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

A PHASE 3, SINGLE-ARM, OPEN-LABEL STUDY TO EVALUATE THE IMMUNOGENICITY, SAFETY, AND TOLERABILITY OF A TICK-BORNE ENCEPHALITIS VACCINE IN HEALTHY JAPANESE PARTICIPANTS 1 YEAR OF AGE AND OLDER

The main purpose of this study is to provide safety and immunogenicity data in Japanese participants.

Study Overview

• Status: Completed
• Conditions: Tick-Borne Encephalitis
• Intervention / Treatment: Biological: TBE vaccine 0.5 mL; Biological: TBE vaccine 0.25 mL

• Study Type: Interventional
• Enrollment (Actual): 165
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukuoka
    • Fukuoka,, Fukuoka, Japan, 812-0025
      • Medical Co. LTA PS Clinic
  • Hokkaido
    • Ebetsu Shi, Hokkaido, Japan, 069-0816
      • Azuma kodomo katei clinic
    • Sapporo, Hokkaido, Japan, 006-0831
      • Watanabe Pediatric Allergy Clinic
    • Sapporo, Hokkaido, Japan, 062-0907
      • Ohigesenseino Kodomo Clinic
    • Sapporo, Hokkaido, Japan, 063-0841
      • SUZURAN Children's Clinic
  • Yamanashi
    • Kofu-city, Yamanashi, Japan, 400-0853
      • Childrens clinic of Kose

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Japanese male or female participants ≥1 years old at Visit 1.
• Participants and/or a legally acceptable representative/parent/legal guardian are willing and able to comply with all scheduled visits, vaccination plan, and other study procedures including completion of the e-diary for 7 days for participants after each of 3 vaccinations.
• Participants and/or a legally acceptable representative/parent/legal guardian must be able to be contacted by telephone during study participation.
• Participants and/or a legally acceptable representative/parent/legal guardian are capable of giving signed informed consent.

Exclusion Criteria:

• Major known congenital malformation or serious chronic disorder.
• Known history of TBEV infection.
• Known history of other flavivirus infection (eg, dengue fever, yellow fever, JEV, West Nile virus).
• Known history of infection with HIV, HCV, or HBV.
• Immunocompromised participants with known or suspected immunodeficiency.
• History of autoimmune disease or an active autoimmune disease requiring therapeutic intervention.
• Previous vaccination with any licensed or investigational TBE vaccine, or planned receipt of other flavivirus vaccines apart from JEV vaccine (eg, yellow fever, dengue fever) during the study. Administration of JEV vaccine is prohibited during participation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ≥16 Years Old; TBE vaccine 0.5 mL (intramuscular injection).	Biological: TBE vaccine 0.5 mL; TBE vaccine 0.5 mL (intramuscular injection).
Experimental: 1 to <16 Years Old; TBE vaccine 0.25ｍL (intramuscular injection).	Biological: TBE vaccine 0.25 mL; TBE vaccine 0.25 mL (intramuscular injection).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Seropositive Participants at 4 Weeks After Dose 3	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.	4 weeks after Dose 3
Percentage of Participants With Local Reactions (LR) Within 7 Days After Dose 1	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.	Within 7 days after Dose 1
Percentage of Participants With Local Reactions Within 7 Days After Dose 2	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.	Within 7 days after Dose 2
Percentage of Participants With Local Reactions Within 7 Days After Dose 3	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.	Within 7 days after Dose 3
Percentage of Participants With Systemic Events (SE) Within 7 Days After Dose 1	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).	Within 7 days after Dose 1
Percentage of Participants With Systemic Events 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).	Within 7 days after Dose 2
Percentage of Participants With Systemic Events 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).	Within 7 days after Dose 3
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Dose 1	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.	Within 1 month after Dose 1
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Dose 2	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.	Within 1 month after Dose 2
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Dose 3	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.	Within 1 month after Dose 3
Percentage of Participants With Adverse Events (AEs) Within 1 Month After Any Dose	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.	Within 1 month after any Dose
Percentage of Participants With Serious Adverse Events (SAEs) Throughout the Study	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.	From Day 1 up to end of study (up to approximately 13 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Seropositive Participants at 4 Weeks After Dose 2	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.	4 weeks after Dose 2
Geometric Mean Titers (GMTs) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 2 and Dose 3	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.	4 weeks after Dose 2 and Dose 3
Geometric Mean Fold Rise (GMFR) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 2 as Compared to Baseline	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.	From Baseline to 4 weeks after Dose 2
Geometric Mean Fold Rise (GMFR) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 3 as Compared to Baseline	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.	From Baseline to 4 weeks 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	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.	From 4 weeks after Dose 2 to 4 weeks after Dose 3
Percentage of Participants With Neutralizing Antibody Titers >= Lower Limit of Quantification (LLOQ)	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.	Before Dose 1, 4 weeks after Dose 2, Before Dose 3 and 4 weeks after Dose 3

Collaborators and Investigators

• Sponsor: Pfizer
• Investigators: Study Director: Pfizer CT.gov Call Center, Pfizer

Publications and helpful links

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2021
• Primary Completion (Actual): February 21, 2022
• Study Completion (Actual): February 21, 2022

Study Registration Dates

• First Submitted: November 9, 2020
• First Submitted That Met QC Criteria: November 23, 2020
• First Posted (Actual): December 1, 2020

Study Record Updates

• Last Update Posted (Actual): November 22, 2023
• Last Update Submitted That Met QC Criteria: February 15, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; RNA Virus Infections; Virus Diseases; Infections; Encephalitis, Arbovirus; Encephalitis, Viral; Central Nervous System Viral Diseases; Central Nervous System Infections; Infectious Encephalitis; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Flaviviridae Infections; Tick-Borne Diseases; Neuroinflammatory Diseases; Encephalitis; Encephalitis, Tick-Borne; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: B9371039

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No