce optimal immune (neutralizing antibody, cellular mediated immunity) responses? 3. Is there evidence of T and B cell memory following a primary dengue vaccination series (dose 1 and 2)? 4. How does a 3rd dose of live virus tetravalent dengue vaccine impact B and T cell memory?
Interventions
BIOLOGICALTetravalent live attenuated dengue vaccine
DEN candidate vaccine: One dose of the tetravalent, live attenuated DEN vaccine candidate, F17, contains dengue serotype 1, 2, 3 and 4 vaccines. This formulation contains 50 mcg/mL neomycin base, 5.5% lactose, and 1.9 g/dL human serum albumin; for subcutaneous injection. Infants received dengue vaccine at study months 0 and 6 or control vaccine (varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both control vaccines are licensed for use in Thailand. All infants subsequently received an inactivated JE vaccine approximately one and 1.5 months following dengue vaccine dose 2. The licensed JE vaccine in liquid form, was dosed at 0.25 ml for subcutaneous injection. A booster dose of DEN vaccine was given to all subjects previously vaccinated with DEN vaccine in Dengue -001. The booster dose was administered approximately 42 months after dose 2 (at the Year 3 visit).
BIOLOGICALVaricella vaccine and Haemophilus influenzae Type b Conjugate vaccine
Infants received dengue vaccine at study months 0 and 6 or control vaccine (varicella vaccine at study month 0 and Haemophilus influenzae Type b Conjugate vaccine at study month 6). Both control vaccines are licensed for use in Thailand.
Sponsors
GlaxoSmithKline
U.S. Army Medical Research and Development Command
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
12 Months to 15 Months
Healthy volunteers
Yes
Inclusion criteria
* Male and female infants between 12 and 15 months (12 and \<16 months) of age at the time of the first dengue vaccination * Free of obvious health problems as established by medical history and clinical examination before entering into the study. As a marker of nutritional status, an infant's weight to height ratio will be above the 5th percentile compared to the standards for same sex and age children cared for at Phramongkutklao Hospital, Bangkok, Thailand * Written informed consent obtained from the parent of the subject. Amendment 8 Inclusion Criteria: * Completed the Dengue-001 study having previously received 2 doses of experimental dengue vaccine according to protocol. * Written informed consent obtained from the parent or guardian of the subject. (obtained in amendment 5) * Written informed consent obtained from the parent or guardian of the subject who agrees to their child's participation to receive a dengue booster dose and booster follow-up.
Exclusion criteria
* Use of any investigational or non-registered drug or vaccine other than the protocol-specified vaccines within 30 days preceding the administration of the first dose of dengue/control vaccine or planned use during the study period * Administration of a registered vaccine within 30 days preceding the first study vaccination or planned administration within 30 days prior to, or 30 days after any protocol-specified vaccine administration * MMR vaccination given within 60 days prior to the first dose of dengue/control vaccine (added bullet point, or planned administration within 60 days prior to, or 30 days after any protocol-specified vaccine administration * Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs during the study period. (For corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. Inhaled and topical steroids are allowed. * Any confirmed or suspected immunosuppressive or immunodeficient condition * Any clinically significant history, including any seizures or other serious medical condition as determined by the investigator * A first order family member (parent or sibling) with a history of chronic headaches * A first order family member (parent or sibling) with a history of a congenital or hereditary immunodeficiency * Abnormal clinical laboratory screening test results (based on normal values set by the laboratory) that are deemed clinically significant by study investigators and/or the Medical Monitor * The presence of HBsAg or antibodies against HIV or HCV at screening * Pre-existing antibody to dengue 1-4 virus serotypes or Japanese encephalitis virus (JEV) by HAI or PRNT50 at screening * Previous vaccination against yellow fever virus, JEV, tick-borne encephalitis virus (TBE), varicella virus or booster dose of Hib in the second year of life * History of varicella disease or invasive Haemophilus Influenzae B disease * Acute disease at time of enrollment (Acute illness is defined as the presence of a moderate or severe illness with or without fever). All vaccines can be administered to persons with a minor illness such as diarrhea or mild upper respiratory infection with or without low-grade febrile illness, i.e., axillary temperature \<37.5°C (\<99.5°F). * Administration of immunoglobulins and/or blood products since birth or planned administration during the study period * Known allergic or idiosyncratic reaction to neomycin or related antibiotics (including streptomycin, gentamicin, amikacin, , tobramycin, kanamycin and bacitracin) * Allergy to dogs or monkeys or hypersensitivity to proteins of rodent or neural origin * Allergy to gelatin or hypersensitivity to thimerosal * Infant whose parent has no easy access to a fixed or mobile telephone * Parental illiteracy * Plans to leave Bangkok during the first 8.5 months after initial vaccination or definite plans to move from Bangkok during the 5 years following first dose dengue/control vaccination. Amendment 8
