Trial Outcomes & Findings for Study to Evaluate the Immunogenicity, Safety, and Tolerability of a Tick-Borne Encephalitis (TBE) Vaccine in Healthy Japanese Participants 1 Year of Age and Older (NCT NCT04648241)

Last Updated: 2023-11-22

Results Overview

Seropositivity rate based on the immune response was determined by neutralization test (NT). Participants who achieved tick-borne encephalitis virus (TBEV) NT titers \>=1: 10 were considered as seropositive. Exact 2-sided 95% confidence interval (CI) based on the Clopper and Pearson method was presented.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

165 participants

Primary outcome timeframe

4 weeks after Dose 3

Results posted on

2023-11-22

Participant Flow

This study was conducted as part of the Phase 3 clinical development plan to support the use of tick-borne encephalitis (TBE) vaccine 0.5 milliliter (mL) in healthy Japanese adults (greater than or equal to \[\>=\] 16 years old) and 0.25 mL in pediatric participants (\>=1 and less than \[\<\] 16 years old) at investigator sites in Japan.

Participant milestones

Participant milestones
Measure	Adults (>=16 Years Old) Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Overall Study STARTED	100	65
Overall Study COMPLETED	99	65
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Adults (>=16 Years Old) Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Overall Study Lost to Follow-up	1	0

Baseline Characteristics

Study to Evaluate the Immunogenicity, Safety, and Tolerability of a Tick-Borne Encephalitis (TBE) Vaccine in Healthy Japanese Participants 1 Year of Age and Older

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Total n=165 Participants Total of all reporting groups
Age, Continuous	44.3 Years STANDARD_DEVIATION 16.02 • n=5 Participants	6.9 Years STANDARD_DEVIATION 3.89 • n=7 Participants	29.5 Years STANDARD_DEVIATION 22.27 • n=5 Participants
Sex: Female, Male Female	55 Participants n=5 Participants	19 Participants n=7 Participants	74 Participants n=5 Participants
Sex: Female, Male Male	45 Participants n=5 Participants	46 Participants n=7 Participants	91 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	100 Participants n=5 Participants	65 Participants n=7 Participants	165 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	100 Participants n=5 Participants	65 Participants n=7 Participants	165 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 4 weeks after Dose 3

Population: Evaluable immunogenicity (EI) population: Participants who received all 3 doses of the investigational product, had blood drawn for assay testing within the specified time frame for baseline and 4 weeks after the third vaccination, had valid and determinate assay result (NT titer) at baseline and 4 weeks after the third vaccination visit, were NT seronegative at baseline, and had no major protocol violations.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=99 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Seropositive Participants at 4 Weeks After Dose 3	98.0 Percentage of participants Interval 92.9 to 99.8	100 Percentage of participants Interval 94.5 to 100.0	—

PRIMARY outcome

Timeframe: Within 7 days after Dose 1

Population: Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.

LR:participant or legally acceptable representative/parent/legal guardian using an electronic diary (e-diary). LR included redness, swelling and pain at injection site. Redness and swelling were measured using measuring device units. 1 measuring device unit =0.5 centimeter(cm). Redness and swelling were graded as: for participants \>=12 years of age, mild(greater than\[\>\] 2.0 to 5.0 cm), moderate(\>5.0 to 10.0 cm) and severe (\>10.0 cm); for participants less than (\<)12 years of age, mild(\>0 to 2.0 cm), moderate(\>2.0 to7.0 cm) and severe(\>7.0 cm). Pain at the injection site was graded as: for participants \>2 years of age, mild(does not interfere with activity), moderate(interferes with activity) and severe(prevents daily activity); for participants less than or equal to (\<=)2 years of age, mild(hurts if gently touched) moderate(hurts if gently touched with crying) and severe(causes limitation of limb movement). Exact 2-sided 95% CI based on the Clopper and Pearson method was presented.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 Redness: Mild	2.0 Percentage of participants Interval 0.2 to 7.0	3.1 Percentage of participants Interval 0.4 to 10.7	—
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 Redness: Moderate	0 Percentage of participants Interval 0.0 to 3.6	1.5 Percentage of participants Interval 0.0 to 8.3	—
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 Redness: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 Swelling: Mild	3.0 Percentage of participants Interval 0.6 to 8.5	3.1 Percentage of participants Interval 0.4 to 10.7	—
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 Swelling: Moderate	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 Swelling: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 Pain at the injection site: Mild	52.0 Percentage of participants Interval 41.8 to 62.1	36.9 Percentage of participants Interval 25.3 to 49.8	—
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 Pain at the injection site: Moderate	7.0 Percentage of participants Interval 2.9 to 13.9	6.2 Percentage of participants Interval 1.7 to 15.0	—
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1 Pain at the injection site: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 5.5	—

PRIMARY outcome

Timeframe: Within 7 days after Dose 2

Population: Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.

