Clinical Trial Results:
A phase III, open-label, single-group, multi-centre study to assess the immunogenicity, safety and
reactogenicity of GSK Biologicals’ combined reduced antigen content diphtheria, tetanus and acellular pertussis (dTpa) vaccine, Boostrix, administered as a booster dose in healthy Russian subjects aged four years and older.
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Summary
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EudraCT number |
2015-003405-42 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
31 Aug 2018
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Results information
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Results version number |
v1(current) |
This version publication date |
21 Sep 2019
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First version publication date |
21 Sep 2019
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Other versions |
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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 |
201532
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03311659 | ||
WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
GlaxoSmithKline Biologicals
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Sponsor organisation address |
Rue de l'Institut 89, Rixensart, Belgium, B-1330
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Public contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.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 |
10 Mar 2019
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 Aug 2018
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Global end of trial reached? |
Yes
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Global end of trial date |
31 Aug 2018
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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 assess the immune response to the dTpa vaccine in terms of seroprotection status
for antibodies against diphtheria and tetanus antigens and in terms of seropositivity
status for antibodies against the pertussis antigens [pertussis toxoid (PT), filamentous
haemagglutinin (FHA) and pertactin (PRN)], one month after vaccination.
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Protection of trial subjects |
Appropriate medical treatment was readily available in case of anaphylactic reactions following the administration of the vaccine. For this reason, the vaccinee remained under medical supervision for 30 minutes after vaccination.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
26 Jan 2018
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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 |
Russian Federation: 447
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Worldwide total number of subjects |
447
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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) |
0
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Children (2-11 years) |
130
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Adolescents (12-17 years) |
92
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Adults (18-64 years) |
113
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From 65 to 84 years |
101
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85 years and over |
11
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Recruitment
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Recruitment details |
- | ||||||||||
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Pre-assignment
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Screening details |
Out of 448 enrolled subjects, only 447 were vaccinated. One subject was withdrawn prior to vaccination. | ||||||||||
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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 |
Non-randomised - controlled
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Blinding used |
Not blinded | ||||||||||
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Arms
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Arm title
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dTpa group | ||||||||||
Arm description |
Healthy female and male subjects with age 4 years and above and who received a single dose of Boostrix vaccine at Day 1. | ||||||||||
Arm type |
Other | ||||||||||
Investigational medicinal product name |
Boostrix
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Investigational medicinal product code |
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Other name |
SB263855
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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 |
1 dose at Day 1
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Baseline characteristics reporting groups
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Reporting group title |
dTpa group
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Reporting group description |
Healthy female and male subjects with age 4 years and above and who received a single dose of Boostrix vaccine at Day 1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
dTpa group
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Reporting group description |
Healthy female and male subjects with age 4 years and above and who received a single dose of Boostrix vaccine at Day 1. | ||
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End point title |
Number of seroprotected subjects for anti-diphtheria (anti-D) [1] | ||||||||||
End point description |
A seroprotected subject was a subject whose anti-D concentrations are greater than or equal to (≥) 0.1 International units per milliliter (IU/ml). Seroprotection was assessed by enzyme-linked immunosorbent assay (ELISA) method. In addition, sera with ELISA concentrations <0.1 IU/ml were tested for neutralising antibodies using a Vero-cell neutralisation assay. Both the ELISA test (antibody concentrations ≥ 0.1 IU/ml) and Vero-cell test (antibody concentration ≥ 0.01 IU/ml) defined the seroprotection status for the primary endpoint.
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End point type |
Primary
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End point timeframe |
At Day 31
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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: This endpoint was descriptive, hence no statistical analyses were available. |
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| No statistical analyses for this end point | |||||||||||
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End point title |
Number of seroprotected subjects for anti-tetanus (anti-T) [2] | ||||||||
End point description |
A seroprotected subject was a subject whose anti-T concentrations are greater than or equal to (≥) 0.1 International units per milliliter (IU/ml). Seroprotection was assessed by enzyme-linked immunosorbent assay (ELISA) method.
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End point type |
Primary
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End point timeframe |
At Day 31
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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: This endpoint was descriptive, hence no statistical analyses were available. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Number of seropositive subjects for anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) [3] | ||||||||||||
End point description |
A seropositive subject was a subject whose antibody concentration was greater than or equal to the assay cut-off value. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA and 2.187 IU/mL for anti-PRN respectively.