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | 30 days post Dose 2 | Assess the immunogenicity of the dengue vaccine in terms of GMTs 30 days post-Dose 2 of dengue vaccine for all four serotypes (DEN-1, 2, 3, 4 and JE (Japanese encephalitis)). Analysis of immunogenicity was performed on the ATP cohort. |
| Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | month 8.5 | Seropositivity for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2 (and 2 doses of JE). Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination. |
| JE Vaccine Response | Pre-vaccination, 1, 6, 7 and 8.5 months after two doses of dengue vaccine | Seropositivity rates and GMTs for N lg to JEV antibodies. Pre= Pre vaccination, blood sampling prior to the first vaccine dose; PI(M1)= Post 1, month 1, blood sampling one month after dose 1 at study month 1; PI(M6)= Post 1, month 6, blood sampling 6 months after dose 1 at study month 6; PII(M7)= Post II, month 7, blood sampling one month after dose 2 at study month 7; PIV(M8.5)= Post IV, month 8.5, blood sampling after 2 doses of dengue/control and 2 doses of JE vaccines at study month 8.5 |
| Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | 21-day follow-up period after Dose 1 | Local and general solicited reactogenicity using diary cards for 21 days (days 0-20) after the first dose of dengue/control vaccine |
| Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | month 7 after dose 2 | Seronegative for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2. Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose | 10 days after post dose 1 and 2 | Percentage of subjects with a dengue viremia 10 days after each dose of vaccine. RT PCR = Reverse-transcriptase polymerase chain reaction Nested PCR - Nested polymerase chain reaction Per protocol, all participants receiving a Dengue Vaccine were combined for Dengue Viremia assessment via RT-PCR and Nested PCR |
| Incidence of Dengue Specific Symptoms | 30-day follow-up period after dose 1 and 2 | Percentage of subjects showing incidence of dengue specific symptoms during the 30-day follow-up period after vaccinations |
Countries
Thailand
Participant flow
Recruitment details
51 infants enrolled and vaccinated for safety cohort, all received dose 1 and 50 completed the study. 49 vaccinated for ATP immunogenicity cohort.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A - 1/10th Dose Dengue Vaccine 1/10th full dose at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6) | 4 |
| Cohort B - Full Dose Dengue Vaccine Full-dose of dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6) | 10 |
| Cohort C - Full Dose Dengue Vaccine Full-dose dengue vaccine at study months 0 and 6 or control vaccines (varicells vaccine at study month 0 and Hib vaccine at study month 6) | 20 |
| Control Group - Hib Vaccine Hemophilus influenza type b (Hib) vaccine and varicella vaccine | 17 |
| Total | 51 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Infected with Dengue during study | 0 | 1 | 0 | 0 |
| Overall Study | Moved out of area | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort A - 1/10th Dose Dengue Vaccine | Cohort B - Full Dose Dengue Vaccine | Cohort C - Full Dose Dengue Vaccine | Control Group - Hib Vaccine | Total |
|---|---|---|---|---|---|
| Age, Continuous | 14.0 months STANDARD_DEVIATION 0 | 13.3 months STANDARD_DEVIATION 0.82 | 13.6 months STANDARD_DEVIATION 0.88 | 13.6 months STANDARD_DEVIATION 0.79 | 13.6 months STANDARD_DEVIATION 0.8 |
| Race/Ethnicity, Customized Southeast Asian | 4 Participants | 10 Participants | 20 Participants | 17 Participants | 51 Participants |
| Region of Enrollment Thailand | 4 participants | 10 participants | 20 participants | 17 participants | 51 participants |
| Sex: Female, Male Female | 1 Participants | 6 Participants | 7 Participants | 9 Participants | 23 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 13 Participants | 8 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 10 | 0 / 20 | 0 / 17 |
| other Total, other adverse events | 4 / 4 | 10 / 10 | 20 / 20 | 6 / 17 |
| serious Total, serious adverse events | 0 / 4 | 1 / 10 | 0 / 20 | 3 / 17 |
Outcome results
Primary
Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine
Assess the immunogenicity of the dengue vaccine in terms of GMTs 30 days post-Dose 2 of dengue vaccine for all four serotypes (DEN-1, 2, 3, 4 and JE (Japanese encephalitis)). Analysis of immunogenicity was performed on the ATP cohort.