Local reactions were collected by participant or legally acceptable representative/parent/legal guardian using an e-diary. Local reactions included redness, swelling and pain at the injection site. Redness and swelling were measured using measuring device units. 1 measuring device unit =0.5 cm. Redness and swelling were graded as: for participants \>=12 years of age, mild (\> 2.0 to 5.0 cm), moderate (\>5.0 to 10.0 cm) and severe (\>10.0 cm); for participants \<12 years of age, mild (\>0 to 2.0 cm), moderate (\>2.0 to 7.0 cm) and severe (\>7.0 cm). Pain at the injection site was graded as: for participants \>2 years of age, mild (does not interfere with activity), moderate (interferes with activity) and severe (prevents daily activity); for participants \<=2 years of age, mild (hurts if gently touched) moderate (hurts if gently touched with crying) and severe (causes limitation of limb movement). Exact 2-sided 95% CI based on the Clopper and Pearson method was presented.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Local Reactions Within 7 Days After Dose 2 Redness: Mild	0.0 Percentage of participants Interval 0.0 to 3.6	3.1 Percentage of participants Interval 0.4 to 10.7	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 2 Redness: Moderate	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 2 Redness: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 2 Swelling: Mild	0 Percentage of participants Interval 0.0 to 3.6	1.5 Percentage of participants Interval 0.0 to 8.3	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 2 Swelling: Moderate	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 2 Swelling: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 2 Pain at the injection site: Mild	40.0 Percentage of participants Interval 30.3 to 50.3	24.6 Percentage of participants Interval 14.8 to 36.9	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 2 Pain at the injection site: Moderate	4.0 Percentage of participants Interval 1.1 to 9.9	1.5 Percentage of participants Interval 0.0 to 8.3	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 2 Pain at the injection site: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 5.5	—

PRIMARY outcome

Timeframe: Within 7 days after Dose 3

Population: Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product. Here, "Overall Number of Participants Analyzed" signifies participants who were evaluable for this outcome measure.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=99 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Local Reactions Within 7 Days After Dose 3 Redness: Mild	2.0 Percentage of participants Interval 0.2 to 7.1	7.7 Percentage of participants Interval 2.5 to 17.0	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 3 Redness: Moderate	0 Percentage of participants Interval 0.0 to 3.7	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 3 Redness: Severe	0 Percentage of participants Interval 0.0 to 3.7	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 3 Swelling: Mild	1.0 Percentage of participants Interval 0.0 to 5.5	6.2 Percentage of participants Interval 1.7 to 15.0	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 3 Swelling: Moderate	1.0 Percentage of participants Interval 0.0 to 5.5	3.1 Percentage of participants Interval 0.4 to 10.7	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 3 Swelling: Severe	0 Percentage of participants Interval 0.0 to 3.7	0 Percentage of participants Interval 0.0 to 5.5	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 3 Pain at the injection site: Mild	33.3 Percentage of participants Interval 24.2 to 43.5	30.8 Percentage of participants Interval 19.9 to 43.4	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 3 Pain at the injection site: Moderate	3.0 Percentage of participants Interval 0.6 to 8.6	4.6 Percentage of participants Interval 1.0 to 12.9	—
Percentage of Participants With Local Reactions Within 7 Days After Dose 3 Pain at the injection site: Severe	0 Percentage of participants Interval 0.0 to 3.7	0 Percentage of participants Interval 0.0 to 5.5	—

PRIMARY outcome

Timeframe: Within 7 days after Dose 1

Population: Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product. Here, 'Number Analyzed' signifies those participants who were evaluable for the specified rows.