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End point type |
Primary
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End point timeframe |
At Day 31
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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: This endpoint was descriptive, hence no statistical analyses were available. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects with a booster response to diphtheria and tetanus antigens, one month after vaccination | ||||||||||||||||||
End point description |
Booster response to diphtheria (D) and tetanus (T) antigens was defined as: for subjects with pre-vaccination antibody concentration <0.1 IU/ml (i.e. below the seroprotection cut-off), antibody concentrations at least ≥0.4 IU/ml, one month after vaccination, and for subjects with pre-vaccination antibody concentration ≥0.1 IU/ml (i.e. equal or above the seroprotection cut-off), an increase in antibody concentrations of at least four times the pre-vaccination concentration, one month after vaccination. Seronegative (S-) subjects are those who have antibody concentration less than (<) 0.1 IU/mL and seropositive (S+) subjects are those who have antibody concentration ≥ 0.1 IU/mL prior to vaccination.
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End point type |
Secondary
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End point timeframe |
At Day 31
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of subjects with a booster response to the PT, FHA and PRN antigens, one month after vaccination | ||||||||||||||||||||||||||||||
End point description |
Booster response to PT, FHA and PRN antigens was defined as: for subjects with pre-vaccination antibody concentration below (<) the assay cut-off, post-vaccination antibody concentration ≥ 4 times the assay cut-off; for subjects with pre-vaccination antibody concentration between the assay cut-off and <4 times the assay cut-off, post-vaccination antibody concentration ≥ 4 times the pre-vaccination antibody concentration; and for subjects with pre-vaccination antibody concentration ≥ 4 times the assay cut-off, post-vaccination antibody concentration ≥ 2 times the pre-vaccination antibody concentration. Seronegative (S-) subjects are those who have antibody concentration less than (<) assay cut-off and seropositive (S+) subjects are those who have antibody concentration ≥ assay cut-off prior to vaccination. Assay cut-off was 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA and 2.187 IU/mL for anti-PRN respectively.
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End point type |
Secondary
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End point timeframe |
At Day 31
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| No statistical analyses for this end point | |||||||||||||||||||||||||||||||
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End point title |
Anti-D, anti-T, anti-PT, anti-FHA and anti-PRN antibody concentrations, one month after vaccination | ||||||||||||||||||
End point description |
Antibody concentrations are presented as Geometric Mean Concentrations (GMCs) and expressed in International Units per milliliter (IU/mL). The cut-off for the assays were: 0.057 IU/mL for anti-D, 0.043 IU/mL for anti-T, 2.693 IU/mL for anti-PT, 2.046 IU/mL for anti-FHA and 2.187 IU/mL for anti-PRN, respectively.
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End point type |
Secondary
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End point timeframe |
At Day 31
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Number of subjects with solicited local symptoms | ||||||||||||
End point description |
Assessed solicited local symptoms were pain, redness, swelling. Any = Occurrence of any local symptom regardless of its intensity grade. Any redness and swelling were defined as greater than (>) 0 millimeters (mm) diameter for all subjects.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Day 1–4) follow-up period after vaccination.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects aged below 6 years with solicited general symptoms | ||||||||||||||
End point description |
Assessed solicited general symptoms were Drowsiness, Irritability/Fussiness, Loss of appetite and Fever. Any = Occurrence of any general symptom regardless of its intensity grade and relationship to the study vaccination. Fever was defined as temperature ≥38.0 degrees Celsius (°C). The location for measuring temperature was the axilla.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Day 1–4) follow-up period after vaccination.
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of subjects aged above and equal to 6 years with solicited general symptoms | ||||||||||||||
End point description |
Assessed solicited general symptoms were Fatigue, Gastrointestinal symptoms (included nausea, vomiting, diarrhoea and/or abdominal pain), Headache and Fever. Any = Occurence of any general symptom regardless of its intensity grade and relationship to the study vaccination. Fever was defined as axilla temperature ≥ 38 degrees Celsius (°C).
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End point type |
Secondary
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End point timeframe |
During the 4-day (Day 1–4) follow-up period after vaccination.