Time frame: 30 days post Dose 2
Population: GMT calculated on all subjects. Dil = Dilution; P1(M1) = blood sampling on month after dose 1, at study month 1; PII(M7) = blood sampling one month after dose 2, at study month 7; PII(M8.5) = blood sampling 2 1/2 months after dose 2, at study month 8.5. Combining of cohorts B and C was due to both cohorts being full dose
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-4 GMT PII(M7) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-3 GMT - PI(M1) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | JE Vaccine GMT PII(M7) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-4 GMT PI(M1) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-3 GMT PII(M7) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-1 GMT - PI(M1) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-2 GMT - PI(M1) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-1 GMT - PII(M7) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | JE Vaccine GMT PI(M1) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-2 GMT - PII(M7) | 5.0 titers |
| Control Group - Hib Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | JE Vaccine GMT PII(M8.5) | 16.8 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-3 GMT PII(M7) | 5.0 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-1 GMT - PI(M1) | 5.0 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-1 GMT - PII(M7) | 6.1 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-2 GMT - PI(M1) | 8.8 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-2 GMT - PII(M7) | 173.6 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-3 GMT - PI(M1) | 5.0 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-4 GMT PI(M1) | 15.7 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-4 GMT PII(M7) | 31.9 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | JE Vaccine GMT PI(M1) | 5.0 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | JE Vaccine GMT PII(M7) | 5.0 titers |
| Cohort A - 1/10th Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | JE Vaccine GMT PII(M8.5) | 19.3 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | JE Vaccine GMT PII(M7) | 8.3 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-4 GMT PII(M7) | 52.5 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-2 GMT - PI(M1) | 13.7 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-1 GMT - PI(M1) | 5.2 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | JE Vaccine GMT PI(M1) | 6.0 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-1 GMT - PII(M7) | 20.7 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-3 GMT PII(M7) | 29.2 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-3 GMT - PI(M1) | 5.0 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | JE Vaccine GMT PII(M8.5) | 12.9 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-4 GMT PI(M1) | 22.5 titers |
| Cohorts B & C - Full Dose Dengue Vaccine | Geometric Mean Titers (GMT) for N Antibody to All Four Serotypes and Japanese Encephalitis (JE) Vaccine | DEN-2 GMT - PII(M7) | 239.6 titers |
Primary
JE Vaccine Response
Seropositivity rates and GMTs for N lg to JEV antibodies. Pre= Pre vaccination, blood sampling prior to the first vaccine dose; PI(M1)= Post 1, month 1, blood sampling one month after dose 1 at study month 1; PI(M6)= Post 1, month 6, blood sampling 6 months after dose 1 at study month 6; PII(M7)= Post II, month 7, blood sampling one month after dose 2 at study month 7; PIV(M8.5)= Post IV, month 8.5, blood sampling after 2 doses of dengue/control and 2 doses of JE vaccines at study month 8.5
Time frame: Pre-vaccination, 1, 6, 7 and 8.5 months after two doses of dengue vaccine
Population: Combining of cohorts B and C was due to both cohorts being full dose
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Control Group - Hib Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PRE | 0.0 % of subjects with titer within range |
| Control Group - Hib Vaccine | JE Vaccine Response | GMT - PRE | 5.0 % of subjects with titer within range |
| Control Group - Hib Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PI(M1) | 0.0 % of subjects with titer within range |
| Control Group - Hib Vaccine | JE Vaccine Response | GMT - PI(M1) | 5.0 % of subjects with titer within range |
| Control Group - Hib Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PI(M6) | 6.3 % of subjects with titer within range |
| Control Group - Hib Vaccine | JE Vaccine Response | GMT - PI(M6) | 5.3 % of subjects with titer within range |
| Control Group - Hib Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PII(M7) | 0.0 % of subjects with titer within range |
| Control Group - Hib Vaccine | JE Vaccine Response | GMT - PII(M7) | 5.0 % of subjects with titer within range |
| Control Group - Hib Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PIV(M8.5) | 56.3 % of subjects with titer within range |
