Clinical Trial Results:
A single blind, randomized comparative and multicentre clinical trial of the immunogenicity and safety of booster immunisation with tetanus monovalent vaccines VACTETA 40 IU/0,5 ml (BIODRUG) and TETAVAX (Sanofi Pasteur SA) in healthy adults.
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Summary
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EudraCT number |
2016-004934-11 |
Trial protocol |
CZ |
Global end of trial date |
29 May 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
19 Aug 2017
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First version publication date |
19 Aug 2017
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Other versions |
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Summary report(s) |
Study report synopsis TeVaTri042017 v1.3 |
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 |
TeVaTri042017
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
BIODRUG s.r.o.
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Sponsor organisation address |
Boženy Němcovej 8, Bratislava, Slovakia, 811 04
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Public contact |
Clinical Trial Information Desk, RECLINMED s.r.o., +420 608 881 826, info@reclinmed.cz
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Scientific contact |
Clinical Trial Information Desk, RECLINMED s.r.o., +420 608 881 826, info@reclinmed.cz
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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? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Jun 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
29 May 2017
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Global end of trial reached? |
Yes
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Global end of trial date |
29 May 2017
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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 |
Evaluation of immunogenicity of tetanus monovalent vaccine Vacteta after booster immunisation of health adults compared with that induced by vaccine Tetavax.
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Protection of trial subjects |
The risk to subjects enrolled in this study is not higher than the general risks of adverse reactions after tetanus vaccination because both commercial vaccines are registered in the Czech Republic. Subjects will not be exposed to more stress or pain than they are from the vaccination or blood sampling.
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Background therapy |
Healthy adults | ||
Evidence for comparator |
The control vaccine, further called as reference vaccine, was chosen as it is the only one monovalent vaccine against tetanus available and authorised in the Czech Republic. There was no other reason of this selection. | ||
Actual start date of recruitment |
28 Mar 2017
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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 |
Czech Republic: 200
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Worldwide total number of subjects |
200
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EEA total number of subjects |
200
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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) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
200
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
In the study was planned to enrol a total of 200 subjects recruited from healthy adults. All patients were selected from outpatient’s clinic (clinical sites) according to inclusion and exclusion criteria. In one clinical site, there were planned to enrol a total of 50 subjects. | |||||||||
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Pre-assignment
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Screening details |
Subjects must have written confirmation on previous immunisation against tetanus not later than 15.9 years and not early than 9.9 years | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Single blind | |||||||||
Roles blinded |
Subject | |||||||||
Blinding implementation details |
The single blinding was achieved by simple overlapping of subject eyes with a mask before the administration of vaccine. So a subject did not know which vaccine had been administered to him. The single blinding helped especially to objectively assess any adverse events.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Test medication | |||||||||
Arm description |
Subjects received one dose of test vaccine Vacteta. | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Vacteta 40 IU/0.5 ml
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Investigational medicinal product code |
SUB12609MIG
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Other name |
TETANUS TOXOID ADSORBED
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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 |
The vaccine was administered intramuscularly to minimize the occurrence of local adverse reactions as it is recommended by the manufacture. The recommended site of the application was deltoid region in adults.
The vaccine dose was the same for both vaccines, i.e. volume of 0.5 ml. The concentration of dose was also identical for both vaccines, i.e. at least 40 IU/0.5 ml. The volume of dose, including the way of administration was in accordance of SmPC of both study vaccines.
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Arm title
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Reference medication | |||||||||
Arm description |
Subjects received one dose of reference vaccine Tetavax. | |||||||||
Arm type |
Active comparator | |||||||||
Investigational medicinal product name |
Tetavax
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Investigational medicinal product code |
SUB12609MIG
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Other name |
TETANUS TOXOID ADSORBED
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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 |
The vaccine was administered intramuscularly to minimize the occurrence of local adverse reactions as it is recommended by the manufacture. The recommended site of the application was deltoid region in adults.
The vaccine dose was the same for both vaccines, i.e. volume of 0.5 ml. The concentration of dose was also identical for both vaccines, i.e. at least 40 IU/0.5 ml. The volume of dose, including the way of administration was in accordance of SmPC of both study vaccines.
