Clinical Trial Results:
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
Summary
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EudraCT number |
2022-004181-37 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
21 Feb 2022
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Results information
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Results version number |
v1(current) |
This version publication date |
03 Mar 2023
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First version publication date |
03 Mar 2023
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Other versions |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
B9371039
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04648241 | ||
WHO universal trial number (UTN) |
- | ||
Sponsors
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Sponsor organisation name |
Pfizer Inc.
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Sponsor organisation address |
235 E 42nd Street, New York, United States, 10017
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Public contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Scientific contact |
Pfizer ClinicalTrials.gov Call Center, Pfizer Inc., 001 18007181021, ClinicalTrials.gov_Inquiries@pfizer.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
Yes
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
17 Oct 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Feb 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the immunogenicity of Tick-borne Encephalitis (TBE) vaccine 0.5 mL and 0.25 mL by NT
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Protection of trial subjects |
The study was in compliance with the ethical principles derived from the Declaration of Helsinki and in compliance with all International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines. All the local regulatory requirements pertinent to safety of trial subjects were followed.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
18 Jan 2021
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Japan: 165
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Worldwide total number of subjects |
165
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
2
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Children (2-11 years) |
52
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Adolescents (12-17 years) |
16
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Adults (18-64 years) |
80
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From 65 to 84 years |
15
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85 years and over |
0
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Recruitment
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Recruitment details |
This study was conducted as part of the Phase 3 clinical development plan to support the use of TBE vaccine 0.5 milliliter (mL) in healthy Japanese adults (greater than or equal to [>=] 16 years old) and 0.25 mL in pediatric subjects (>=1 and less than [<] 16 years old) at investigator sites in Japan. | |||||||||||||||
Pre-assignment
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Screening details |
The study was conducted in single country from 18 January 2021 to 21 February 2022. A total of 165 subjects were enrolled. | |||||||||||||||
Period 1
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Period 1 title |
Overall Study (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Adults (>=16 years old) | |||||||||||||||
Arm description |
Subjects 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. Subjects were followed up for safety for 21-35 days after Dose 3. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Tick-borne encephalitis vaccine
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Investigational medicinal product code |
PF-06830414
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Subjects received three doses of 0.5 mL TBE vaccine intramuscularly.
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Arm title
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Pediatric (1 to <16 Years Old) | |||||||||||||||
Arm description |
Subjects 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. Subjects were followed up for safety for 21-35 days after Dose 3. | |||||||||||||||
Arm type |
Experimental | |||||||||||||||
Investigational medicinal product name |
Tick-borne encephalitis vaccine
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Investigational medicinal product code |
PF-06830414
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Other name |
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Pharmaceutical forms |
Suspension for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
Subjects received three doses of 0.25 mL TBE vaccine intramuscularly.
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Baseline characteristics reporting groups
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Reporting group title |
Adults (>=16 years old)
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Reporting group description |
Subjects 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. Subjects were followed up for safety for 21-35 days after Dose 3. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pediatric (1 to <16 Years Old)
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Reporting group description |
Subjects 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. Subjects were followed up for safety for 21-35 days after Dose 3. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Adults (>=16 years old)
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Reporting group description |
Subjects 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. Subjects were followed up for safety for 21-35 days after Dose 3. | ||
Reporting group title |
Pediatric (1 to <16 Years Old)
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Reporting group description |
Subjects 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. Subjects were followed up for safety for 21-35 days after Dose 3. | ||
Subject analysis set title |
Pediatric (3 to 15 Years Old)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects aged 3 to 15 years old received three doses of 0.25 mL TBE vaccine intramuscularly as Dose 1 on Day 1, Dose 2 in between 21 to 35 days after Dose 1 and Dose 3 between 150-365 days after Dose 2. Subjects were followed up for safety for 21-35 days after Dose 3.
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Subject analysis set title |
Pediatric (1 to 2 Years Old)
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
Subjects aged 1 to 2 years 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 in between 150-365 days after Dose 2. Subjects were followed up for safety for 21-35 days after Dose 3.
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End point title |
Percentage of Seropositive Subjects at 4 Weeks After Dose 3 [1] | ||||||||||||
End point description |
Seropositivity rate based on the immune response was determined by neutralization test (NT). Subjects who achieved tick-borne encephalitis virus (TBEV) NT titers greater than or equal to (>=) 1:10 were considered as seropositive. Exact 2-sided 95% confidence interval (CI) based on the Clopper and Pearson method was presented. Evaluable immunogenicity (EI) population: Subjects who received all 3 doses of the investigational product(IP), 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. Number of subjects analysed=subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
4 weeks after Dose 3
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Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Local Reactions (LR) Within 7 Days After Dose 1 [2] | |||||||||||||||||||||||||||||||||||||||
End point description |
LR:subject or legally acceptable representative/parent/legal guardian using an electronic diary (e-diary).LR:redness, swelling & pain at injection site.Redness & swelling measured using measuring device units.1 measuring device unit=0.5 centimeter(cm).Redness & swelling were graded as: for subjects >=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 subjects 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 injection site was graded as: for subjects >2 years of age, mild(does not interfere with activity),moderate(interferes with activity) and severe(prevents daily activity); for subjects 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). Safety analysis included all enrolled subjects who received at least 1 dose of IP.