| Control Group - Hib Vaccine | JE Vaccine Response | GMT - PIV(M8.5) | 16.8 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PIV(M8.5) | 100 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PRE | 0.0 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | GMT - PI(M6) | 5.0 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PI(M6) | 0.0 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | GMT - PRE | 5.0 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | GMT - PIV(M8.5) | 19.3 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | GMT - PII(M7) | 5.0 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PI(M1) | 0.0 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PII(M7) | 0.0 % of subjects with titer within range |
| Cohort A - 1/10th Dose Dengue Vaccine | JE Vaccine Response | GMT - PI(M1) | 5.0 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | GMT - PII(M7) | 8.3 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | GMT - PI(M1) | 6.0 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PI(M6) | 0.0 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | GMT - PI(M6) | 5.0 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PIV(M8.5) | 32.1 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PII(M7) | 17.9 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PRE | 0.0 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | GMT - PIV(M8.5) | 12.9 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | GMT - PRE | 5.0 % of subjects with titer within range |
| Cohorts B & C - Full Dose Dengue Vaccine | JE Vaccine Response | N lg against JEV >10 1/Dil - PI(M1) | 13.8 % of subjects with titer within range |
Primary
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE
Seropositivity for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2 (and 2 doses of JE). Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
Time frame: month 8.5
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Control Group - Hib Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-4 (Dil) | 50.0 % of responders |
| Control Group - Hib Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-2 (Dil) | 100 % of responders |
| Control Group - Hib Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-3 (Dil) | 25.0 % of responders |
| Control Group - Hib Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-1 (Dil) | 25.0 % of responders |
| Cohort A - 1/10th Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-4 (Dil) | 88.9 % of responders |
| Cohort A - 1/10th Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-3 (Dil) | 77.8 % of responders |
| Cohort A - 1/10th Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-2 (Dil) | 100 % of responders |
| Cohort A - 1/10th Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-1 (Dil) | 55.6 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-4 (Dil) | 60.0 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-2 (Dil) | 100 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-3 (Dil) | 60.0 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-1 (Dil) | 35.0 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-4 (Dil) | 69.0 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-2 (Dil) | 100 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-1 (Dil) | 41.4 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dengue Dose 2 (and 2 Doses of JE | N lg to DEN-3 (Dil) | 65.5 % of responders |
Primary
Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2
Seronegative for N antibody against DEN 1, 2, 3 and 4 antibody after dengue dose 2. Seronegative (antibody titer \<10 1/Dil for N lg to DEN-1, N lg to DEN-2, N lg to DEN-3, N lg) prior to vaccination.
Time frame: month 7 after dose 2
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Control Group - Hib Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-1 (Dil) | 25.0 % of responders |
| Control Group - Hib Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-2 (Dil) | 100 % of responders |
| Control Group - Hib Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-3 (Dil) | 0.0 % of responders |
| Control Group - Hib Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-4 (Dil) | 75.0 % of responders |
| Cohort A - 1/10th Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-2 (Dil) | 100 % of responders |
| Cohort A - 1/10th Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-3 (Dil) | 100 % of responders |
| Cohort A - 1/10th Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-4 (Dil) | 100 % of responders |
| Cohort A - 1/10th Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-1 (Dil) | 88.9 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-3 (Dil) | 80.0 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-2 (Dil) | 100 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-4 (Dil) | 94.7 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-1 (Dil) | 40.0 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-4 (Dil) | 96.4 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-2 (Dil) | 100 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-1 (Dil) | 55.2 % of responders |
| Cohorts B & C - Full Dose Dengue Vaccine | Percent of Participants With Seronegative Neutralizing (N) Antibody Titers to Each DEN Serotype After Dose 2 | N lg to DEN-3 (Dil) | 86.2 % of responders |
Primary
Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine.