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Baseline characteristics reporting groups
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Reporting group title |
Test medication
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Reporting group description |
Subjects received one dose of test vaccine Vacteta. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Reference medication
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Reporting group description |
Subjects received one dose of reference vaccine Tetavax. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
ITT
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The primary objective of proving non-inferiority based on primary analysis of variables performed on the ITT set (intention-to-treat) subjects is conservative in approach. This set included all subjects since each subject had the primary endpoint, i.e. the concentration of tetanus-specific antibodies at the started and completed milestone.
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End points reporting groups
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Reporting group title |
Test medication
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Reporting group description |
Subjects received one dose of test vaccine Vacteta. | ||
Reporting group title |
Reference medication
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Reporting group description |
Subjects received one dose of reference vaccine Tetavax. | ||
Subject analysis set title |
ITT
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
The primary objective of proving non-inferiority based on primary analysis of variables performed on the ITT set (intention-to-treat) subjects is conservative in approach. This set included all subjects since each subject had the primary endpoint, i.e. the concentration of tetanus-specific antibodies at the started and completed milestone.
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End point title |
seroconversion rate | |||||||||
End point description |
The seroconversion rate was evaluated positive if the increase in antibody levels is at least 4-fold. If the tetanus-specific antibody concentrations prior to administering the booster dose was equal to or less than 0.1 IU/ml, then the seroconversion rate was positive when the post-vaccination concentration was at least 4-fold higher than the pre-vaccination concentration and the post-vaccination concentration was at least 0.4 IU/ml.
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End point type |
Primary
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End point timeframe |
Between started and completed milestone
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Statistical analysis title |
difference between test and reference vaccine | |||||||||
Statistical analysis description |
Fisher’s exact test; asymptotic interval
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Comparison groups |
Test medication v Reference medication
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Number of subjects included in analysis |
200
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [1] | |||||||||
P-value |
< 0.05 [2] | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
3
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-9.76 | |||||||||
upper limit |
15.8 | |||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
6.51
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| Notes [1] - The efficacy objective was met if the seroconversion rate induced with Vacteta vaccine was not worse than 10% compared to reference vaccine-induced seroconversion rate (i.e. seroconversion rates of test minus reference vaccine, including the lower limit of the 95% confidence interval of this difference was not lower than -10%). [2] - The significance level was determined 0.05 for the test of null hypothesis of non-inferiority at a two-sided 95% confidence interval because this study was designed to be non-inferior based on the substantial similarity of both tetanus vaccines. |
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End point title |
geometric mean of antibodies specific against tetanus | ||||||||||||
End point description |
A secondary objective is to confirm not a worse immune response demonstrated with the 95% confidence interval of geometric mean of tetanus-specific antibody concentrations after booster immunisation with the test vaccine compared to that of the reference one.
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End point type |
Secondary
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End point timeframe |
completed milestone
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Statistical analysis title |
ratio of geometric means - test/reference | ||||||||||||
Statistical analysis description |
It was computed as a difference of logarithms of both geometric means. It was reasonable to assume that two populations (antibody concentrations) have the same standard deviation, therefore a procedure known as the pooled t procedure could be.
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Comparison groups |
Test medication v Reference medication
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Number of subjects included in analysis |
200
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority [3] | ||||||||||||
Method |
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Parameter type |
ratio | ||||||||||||
Point estimate |
0.88
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Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
0.76 | ||||||||||||
upper limit |
1.02 | ||||||||||||
Variability estimate |
Standard error of the mean
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Dispersion value |
0.224
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| Notes [3] - If the lower limit of this ratio interval (i.e. anti-T [Vacteta] / anti-T [Tetavax]) is ≥0.5 and the two-sided confidence interval will contain 1, then the criterion of non-inferiority will be met. |
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Adverse events information
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Timeframe for reporting adverse events |
started and completed milestone
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Adverse event reporting additional description |
The measures of safety used in this study were routine clinical procedures. They were chosen to capture known undesirable effects of tetanus vaccination from the SmPC. Safety measures were conducted by the investigators. They included close vigilance for reporting of reactions on the day of immunisation and 4 weeks after immunisation
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Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
20
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Reporting groups
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Reporting group title |
test vaccine
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Reporting group description |
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Reporting group title |
reference vaccine
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Reporting group description |
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| Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
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. | |||
| Not applicable. | |||
