Clinical Trial Results:
A randomised, open-label study to assess the immunogenicity and safety of GSK Biologicals’ IPV vaccine administered as a three-dose primary vaccination course at 2-3-4 months of age in healthy infants in China.
Summary
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EudraCT number |
2011-003167-30 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
05 Jul 2010
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Results information
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Results version number |
v3(current) |
This version publication date |
19 Apr 2023
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First version publication date |
01 Jul 2015
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Other versions |
v1 , v2 |
Version creation reason |
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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 |
112679
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01021293 | ||
WHO universal trial number (UTN) |
- | ||
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, 44 2089904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, 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 |
15 Feb 2011
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
05 Jul 2010
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Global end of trial reached? |
Yes
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Global end of trial date |
05 Jul 2010
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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 demonstrate the non-inferiority of GSK Biologicals’ IPV vaccine as compared to the Chinese OPV vaccine in terms of the immune response to poliovirus type 1, 2 and 3, one month after the third vaccine dose.
Non-inferiority in terms of immunogenicity to the three poliovirus antigens will be demonstrated if the upper limit of the 95% confidence interval (CI) on the group difference [Control Group minus Poliorix Group] in the percentage of seroprotected subjects is less than or equal to 10%.
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Protection of trial subjects |
The subjects were observed closely for at least 30 minutes, with appropriate medical treatment readily available in case of anaphylaxis following the administration of vaccines.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
28 Nov 2009
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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 |
China: 1101
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Worldwide total number of subjects |
1101
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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) |
1101
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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) |
0
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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 |
Of the 1101 enrolled subjects, one subject was not randomised and administered any vaccine as the parents of the subject refused to vaccinate their child after blood collection at Visit 1 and withdrew their consent. | |||||||||||||||||||||||||||
Pre-assignment
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Screening details |
During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms. | |||||||||||||||||||||||||||
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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Poliorix Group | |||||||||||||||||||||||||||
Arm description |
Healthy male and female Chinese infants between, and including 60 and 90 days of age, who received 3 doses of Poliorix (IPV) vaccine at 2, 3 and 4 months of age, administered intramuscularly into the anterolateral side of the right thigh. | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Poliorix
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intramuscular use
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Dosage and administration details |
3 doses of IPV vaccine administered intramuscularly into the anterolateral side of the right thigh.
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Arm title
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Control Group | |||||||||||||||||||||||||||
Arm description |
Healthy male and female Chinese infants between, and including 60 and 90 days of age, who received 3 doses of Oral Poliomyelitis Vaccine (OPV) at 2, 3 and 4 months of age, according to the vaccination policy recommended in China. | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
Oral Poliomyelitis Vaccine (OPV)
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
3 doses of OPV vaccine administered orally.
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Notes [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same. Justification: Of the 1101 enrolled subjects, one subject was not randomised and administered any vaccine as the parents of the subject refused to vaccinate their child after blood collection at Visit 1 and withdrew their consent. |
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Baseline characteristics reporting groups
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Reporting group title |
Poliorix Group
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Reporting group description |
Healthy male and female Chinese infants between, and including 60 and 90 days of age, who received 3 doses of Poliorix (IPV) vaccine at 2, 3 and 4 months of age, administered intramuscularly into the anterolateral side of the right thigh. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Control Group
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Reporting group description |
Healthy male and female Chinese infants between, and including 60 and 90 days of age, who received 3 doses of Oral Poliomyelitis Vaccine (OPV) at 2, 3 and 4 months of age, according to the vaccination policy recommended in China. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Poliorix Group
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Reporting group description |
Healthy male and female Chinese infants between, and including 60 and 90 days of age, who received 3 doses of Poliorix (IPV) vaccine at 2, 3 and 4 months of age, administered intramuscularly into the anterolateral side of the right thigh. | ||
Reporting group title |
Control Group
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Reporting group description |
Healthy male and female Chinese infants between, and including 60 and 90 days of age, who received 3 doses of Oral Poliomyelitis Vaccine (OPV) at 2, 3 and 4 months of age, according to the vaccination policy recommended in China. |
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End point title |
Number of seroprotected subjects against poliovirus types 1, 2 and 3 | ||||||||||||||||||
End point description |
A seroprotected subject was defined as a vaccinated subject with anti-polio types 1, 2 and 3 titers greater than or equal to (≥) 8 effective dose 50 (ED50).
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End point type |
Primary
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End point timeframe |
At Month 3, one month after the third vaccine dose
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Statistical analysis title |
Non-inferiority of IPV as compared to OPV | ||||||||||||||||||
Statistical analysis description |
Non-inferiority of IPV vaccine as compared to OPV vaccine in terms of the immune response to poliovirus type 1 one month after the third vaccine dose. Non-inferiority in terms of immunogenicity to poliovirus antigens was demonstrated if the upper limit of the 95% confidence interval (CI) on the group difference [Control Group minus IPV Group] in the percentage of seroprotected subjects was lesser than or equas to (≤) 10%.