SE:participants or legally acceptable representative/parent/legal guardian using e-diary \& included fever:temperature \>=37.5 degree Celsius(C)\&categorized as 37.5to38.4, 38.5 to 38.9,39.0 to 40.0,\>40.0 degree C.Fatigue, headache, muscle pain, joint pain: mild(didn't interfere with activity), moderate(some interference with activity), severe(prevented daily activity). Vomiting: mild(1-2 times in 24 hours\[hrs\]), moderate(\>2 times in 24hrs), severe(required intravenous hydration). Diarrhea: mild(2-3 loose stools in 24hrs), moderate(4-5 loose stools in 24hrs), severe(6 or more loose stools in 24hrs). Decreased appetite:mild(decreased interest in eating),moderate(decreased oral intake), severe(refusal to feed).Drowsiness: mild(Increased sleeping bouts),moderate(slightly subdued interfering with daily activity),severe(disabling not interested in usual daily activity).Irritability:mild(easily consolable), moderate(required increased attention),severe(inconsolable, crying can't be comforted).

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=57 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) n=8 Participants Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Vomiting: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Diarrhea: Mild	7.0 Percentage of participants Interval 2.9 to 13.9	8.8 Percentage of participants Interval 1.9 to 19.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Diarrhea: Moderate	2.0 Percentage of participants Interval 0.2 to 7.0	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Diarrhea: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Muscle pain: Mild	16.0 Percentage of participants Interval 9.4 to 24.7	5.3 Percentage of participants Interval 1.1 to 14.6	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Muscle pain: Moderate	3.0 Percentage of participants Interval 0.6 to 8.5	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Muscle pain: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Joint pain: Mild	4.0 Percentage of participants Interval 1.1 to 9.9	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Joint pain: Moderate	3.0 Percentage of participants Interval 0.6 to 8.5	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Fever: >=37.5 degree C	2.0 Percentage of participants Interval 0.2 to 7.0	5.3 Percentage of participants Interval 1.1 to 14.6	25.0 Percentage of participants Interval 3.2 to 65.1
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Joint pain: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Decreased appetite: Mild	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Decreased appetite: Moderate	—	—	12.5 Percentage of participants Interval 0.3 to 52.7
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Decreased appetite: Severe	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Fever: 37.5 to 38.4 degree C	2.0 Percentage of participants Interval 0.2 to 7.0	3.5 Percentage of participants Interval 0.4 to 12.1	25.0 Percentage of participants Interval 3.2 to 65.1
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Drowsiness: Mild	—	—	25.0 Percentage of participants Interval 3.2 to 65.1
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Drowsiness: Moderate	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Drowsiness: Severe	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Irritability: Mild	—	—	12.5 Percentage of participants Interval 0.3 to 52.7
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Irritability: Moderate	—	—	12.5 Percentage of participants Interval 0.3 to 52.7
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Irritability: Severe	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Fever: 38.5 to 38.9 degree C	0 Percentage of participants Interval 0.0 to 3.6	1.8 Percentage of participants Interval 0.0 to 9.4	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Fever: 39.0 to 40.0 degree C	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Fever: >40.0 degree C	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Fatigue: Mild	11.0 Percentage of participants Interval 5.6 to 18.8	8.8 Percentage of participants Interval 2.9 to 19.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Fatigue: Moderate	5.0 Percentage of participants Interval 1.6 to 11.3	1.8 Percentage of participants Interval 0.0 to 9.4	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Fatigue: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Headache: Mild	7.0 Percentage of participants Interval 2.9 to 13.9	7.0 Percentage of participants Interval 1.9 to 17.0	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Headache: Moderate	6.0 Percentage of participants Interval 2.2 to 12.6	1.8 Percentage of participants Interval 0.0 to 9.4	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Headache: Severe	0 Percentage of participants Interval 0.0 to 3.6	1.8 Percentage of participants Interval 0.0 to 9.4	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Vomiting: Mild	1.0 Percentage of participants Interval 0.0 to 5.4	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1 Vomiting: Moderate	1.0 Percentage of participants Interval 0.0 to 5.4	0 Percentage of participants Interval 0.0 to 6.3	—

