Clinical Trial Results:
A phase III, double-blind, randomized, placebo-controlled, multi-country and multi-center study to assess the efficacy and safety of two doses of GSK Biologicals’ oral live attenuated human rotavirus (HRV) vaccine in healthy infants.
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Summary
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EudraCT number |
2015-001541-92 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
07 Jul 2008
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Results information
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Results version number |
v1 |
This version publication date |
13 Apr 2016
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First version publication date |
02 Aug 2015
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Other versions |
v2 |
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 |
444563/028/029/030,107070,72,76
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00329745 | ||
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 Trails Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
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Scientific contact |
Clinical Trails 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 |
19 Jan 2009
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
07 Jul 2008
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Global end of trial reached? |
Yes
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Global end of trial date |
07 Jul 2008
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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 |
•In all subjects, to determine if two doses of GSK Biologicals’ HRV vaccine given concomitantly with routine vaccinations* can prevent severe rotavirus gastroenteritis (RV GE) caused by the circulating wild-type RV strains during the period starting from 2 weeks after Dose 2 until 2 years of age. (*Whenever Oral Polio Vaccination (OPV) is used a minimum 2-week interval should be observed between HRV vaccine and OPV doses.)
•In all subjects, to assess the safety of HRV vaccine with respect to definite intussusception (IS) within 31 days (Day 0-Day 30) after each HRV vaccine dose.
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Protection of trial subjects |
All subjects were supervised closely for at least 30 minutes following vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines. Subjects were followed-up from the time the subject consents to participate in the study until she/he is discharged.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
08 Dec 2003
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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 |
Hong Kong: 2954
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Country: Number of subjects enrolled |
Taiwan: 1084
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Country: Number of subjects enrolled |
Singapore: 4649
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Worldwide total number of subjects |
8687
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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) |
8687
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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 |
- | ||||||||||||||||||||||||
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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. | ||||||||||||||||||||||||
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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 |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||
Roles blinded |
Investigator, Carer, Subject | ||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Rotarix Group | ||||||||||||||||||||||||
Arm description |
During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Rotarix™
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Oral use
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Dosage and administration details |
Oral administration, 2 doses
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Arm title
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Placebo Group | ||||||||||||||||||||||||
Arm description |
During the primary study (NCT00197210) subjects received two oral doses of placebo. | ||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Injection
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Routes of administration |
Oral use
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Dosage and administration details |
Oral administration, 2 doses
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Baseline characteristics reporting groups
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Reporting group title |
Rotarix Group
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Reporting group description |
During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Group
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Reporting group description |
During the primary study (NCT00197210) subjects received two oral doses of placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Rotarix Group
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Reporting group description |
During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine. | ||
Reporting group title |
Placebo Group
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Reporting group description |
During the primary study (NCT00197210) subjects received two oral doses of placebo. | ||
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End point title |
Number of subjects with severe rotavirus gastroenteritis (RV GE) caused by the circulating wild-type rotavirus strains [1] | ||||||||||||
End point description |
Severe RV GE is an episode of severe GE in which rotavirus other than vaccine strain was identified in a GE stool sample. Note that this outcome measure is secondary in the study protocol. We have reported it here as primary outcome measure, since none of the primary outcome measures in the study protocol pertain to the time point (Year 3 follow-up) presented in this summary.
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End point type |
Primary
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End point timeframe |
From Year 2 up to Year 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: The analysis of the primary endpoint was descriptive i.e. no statistical hypothesis test was performed. |
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects reporting serious adverse events (SAEs) | ||||||||||||
End point description |
An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above.
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End point type |
Secondary
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End point timeframe |
From the end of the primary study up to Year 3
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information [1]
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Timeframe for reporting adverse events |
The occurrence of reported AEs (all/related) was not available and is encoded as equal to the number of subjects affected.
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Adverse event reporting additional description |
Adverse events were not systematically followed up in this study. Only the adverse events (and serious adverse events) leading to subject withdrawal or drop-out were collected.
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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 |
11.1
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Reporting groups
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Reporting group title |
Rotarix Group
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Reporting group description |
During the primary study (NCT00197210) subjects received two oral doses of Rotarix™ vaccine. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Group
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Reporting group description |
During the primary study (NCT00197210) subjects received two oral doses of placebo. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Notes [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported. Justification: No non-serious adverse events were reported during the course of the study as per the protocol. |
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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? Yes | |||
Date |
Amendment |
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11 Jun 2003 |
Rationale:
Evaluated the safety of GSK Biologicals’ HRV vaccine, administration of OPV will be deferred from the study vaccine administration by minimum 2 weeks. (1, 2)
Interim analysis of an ongoing study (rota-021) in Latin America did not establish the non-inferiority of the all-in-one formulation planned to be used in study 023 as compared to the initial formulation. The initial formulation was therefore used instead of all-in-one formulation.
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24 Feb 2004 |
Unlike planned, Malaysia and Thailand did not participate in this study, for logistical and internal organizational reasons. This led to reduction of the sample size. The power was recalculated for the reduced sample size.
Because of the overall reduction in sample size, it was decided that all subjects will be followed for efficacy and safety until they reach 2 years of age, instead of only a subset.
The method for power computation for the primary safety objective and the statistical analysis section on safety was adapted to reflect a recommendation from the statistician from the IDMC.
An exclusion criterion was added to exclude infants who could have rare underlying congenital abnormalities caused by consanguinity.
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26 Apr 2005 |
An interim analysis on the safety and immunogenicity data was performed in June 2005. Unblinding at the level of individual data was restricted to the Statistician and database administration until the study end. An interim study report was written for this time point. |
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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 | |||
