Trial Outcomes & Findings for Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Participants (NCT NCT02302066)

Participants took part in the study at 3 investigative sites in Dominican Republic, Panama and Philippines from 05 Dec 2014 to 18 Feb 2019.

Healthy volunteers were enrolled in a 1:2:5:1 ratio into 4 study groups: Group 1 received two doses of Tetravalent Dengue Vaccine (TDV), Group 2 received one dose of TDV, Group 3 received one dose of TDV along with booster vaccination and Group 4 received placebo.

Safety and Immunogenicity of Different Schedules of Takeda's Tetravalent Dengue Vaccine Candidate (TDV) in Healthy Participants

GMTs of neutralizing antibodies were measured by microneutralization test 50% \[MNT50\] for each of the 4 Dengue Serotypes. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4. Data reported for up to Month 48 was collected at Months 1, 3, 6, 12, 13, 18, 24, 36 and 48.

Seropositivity rate, defined as the percentage of participants seropositive, was derived from the titers of dengue-neutralizing antibodies. Seropositivity defined as a reciprocal neutralizing titer ≥10 (for each serotype). The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.

Solicited local injection included pain, erythema at injection site, and swelling at injection site. They were collected using a diary and graded as \[Grade 0 (no pain), 1 (mild: minor reaction to touch), 2 (moderate: cries/protests on touch) and 3 (severe: cries when limb is moved/spontaneously painful)\]. Erythema and Swelling at injection site were graded as Grade 0 (\<10 mm), 1 (mild: ≥10 - ≤ 20 mm), 2 (moderate: \> 20 - ≤ 40 mm) and 3 (severe: \> 40 mm).

Solicited local injection site reactions were collected by participant diary and graded as \[Grade 0 (no pain), 1 (mild: no interference with daily activity), 2 (moderate: interference with daily activity with or without treatment) and 3 (severe: prevents daily activity with or without treatment)\]. Erythema and Swelling at injection site were graded as Grade 0 (\<25 mm), 1 (mild: ≥25 - ≤ 50 mm), 2 (moderate: \> 50 - ≤ 100 mm).

Solicited systemic AEs were collected within 14 days after vaccination using a diary and included drowsiness, graded as 0-behavior as usual, 1-mild: drowsiness easily tolerated, 2-moderate: drowsiness that interferes with normal activity and 3-severe: prevents normal activity with or without treatment; irritability/fussiness, graded as 0-behavior as usual, mild: crying more than usual/no effect on normal activity, moderate: crying more than usual/interferes with normal activity and severe: crying that cannot be comforted/prevents normal; loss of appetite, graded as 0-apetite as usual, mild: eating less than usual/no effect on normal activity, moderate: eating less than usual/interferes with normal activity and severe: not eating at all. A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it.

Solicited systemic AEs were collected by participants within 14 days after vaccination and included headache, asthenia, malaise, myalgia and fever. Severity scales for headache were none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents normal activity with or without treatment. Severity scales for others were none, mild: no interference with daily activity, moderate: interference with daily activity and severe: prevents daily activity. A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it.

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.

An SAE was defined as any untoward medical occurrence or effect that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect or is medically important due to other reasons than the above-mentioned criteria.

Participants with febrile illness (defined as temperature ≥ 38°C on 2 consecutive days) were evaluated for dengue. A dengue infection was considered virologically confirmed by either positive polymerase chain reaction (PCR) or NS1 enzyme-linked immunosorbent assay (ELISA). Virologically confirmed dengue with onset 30 days after first vaccination within each group.