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End point type |
Primary
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End point timeframe |
Within 7 days after Dose 1
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Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Local Reactions Within 7 Days After Dose 2 [3] | |||||||||||||||||||||||||||||||||||||||
End point description |
LR:subject 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 subjects >=12 years of age, mild (>2.0 to 5.0 cm), moderate(>5.0 to 10.0 cm) and severe (>10.0 cm); for subjects <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 subjects >2 years of age, mild(does not interfere with activity), moderate(interferes with activity) and severe(prevents daily activity); for subjects <=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. Safety set analysed.
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End point type |
Primary
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End point timeframe |
Within 7 days after Dose 2
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Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Local Reactions Within 7 Days After Dose 3 [4] | |||||||||||||||||||||||||||||||||||||||
End point description |
LR:subject 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 subjects >=12 years of age, mild (>2.0 to 5.0 cm), moderate(>5.0 to 10.0 cm) and severe (>10.0 cm); for subjects <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 subjects >2 years of age, mild(does not interfere with activity), moderate(interferes with activity) and severe(prevents daily activity); for subjects <=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. Safety set analyzed.
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End point type |
Primary
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End point timeframe |
Within 7 days after Dose 3
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Notes [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Systemic Events (SE) Within 7 Days After Dose 1 [5] [6] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
SE:subjects/legally acceptable representative/parent/legal guardian using e-diary,fever:temperature >=37.5 degree(deg)Celsius (C),categorized:37.5to38.4, 38.5to38.9, 39.0to40.0, >40.0degC.Fatigue, headache, muscle pain, joint pain: mild(didn’t interfere with activity),moderate(mod)(some interference with activity),severe(prevented daily activity).Vomiting: mild(1-2 times in 24 hours[hrs]),mod(>2 times in 24hrs),severe(required IV hydration).Diarrhea: mild(2-3 loose stools in 24hrs),mod(4-5 loose stools in 24hrs), severe(6 or more loose stools in 24hrs). Decreased appetite: mild(decreased interest in eating), mod(decreased oral intake), severe(refusal to feed).Drowsiness: mild(Increased sleeping bouts), mod(slightly subdued interfering with daily activity), severe(disabling not interested in usual daily activity). Irritability: mild(easily consolable),mod(required increased attention), severe(inconsolable).Safety set . 99999=not applicable.n=subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Within 7 days after Dose 1
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Notes [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. [6] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Systemic Events Within 7 Days After Dose 2 [7] [8] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
SE: subjects/legally acceptable representative/parent/legal guardian using e-diary. It included fever: temperature >=37.5 deg C and categorised as 37.5 to 38.4, 38.5 to 38.9, 39.0 to 40.0, >40.0 deg C. Fatigue, headache, muscle pain, joint pain: mild(didn’t interfere with activity),mod(some interference with activity),severe(prevented daily activity). Vomiting: mild(1-2 times in 24 hours[hrs]),mod(>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) .Safety set .99999=not applicable.n=subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Within 7 days after Dose 2
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Notes [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. [8] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: The endpoint was planned to be analyzed for Overall Study Adults (>=16 years old), Pediatric (3 to 15 Years Old) and Pediatric (1 to 2 Years Old) arms. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Systemic Events Within 7 Days After Dose 3 [9] [10] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
SE: subjects/legally acceptable representative/parent/legal guardian using e-diary. It included fever: temperature >=37.5 deg C and categorised as 37.5 to 38.4, 38.5 to 38.9, 39.0 to 40.0, >40.0 deg C. Fatigue, headache, muscle pain, joint pain: mild(didn’t interfere with activity),mod(some interference with activity),severe(prevented daily activity). Vomiting: mild(1-2 times in 24 hours[hrs]),mod(>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) .Safety set .99999=not applicable.n=subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Within 7 days after Dose 3
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Notes [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Adverse Events (AEs) Within 1 Month After Dose 1 [11] | ||||||||||||
End point description |
An AE was defined as any untoward medical occurrence in a clinical study subject, 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. Safety analysis population included all enrolled subjects who received at least 1 dose of the investigational product.
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End point type |
Primary
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End point timeframe |
Within 1 month after Dose 1
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Notes [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Adverse Events (AEs) Within 1 Month After Dose 2 [12] | ||||||||||||
End point description |
An AE was defined as any untoward medical occurrence in a clinical study subject, 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. Safety analysis population included all enrolled subjects who received at least 1 dose of the investigational product. Number of subjects analysed= subjects evaluable for this endpoint.
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End point type |
Primary
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End point timeframe |
Within 1 month after Dose 2
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Notes [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The endpoint was planned to be analyzed for Overall Study Adults (>=16 years old), Pediatric (3 to 15 Years Old) and Pediatric (1 to 2 Years Old) arms. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Adverse Events (AEs) Within 1 Month After any Dose [13] | ||||||||||||
End point description |
An AE was defined as any untoward medical occurrence in a clinical study subject, 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. Safety analysis population included all enrolled subjects who received at least 1 dose of the investigational product.