PRIMARY outcome

Timeframe: Within 7 days after Dose 2

SE:participants or a legally acceptable representative/parent/legal guardian using e-diary and included fever:temperature \>=37.5 degreeC \& categorized as 37.5 to 38.4,38.5 to 38.9,39.0 to 40.0,\>40.0 degreeC.Fatigue, headache, muscle pain, joint pain: mild(didn't interfere with activity),moderate(some interference with activity), severe(prevented daily activity). Vomiting: mild(1-2 times in 24 hours\[hrs\]), moderate(\>2 times in 24hrs),severe(required intravenous hydration).Diarrhea: mild(2-3 loose stools in 24hrs), moderate(4-5 loose stools in 24hrs), severe(6 or more loose stools in 24hrs). Decreased appetite: mild(decreased interest in eating), moderate(decreased oral intake), severe(refusal to feed). Drowsiness: mild(Increased sleeping bouts), moderate(slightly subdued interfering with daily activity), severe(disabling not interested in usual daily activity).Irritability: mild(easily consolable), moderate(required increased attention),severe(inconsolable, crying can't be comforted).

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=57 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) n=8 Participants Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Fever: >=37.5 degree C	1.0 Percentage of participants Interval 0.0 to 5.4	7.0 Percentage of participants Interval 1.9 to 17.0	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Fever: 37.5 to 38.4 degree C	1.0 Percentage of participants Interval 0.0 to 5.4	3.5 Percentage of participants Interval 0.4 to 12.1	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Fever: 38.5 to 38.9 degree C	0 Percentage of participants Interval 0.0 to 3.6	3.5 Percentage of participants Interval 0.4 to 12.1	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Fever: 39.0 to 40.0 degree C	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Fever: >40.0 degree C	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Fatigue: Mild	7.0 Percentage of participants Interval 2.9 to 13.9	1.8 Percentage of participants Interval 0.0 to 9.4	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Fatigue: Moderate	1.0 Percentage of participants Interval 0.0 to 5.4	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Fatigue: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Headache: Mild	10.0 Percentage of participants Interval 4.9 to 17.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Headache: Moderate	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Headache: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Vomiting: Mild	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Vomiting: Moderate	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Vomiting: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Diarrhea: Mild	4.0 Percentage of participants Interval 1.1 to 9.9	7.0 Percentage of participants Interval 1.9 to 17.0	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Diarrhea: Moderate	1.0 Percentage of participants Interval 0.0 to 5.4	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Diarrhea: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Muscle pain: Mild	2.0 Percentage of participants Interval 0.2 to 7.0	1.8 Percentage of participants Interval 0.0 to 9.4	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Muscle pain: Moderate	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Muscle pain: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Joint pain: Mild	1.0 Percentage of participants Interval 0.0 to 5.4	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Joint pain: Moderate	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Joint pain: Severe	0 Percentage of participants Interval 0.0 to 3.6	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Decreased appetite: Mild	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Decreased appetite: Moderate	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Decreased appetite: Severe	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Drowsiness: Mild	—	—	12.5 Percentage of participants Interval 0.3 to 52.7
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Drowsiness: Moderate	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Drowsiness: Severe	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Irritability: Mild	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Irritability: Moderate	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 2 Irritability: Severe	—	—	0 Percentage of participants Interval 0.0 to 36.9

PRIMARY outcome

Timeframe: Within 7 days after Dose 3

Systemic events collected by participant using e-diary and included fever defined as temperature \>=37.5 degree C and categorized as 37.5 to 38.4, 38.5 to 38.9, 39.0 to 40.0, \>40.0 degree C. Fatigue, headache, muscle pain, joint pain: mild(didn't interfere with activity), moderate(some interference with activity), severe(prevented daily activity). Vomiting: mild(1-2 times in 24 hours\[hrs\]), moderate(\>2 times in 24hrs), severe(required intravenous hydration). Diarrhea: mild(2-3 loose stools in 24hrs), moderate(4-5 loose stools in 24hrs), severe(6 or more loose stools in 24hrs). Decreased appetite: mild(decreased interest in eating), moderate(decreased oral intake), severe(refusal to feed). Drowsiness: mild(Increased sleeping bouts), moderate(slightly subdued interfering with daily activity), severe(disabling not interested in usual daily activity). Irritability: mild(easily consolable), moderate(required increased attention), severe(inconsolable, crying can't be comforted).