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| No statistical analyses for this end point | |||||||||||||||
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End point title |
Number of subjects with large swelling reactions | ||||||
End point description |
Large injection site reaction for subjects <6 years of age defined as a swelling with a diameter of >50 mm and for subjects >=6 years of age swelling with a diameter of >100 mm, noticeable diffuse swelling or noticeable increase in limb circumference. Any = Occurence of any large swelling regardless of its intensity grade and relationship to the study vaccination.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Day 1–4) follow-up period after vaccination.
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| No statistical analyses for this end point | |||||||
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End point title |
Number of subjects with unsolicited adverse events (AEs) | ||||||
End point description |
Any unsolicited AE was defined as any AE reported in addition to those solicited during the clinical study. Also any ‘solicited’ symptom with onset outside the specified period of follow-up for solicited symptoms will be reported as an unsolicited adverse event.
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End point type |
Secondary
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End point timeframe |
During the 31-day (Day 1–31) follow-up period after vaccination
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| No statistical analyses for this end point | |||||||
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End point title |
Number of subjects with serious adverse events (SAEs) | ||||||
End point description |
A SAE is any untoward medical occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in disability/incapacity or is a congenital anomaly/birth defect in the offspring of a study subject.
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End point type |
Secondary
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End point timeframe |
From Day 1 to Day 31
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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 |
Unsolicited adverse events (AEs) during the 31-day follow-up period after vaccination. Serious adverse events were reported during the whole study period (from Day 1 up to study conclusion at Day 31).
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Adverse event reporting additional description |
Solicited adverse events were not reported in this section. They were defined for both age strata (subjects less than 6 years and subjects equal or greater than 6 years), and then, analyzed per age stratum. Please refer to the outcomes section for the results.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
21.0
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Reporting groups
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Reporting group title |
dTpa group
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Reporting group description |
Healthy female and male subjects with age 4 years and above and who received a single dose of Boostrix vaccine at Day 1. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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02 Feb 2017 |
The protocol has been amended to implement the following changes:
• The age at inclusion to study has been changed from 3 to 4 years of age in order to be in compliant with Boostrix’s approved EU label wherein it is indicated for booster vaccination in individuals aged four years and older.
• Wording “parents/Legally Acceptable Representative(s) (LAR[s])” is replaced by the wording “parents/adoptive parents”. As per Russian legislation, only parents or adoptive parents can give consent for the enrolment of their child in a clinical trial. No other person is allowed to give consent on behalf of a minor to participate in a clinical trial.
• The age groups are amended according to the approved Boostrix EU label and physiological particularities i.e, from 3-9 to 4-9 years (children), 10-19 to 10-17 years (adolescents), 20-64 to 18-64 years (adults) and ≥ 65 years (elderly population).
• To reflect the upgrade to new version for protocol (15.0), ICF (8.0), eCRF, SPM and overall changes in the functions.
• The inclusion criteria has been amended in order to clarify the following,
- Children from four to seven years of age who have received diphtheria, tetanus and pertussis vaccination prior to study enrolment as per local recommendations will be enrolled
- Subjects eight years of age and older who have received diphtheria, tetanus and pertussis vaccination to the best of their/subjects’ parent(s)/subjects’ adoptive parent(s) knowledge and did not receive an additional diphtheria, tetanus or pertussis vaccination within 5 years prior to enrolment in the study will be enrolled. |
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07 Aug 2017 |
This protocol amendment was developed after the comments from the Russian regulatory authorities [Ministry of Health (MoH)]. Adjustments to the text were made in certain sections for better readability and to clarify the inclusion and exclusion criteria for enrolment of subjects and the conduct of the study. In addition, adjustments for the reporting period and assessment of adverse events in the safety sections were made for consistency. Typos and errors were corrected throughout the document. The newly re-developed and re-validated GSK’s DTPa ELISA cut-offs were updated as per the most recent CBER recommendation (2017). |
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31 Oct 2017 |
This protocol amendment was developed in order to accommodate older adults (approximately 58 years old and older) who were born before national recommendations in Russia for infant DTP vaccination, as well as those born when DTP vaccination coverage was low. The protocol amendment would also clarify inconsistencies present in the Protocol Amendment 2, between the English version and the Russian version. Following which, adjustments to the text were made in the inclusion criteria to clarify the enrolment of subjects for age group eight years and above. The wording parent(s)/adoptive parent(s) were aligned according to the local regulations. References for laboratory assays were updated and certain sections were modified to align with the rest of the document. |
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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 | |||