Local and general solicited reactogenicity using diary cards for 21 days (days 0-20) after the first dose of dengue/control vaccine
Time frame: 21-day follow-up period after Dose 1
Population: Format of results is consistent with how data was presented in the Final Clinical Study Report. Combining of cohorts B and C was due to both cohorts being full dose
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 1 : Redness | 1 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Decreased activity | 11 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose : Redness | 4 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 1 : Pain | 3 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Cough | 15 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose : Swelling | 3 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 2 : Pain | 2 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / subject : Swelling | 2 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / subject : Pain | 3 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Vomiting | 12 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / subject : Redness | 3 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Loss of appetite | 13 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 2 : Redness | 3 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Fever (axillary celsius) | 16 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Irritability | 13 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 2 : Swelling | 1 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 1 : Swelling | 2 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Drowsiness | 12 specified events |
| Control Group - Hib Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose : Pain | 5 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Loss of appetite | 2 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 1 : Pain | 1 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 1 : Redness | 2 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 1 : Swelling | 1 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 2 : Pain | 1 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 2 : Redness | 1 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 2 : Swelling | 1 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose : Pain | 2 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose : Redness | 3 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose : Swelling | 2 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / subject : Pain | 1 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / subject : Redness | 2 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / subject : Swelling | 1 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Cough | 4 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Decreased activity | 2 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Drowsiness | 0 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Irritability | 3 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Fever (axillary celsius) | 3 specified events |
| Cohort A - 1/10th Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Vomiting | 2 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Cough | 27 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose : Pain | 24 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Vomiting | 24 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Decreased activity | 11 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 2 : Swelling | 8 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Fever (axillary celsius) | 24 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Drowsiness | 18 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 2 : Redness | 13 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 1 : Pain | 11 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Irritability | 23 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 2 : Pain | 13 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / subject : Pain | 18 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 1 : Swelling | 16 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / subject : Redness | 22 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose : Swelling | 24 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose - Loss of appetite | 21 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / subject : Swelling | 19 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Overall / dose : Redness | 34 specified events |
| Cohorts B & C - Full Dose Dengue Vaccine | Reactogenicity in Terms of Solicited Symptoms After Dose 1 of the Dengue Vaccine vs. Control Vaccine. | Dose 1 : Redness | 21 specified events |
Secondary
Incidence of Dengue Specific Symptoms
Percentage of subjects showing incidence of dengue specific symptoms during the 30-day follow-up period after vaccinations
Time frame: 30-day follow-up period after dose 1 and 2
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Mucosal hemorrhage | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival injection | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Rash | 5.9 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Lymphadenopathy | 70.6 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Splenomegaly | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Rash | 11.8 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival injecgtion | 5.9 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Mucosal hemorrhage | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Lymphadenopathy | 58.8 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Control Group - Hib Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Spenomegaly | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Lymphadenopathy | 75.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Rash | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Splenomegaly | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Mucosal hemorrhage | 25.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival injection | 0.00 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Rash | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Mucosal hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Lymphadenopathy | 50.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Spenomegaly | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival injecgtion | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohort A - 1/10th Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Lymphadenopathy | 60.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival injection | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Mucosal hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Lymphadenopathy | 80.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Splenomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Rash | 10.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival injecgtion | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Mucosal hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Rash | 30.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Spenomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Spenomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Lymphadenopathy | 25.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival injecgtion | 15.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Lymphadenopathy | 50.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Mucosal hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival injection | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Rash | 15.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Splenomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Mucosal hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Rash | 5.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Mucosal hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Mucosal hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Splenomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Spenomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Lymphadenopathy | 60.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Rash | 6.7 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Rash | 20.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Conjunctival injecgtion | 10.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Hepatomegaly | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 2 - Lymphadenopathy | 36.7 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival injection | 0.0 % of subjects with specified symptoms |
| Cohorts B & C - Full Dose Dengue Vaccine | Incidence of Dengue Specific Symptoms | Dose 1 - Conjunctival hemorrhage | 0.0 % of subjects with specified symptoms |
Secondary
Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose
Percentage of subjects with a dengue viremia 10 days after each dose of vaccine. RT PCR = Reverse-transcriptase polymerase chain reaction Nested PCR - Nested polymerase chain reaction Per protocol, all participants receiving a Dengue Vaccine were combined for Dengue Viremia assessment via RT-PCR and Nested PCR
Time frame: 10 days after post dose 1 and 2
Population: All participants with evaluable results are reported via RT-PCR and Nested PCR analysis. Scheduled phlebotomy and unscheduled phlebotomy when a subject was ill during the study revealed dengue viremia by RT-/nested PCR, for seven subjects (2 in cohort B and 5 in cohort C).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control Group - Hib Vaccine | Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose | 10 days post dose 1 | 2.9 % of subjects |
| Control Group - Hib Vaccine | Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose | 10 days post dose 2 | 0.0 % of subjects |
| Cohort A - 1/10th Dose Dengue Vaccine | Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose | 10 days post dose 1 | 14.7 % of subjects |
| Cohort A - 1/10th Dose Dengue Vaccine | Percentage of Subjects With a Dengue Viremia 10 Days Post Booster Dose | 10 days post dose 2 | 5.9 % of subjects |