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=99 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=57 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) n=8 Participants Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Fever: >=37.5 degree C	1.0 Percentage of participants Interval 0.0 to 5.5	10.5 Percentage of participants Interval 4.0 to 21.5	12.5 Percentage of participants Interval 0.3 to 52.7
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Fever: 37.5 to 38.4 degree C	0 Percentage of participants Interval 0.0 to 3.7	8.8 Percentage of participants Interval 2.9 to 19.3	12.5 Percentage of participants Interval 0.3 to 52.7
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Fever: 38.5 to 38.9 degree C	1.0 Percentage of participants Interval 0.0 to 5.5	0 Percentage of participants Interval 0.0 to 6.3	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Fever: 39.0 to 40.0 degree C	0 Percentage of participants Interval 0.0 to 3.7	1.8 Percentage of participants Interval 0.0 to 9.4	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Fever: >40.0 degree C	0 Percentage of participants Interval 0.0 to 3.7	0 Percentage of participants Interval 0.0 to 6.3	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Fatigue: Mild	9.1 Percentage of participants Interval 4.2 to 16.6	1.8 Percentage of participants Interval 0.0 to 9.4	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Fatigue: Moderate	2.0 Percentage of participants Interval 0.2 to 7.1	5.3 Percentage of participants Interval 1.1 to 14.6	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Fatigue: Severe	0 Percentage of participants Interval 0.0 to 3.7	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Headache: Mild	9.1 Percentage of participants Interval 4.2 to 16.6	5.3 Percentage of participants Interval 1.1 to 14.6	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Headache: Moderate	1.0 Percentage of participants Interval 0.0 to 5.5	3.5 Percentage of participants Interval 0.4 to 12.1	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Headache: Severe	1.0 Percentage of participants Interval 0.0 to 5.5	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Vomiting: Mild	2.0 Percentage of participants Interval 0.2 to 7.1	1.8 Percentage of participants Interval 0.0 to 9.4	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Vomiting: Moderate	0 Percentage of participants Interval 0.0 to 3.7	1.8 Percentage of participants Interval 0.0 to 9.4	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Vomiting: Severe	0 Percentage of participants Interval 0.0 to 3.7	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Diarrhea: Mild	5.1 Percentage of participants Interval 1.7 to 11.4	5.3 Percentage of participants Interval 1.1 to 14.6	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Diarrhea: Moderate	0 Percentage of participants Interval 0.0 to 3.7	3.5 Percentage of participants Interval 0.4 to 12.1	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Diarrhea: Severe	1.0 Percentage of participants Interval 0.0 to 5.5	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Muscle pain: Mild	3.0 Percentage of participants Interval 0.6 to 8.6	1.8 Percentage of participants Interval 0.0 to 9.4	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Muscle pain: Moderate	1.0 Percentage of participants Interval 0.0 to 5.5	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Muscle pain: Severe	0 Percentage of participants Interval 0.0 to 3.7	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Joint pain: Mild	0 Percentage of participants Interval 0.0 to 3.7	5.3 Percentage of participants Interval 1.1 to 14.6	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Joint pain: Moderate	1.0 Percentage of participants Interval 0.0 to 5.5	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Joint pain: Severe	1.0 Percentage of participants Interval 0.0 to 5.5	0 Percentage of participants Interval 0.0 to 6.3	—
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Decreased appetite: Mild	—	—	12.5 Percentage of participants Interval 0.3 to 52.7
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Decreased appetite: Moderate	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Decreased appetite: Severe	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Drowsiness: Mild	—	—	25.0 Percentage of participants Interval 3.2 to 65.1
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Drowsiness: Moderate	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Drowsiness: Severe	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Irritability: Mild	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Irritability: Moderate	—	—	0 Percentage of participants Interval 0.0 to 36.9
Percentage of Participants With Systemic Events Within 7 Days After Dose 3 Irritability: Severe	—	—	0 Percentage of participants Interval 0.0 to 36.9

PRIMARY outcome

Timeframe: Within 1 month after Dose 1

Population: Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.