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Comparison groups |
Control Group v Poliorix Group
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Number of subjects included in analysis |
602
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||
Method |
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Parameter type |
Difference in seroprotection rate | ||||||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-1.28 | ||||||||||||||||||
upper limit |
1.24 | ||||||||||||||||||
Statistical analysis title |
Non-inferiority of IPV as compared to OPV | ||||||||||||||||||
Statistical analysis description |
Non-inferiority of IPV vaccine as compared to OPV vaccine in terms of the immune response to poliovirus type 2 one month after the third vaccine dose. Non-inferiority in terms of immunogenicity to poliovirus antigens was demonstrated if the upper limit of the 95% confidence interval (CI) on the group difference [Control Group minus IPV Group] in the percentage of seroprotected subjects was ≤ 10%.
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Comparison groups |
Poliorix Group v Control Group
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Number of subjects included in analysis |
602
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||
Method |
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Parameter type |
Difference in seroprotection rate | ||||||||||||||||||
Point estimate |
0
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-1.28 | ||||||||||||||||||
upper limit |
1.24 | ||||||||||||||||||
Statistical analysis title |
Non-inferiority of IPV as compared to OPV | ||||||||||||||||||
Statistical analysis description |
Non-inferiority of IPV vaccine as compared to OPV vaccine in terms of the immune response to poliovirus type 3 one month after the third vaccine dose. Non-inferiority in terms of immunogenicity to poliovirus antigens was demonstrated if the upper limit of the 95% confidence interval (CI) on the group difference [Control Group minus IPV Group] in the percentage of seroprotected subjects was ≤ 10%.
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Comparison groups |
Poliorix Group v Control Group
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Number of subjects included in analysis |
602
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Analysis specification |
Pre-specified
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Analysis type |
non-inferiority | ||||||||||||||||||
Method |
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Parameter type |
Difference in seroprotection rate | ||||||||||||||||||
Point estimate |
-1.69
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Confidence interval |
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level |
95% | ||||||||||||||||||
sides |
2-sided
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lower limit |
-3.9 | ||||||||||||||||||
upper limit |
-0.44 |
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End point title |
Number of seroprotected subjects against poliovirus types 1, 2 and 3 | ||||||||||||||||||
End point description |
A seroprotected subject was defined as a vaccinated subject with anti-poliovirus types 1, 2 and 3 titers greater than or equal to (≥) 8 ED50.
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End point type |
Secondary
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End point timeframe |
At Day 0, prior to the first vaccine dose
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No statistical analyses for this end point |
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End point title |
Anti-poliovirus types 1, 2 and 3 antibody titers | ||||||||||||||||||||||||||||||
End point description |
Antibody titers were presented as geometric mean titers (GMTs).
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End point type |
Secondary
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End point timeframe |
Prior to the first vaccine dose (Day 0) and one month after the third vaccine dose (Month 3)
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No statistical analyses for this end point |
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End point title |
Number of subjects with any and grade 3 solicited local symptoms [1] | ||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = Cry when limb is moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. This outcome measure concerns subjects from the IPV Group only.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Days 0–3) post-vaccination period following each vaccine dose and across doses
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Notes [1] - 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: This endpoint is only reporting values for the Poliorix Group. |
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No statistical analyses for this end point |
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End point title |
Number of subjects with any, grade 3 and related solicited general symptoms | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
End point description |
Assessed solicited general symptoms were drowsiness, gastrointestinal symptoms, irritability/fussiness, loss of appetite and fever [defined as axillary temperature higher than (>) 37.0°C degrees Celsius]. Gastrointestinal symptoms included nausea, vomiting, diarrhoea and/or abdominal pain. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = subject did not eat at all. Grade 3 gastrointestinal symptoms = gastrointestinal symptoms that prevented normal activity. Grade 3 fever= temperature > 39°C. Related = symptom assessed by the investigator as causally related to the vaccination.
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End point type |
Secondary
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End point timeframe |
During the 4-day (Days 0 -3) post-vaccination period following each vaccine dose and across doses
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No statistical analyses for this end point |
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End point title |
Number of subjects with any unsolicited adverse events | ||||||||||||
End point description |
An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
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End point type |
Secondary
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End point timeframe |
Within the 31-day (Days 0-30) post-vaccination period
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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 |
Serious adverse events (SAEs) assessed include medical occurrences that results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity.
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End point type |
Secondary
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End point timeframe |
During the entire study period (Day 0 to Month 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 |
Solicited local and general symptoms: during the 4-day (Days 0-3) post-vaccination period. Unsolicited AEs: within the 31-day (Days 0-30) post-vaccination period. SAEs: during the entire study period (from Day 0 up to Month 3).
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Adverse event reporting additional description |
The number of occurrences reported for adverse events were not available for posting. The number of subjects affected by each specific event was indicated as the number of occurrences.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
13.1
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Reporting groups
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Reporting group title |
Control Group
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Reporting group description |
Healthy male and female Chinese infants between, and including 60 and 90 days of age, who received 3 doses of Oral Poliomyelitis Vaccine (OPV) at 2, 3 and 4 months of age, according to the vaccination policy recommended in China. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Poliorix Group
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Reporting group description |
Healthy male and female Chinese infants between, and including 60 and 90 days of age, who received 3 doses of Poliorix (IPV) vaccine at 2, 3 and 4 months of age, administered intramuscularly into the anterolateral side of the right thigh. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Frequency threshold for reporting non-serious adverse events: 5% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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. | |||
None reported |