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End point type |
Primary
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End point timeframe |
Within 1 month after any Dose
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Notes [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Adverse Events (AEs) Within 1 Month After Dose 3 [14] | ||||||||||||
End point description |
An AE was defined as any untoward medical occurrence in a clinical study subject, 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. Safety analysis population included all enrolled subjects who received at least 1 dose of the investigational product.
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End point type |
Primary
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End point timeframe |
Within 1 month after Dose 3
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Notes [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The endpoint was planned to be analyzed for Overall Study Adults (>=16 years old), Pediatric (3 to 15 Years Old) and Pediatric (1 to 2 Years Old) arms. |
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects With Serious Adverse Events (SAEs) Throughout the Study [15] | ||||||||||||
End point description |
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 subjects with SAEs and the exact 2-sided 95% CI based on the Clopper and Pearson method was presented. Safety analysis population included all enrolled subjects who received at least 1 dose of the investigational product.
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End point type |
Primary
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End point timeframe |
From Day 1 up to 35 days after Dose 3 (up to approximately 15 months)
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Notes [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Only descriptive data was planned to be analyzed for this endpoint. |
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No statistical analyses for this end point |
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End point title |
Percentage of Seropositive Subjects at 4 Weeks After Dose 2 | ||||||||||||
End point description |
Seropositivity rate based on the immune response was determined by NT. Subjects 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. Evaluable immunogenicity population for the second dose: Subjects 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.
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End point type |
Secondary
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End point timeframe |
4 weeks after Dose 2
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No statistical analyses for this end point |
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End point title |
Geometric Mean Titers (GMTs) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 2 and Dose 3 | ||||||||||||||||||
End point description |
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. EI population: Subjects 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. Here, “Number of Subjects Analysed” signifies subjects who were evaluable for this end point.
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End point type |
Secondary
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End point timeframe |
4 weeks after Dose 2 and Dose 3
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No statistical analyses for this end point |
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End point title |
Geometric Mean Fold Rise (GMFR) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 2 as Compared to Baseline | ||||||||||||
End point description |
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. Evaluable immunogenicity population for the second dose: Subjects 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.
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End point type |
Secondary
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End point timeframe |
From Baseline to 4 weeks after Dose 2
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No statistical analyses for this end point |
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End point title |
Geometric Mean Fold Rise (GMFR) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 3 as Compared to Baseline | ||||||||||||
End point description |
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. EI population: Subjects 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. Here, “Number of subjects analysed” signifies subjects who were evaluable for this endpoint.
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End point type |
Secondary
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End point timeframe |
From Baseline to 4 weeks after Dose 3
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No statistical analyses for this end point |
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End point title |
Geometric Mean Fold Rise (GMFR) of TBEV Neutralizing Antibody Titers at 4 Weeks After Dose 3 as Compared to 4 Weeks After Dose 2 | ||||||||||||
End point description |
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. EI population: Subjects 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. Here, “Number of subjects analysed” signifies subjects who were evaluable for this endpoint.
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End point type |
Secondary
|
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End point timeframe |
From 4 weeks after Dose 2 to 4 weeks after Dose 3
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|
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No statistical analyses for this end point |
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End point title |
Percentage of Subjects with Neutralizing Antibody Titers >= Lower Limit of Quantification (LLOQ) | ||||||||||||||||||||||||
End point description |
The LLOQ value for NT was 5. Assay results below the LLOQ were set to 0.5 × LLOQ. Percentage of subjects with NT>=LLOQ and exact 2-sided 95% CI based on the Clopper and Pearson method was presented. EI population: Subjects 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. Here, “Number of subjects analysed” signifies subjects who were evaluable for this endpoint.
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End point type |
Secondary
|
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End point timeframe |
Before Dose 1, 4 weeks after Dose 2, Before Dose 3 and 4 weeks after Dose 3
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No statistical analyses for this end point |
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Adverse events information
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Timeframe for reporting adverse events |
All-Cause mortality: from Day(D)1 up to 35D after Dose3(up to approximately 15months([M]); SAEs:from D1 up to 35D after Dose3(up to approx.15M);Other AEs(non-systematic assessment[SA]):up to 1M after each Dose;LR&SE(SA,other AEs):within 7Dafter each Dose)
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Adverse event reporting additional description |
Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorised as serious in one subject and as non-serious in another, or a subject may have experienced both a serious and non-serious event.
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Assessment type |
Non-systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
v 24.1
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Reporting groups
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Reporting group title |
Adults (>=16 years old)
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Reporting group description |
Subjects 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. Subjects were followed up for safety for 21-35 days after Dose 3. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Pediatric (1 to <16 Years Old)
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Reporting group description |
Subjects 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. Subjects were followed up for safety for 21-35 days after Dose 3. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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10 Nov 2020 |
Added fever to prespecified systemic events in primary safety endpoints for subjects 1 to <=2 years of age. |
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Interruptions (globally) |
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Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
None reported |