An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention. Exact 2-sided 95% CI based on the Clopper and Pearson method was presented.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Dose 1	6.0 Percentage of participants Interval 2.2 to 12.6	21.5 Percentage of participants Interval 12.3 to 33.5	—

PRIMARY outcome

Timeframe: Within 1 month after Dose 2

Population: Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Dose 2	2.0 Percentage of participants Interval 0.2 to 7.0	10.8 Percentage of participants Interval 4.4 to 20.9	—

PRIMARY outcome

Timeframe: Within 1 month after Dose 3

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=99 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Dose 3	6.1 Percentage of participants Interval 2.3 to 12.7	29.2 Percentage of participants Interval 18.6 to 41.8	—

PRIMARY outcome

Timeframe: Within 1 month after any Dose

Population: Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Any Dose	14.0 Percentage of participants Interval 7.9 to 22.4	41.5 Percentage of participants Interval 29.4 to 54.4	—

PRIMARY outcome

Timeframe: From Day 1 up to end of study (up to approximately 13 months)

Population: Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.

An SAE was defined as any untoward medical occurrence that, at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect or that is considered to be an important medical event. Percentage of participants with SAEs and the exact 2-sided 95% CI based on the Clopper and Pearson method was presented.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Serious Adverse Events (SAEs) Throughout the Study	2.0 Percentage of participants Interval 0.2 to 7.0	1.5 Percentage of participants Interval 0.0 to 8.3	—

SECONDARY outcome

Timeframe: 4 weeks after Dose 2

Population: Evaluable immunogenicity (EI) population for the second dose: Participants who received the first 2 doses of the investigational product, had blood drawn for assay testing within the specified time frame for baseline and 4 weeks after the second vaccination, had valid and determinate assay result (NT titer) at baseline and 4 weeks after the second vaccination visit, were NT seronegative at baseline, and had no major protocol violations.

Seropositivity rate based on the immune response was determined by NT. Participants who achieved TBEV NT titers \>=1: 10 were considered as seropositive. Exact 2-sided 95% CI based on the Clopper and Pearson method was presented.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Seropositive Participants at 4 Weeks After Dose 2	93 Percentage of participants Interval 86.1 to 97.1	92.3 Percentage of participants Interval 83.0 to 97.5	—

SECONDARY outcome

Timeframe: 4 weeks after Dose 2 and Dose 3

Population: EI population: Participants who received all 3 doses of the investigational product, had blood drawn for assay testing within specified time frame for baseline and 4 weeks after the third vaccination, had valid and determinate assay result (NT titer) at baseline and 4 weeks after the third vaccination visit, were NT seronegative at baseline, and had no major protocol violations.

GMTs and associated 2-sided 95% CIs were calculated as the mean of the assay results on the natural logarithmic scale based on Student's t distribution and then exponentiating the results. The lower limit of quantitation (LLOQ) value for NT was 5. Assay results below the LLOQ were set to 0.5 × LLOQ.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=99 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Geometric Mean Titers (GMTs) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 2 and Dose 3 4 Weeks after Dose 2	28.2 Titer Interval 23.5 to 33.8	29.4 Titer Interval 23.3 to 37.0	—
Geometric Mean Titers (GMTs) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 2 and Dose 3 4 Weeks after Dose 3	80.1 Titer Interval 65.1 to 98.5	233.1 Titer Interval 187.9 to 289.1	—

SECONDARY outcome

Timeframe: From Baseline to 4 weeks after Dose 2

Population: Evaluable immunogenicity population for the second dose: Participants who received the first 2 doses of the investigational product, had blood drawn for assay testing within the specified time frame for baseline and 4 weeks after the second vaccination, had valid and determinate assay result (NT titer) at baseline and 4 weeks after the second vaccination visit, were NT seronegative at baseline, and had no major protocol violations.

GMFRs and the corresponding 2-sided 95% CIs were calculated by exponentiating the mean logarithm of fold rises and the corresponding CIs (based on the Student t distribution). The LLOQ value for NT was 5. Assay results below the LLOQ were set to 0.5 × LLOQ.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=100 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Geometric Mean Fold Rise (GMFR) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 2 as Compared to Baseline	11.2 Fold rise Interval 9.3 to 13.4	11.8 Fold rise Interval 9.3 to 14.8	—

SECONDARY outcome

Timeframe: From Baseline to 4 weeks after Dose 3

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=99 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Geometric Mean Fold Rise (GMFR) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 3 as Compared to Baseline	32.0 Fold rise Interval 26.0 to 39.4	93.2 Fold rise Interval 75.2 to 115.6	—

SECONDARY outcome

Timeframe: From 4 weeks after Dose 2 to 4 weeks after Dose 3

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=99 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Geometric Mean Fold Rise (GMFR) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 3 as Compared to 4 Weeks After Dose 2	2.8 Fold rise Interval 2.3 to 3.5	7.9 Fold rise Interval 6.2 to 10.2	—

SECONDARY outcome

Timeframe: Before Dose 1, 4 weeks after Dose 2, Before Dose 3 and 4 weeks after Dose 3

The LLOQ value for NT was 5. Assay results below the LLOQ were set to 0.5 × LLOQ. Percentage of participants with NT\>=LLOQ and exact 2-sided 95% CI based on the Clopper and Pearson method was presented.

Outcome measures

Outcome measures
Measure	Adults (>=16 Years Old) n=99 Participants Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 Participants Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to 2 Years Old) Participants aged 1 to 2 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Percentage of Participants With Neutralizing Antibody Titers >= Lower Limit of Quantification (LLOQ) 4 Weeks after Dose 3	99.0 Percentage of Participants Interval 94.5 to 100.0	100.0 Percentage of Participants Interval 94.5 to 100.0	—
Percentage of Participants With Neutralizing Antibody Titers >= Lower Limit of Quantification (LLOQ) Before Dose 1	0 Percentage of Participants Interval 0.0 to 3.7	0 Percentage of Participants Interval 0.0 to 5.5	—
Percentage of Participants With Neutralizing Antibody Titers >= Lower Limit of Quantification (LLOQ) 4 Weeks after Dose 2	96.0 Percentage of Participants Interval 90.0 to 98.9	98.5 Percentage of Participants Interval 91.7 to 100.0	—
Percentage of Participants With Neutralizing Antibody Titers >= Lower Limit of Quantification (LLOQ) Before Dose 3	63.6 Percentage of Participants Interval 53.4 to 73.1	86.2 Percentage of Participants Interval 75.3 to 93.5	—

Adverse Events

Adults (>=16 Years Old)

Serious events: 2 serious events

Other events: 76 other events

Deaths: 0 deaths

Pediatric (1 to <16 Years Old)

Serious events: 1 serious events

Other events: 59 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Adults (>=16 Years Old) n=100 participants at risk Participants aged \>=16 years old received three doses of 0.5 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.	Pediatric (1 to <16 Years Old) n=65 participants at risk Participants aged 1 to \<16 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Participants were followed up for safety for 21-35 days after Dose 3.
Gastrointestinal disorders Abdominal pain	1.0% 1/100 • All-Cause mortality and SAEs: from Day 1 up to end of study (up to approximately 13 months); Other AEs (non-systematic assessment): up to 1 month after each Dose; Local reactions and systemic events (systematic assessment, included in other AEs): within 7 days after each Dose Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.	0.00% 0/65 • All-Cause mortality and SAEs: from Day 1 up to end of study (up to approximately 13 months); Other AEs (non-systematic assessment): up to 1 month after each Dose; Local reactions and systemic events (systematic assessment, included in other AEs): within 7 days after each Dose Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.
Gastrointestinal disorders Colitis ischaemic	1.0% 1/100 • All-Cause mortality and SAEs: from Day 1 up to end of study (up to approximately 13 months); Other AEs (non-systematic assessment): up to 1 month after each Dose; Local reactions and systemic events (systematic assessment, included in other AEs): within 7 days after each Dose Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.	0.00% 0/65 • All-Cause mortality and SAEs: from Day 1 up to end of study (up to approximately 13 months); Other AEs (non-systematic assessment): up to 1 month after each Dose; Local reactions and systemic events (systematic assessment, included in other AEs): within 7 days after each Dose Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.
Gastrointestinal disorders Diarrhoea	0.00% 0/100 • All-Cause mortality and SAEs: from Day 1 up to end of study (up to approximately 13 months); Other AEs (non-systematic assessment): up to 1 month after each Dose; Local reactions and systemic events (systematic assessment, included in other AEs): within 7 days after each Dose Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.	1.5% 1/65 • All-Cause mortality and SAEs: from Day 1 up to end of study (up to approximately 13 months); Other AEs (non-systematic assessment): up to 1 month after each Dose; Local reactions and systemic events (systematic assessment, included in other AEs): within 7 days after each Dose Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event. Safety analysis population included all enrolled participants who received at least 1 dose of the investigational product.

Other adverse events

Additional Information

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Results disclosure agreements

Principal investigator is a sponsor employee Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
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