Clinical Trial Results:
A phase IIIb, randomized, double-blind, placebo-controlled study to explore the existence of horizontal transmission of the RIX4414 vaccine strain between twins within a family.
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Summary
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EudraCT number |
2015-001542-29 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
13 Feb 2008
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Results information
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Results version number |
v2(current) |
This version publication date |
03 Mar 2018
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First version publication date |
15 Jul 2015
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Other versions |
v1 |
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 |
106260
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00396630 | ||
WHO universal trial number (UTN) |
- | ||
Other trial identifiers |
US NIH Grant Number: BB-IND #9231 | ||
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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 |
24 Dec 2008
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
23 Jan 2008
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Global end of trial reached? |
Yes
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Global end of trial date |
13 Feb 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 |
Estimate the rate of transmission of the HRV vaccine strain to twin receiving placebo using RV detection by ELISA and vaccine strain identification using appropriate molecular technique.
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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 a rare anaphylactic reaction following the administration of vaccines.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
23 Jan 2007
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
Yes
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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 |
Dominican Republic: 200
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Worldwide total number of subjects |
200
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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) |
200
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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 |
Within each pair of twins enrolled in the study, one subject was assigned to the Rotarix Group and one to the Placebo Group. | |||||||||||||||||||||
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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 |
Subject, Investigator, Assessor | |||||||||||||||||||||
Blinding implementation details |
An open-label dose of HRV vaccine was administered at Visit 3 to all subjects in each group who were aged less than 6 months at Visit 3 as a benefit to the placebo group for participation in the study. Visits 1, 2, 3 and 4 corresponded to Day 0, Week 7, Week 13 and Week 17.
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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 |
All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | |||||||||||||||||||||
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 |
Powder and solvent for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Two-dose oral vaccination.
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Arm title
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Placebo Group | |||||||||||||||||||||
Arm description |
All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | |||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||
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 |
Powder and solvent for oral suspension
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Routes of administration |
Oral use
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Dosage and administration details |
Two-dose oral administration.
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Baseline characteristics reporting groups
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Reporting group title |
Rotarix Group
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Reporting group description |
All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Group
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Reporting group description |
All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Rotarix Group
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Reporting group description |
All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | ||
Reporting group title |
Placebo Group
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Reporting group description |
All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | ||
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End point title |
Presence of rotavirus vaccine strain in any stool sample from twin receiving placebo. [1] [2] | ||||||||
End point description |
Number of subjects in the Placebo Group with rotavirus vaccine strain in at least one stool sample. This outcome measure concerns subjects in the Placebo Group only.
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End point type |
Primary
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End point timeframe |
On the day of each vaccine/placebo dose, then three times weekly for 6 consecutive weeks starting after each vaccine/placebo dose and on the day of Visit 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. [2] - 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 outcome measure concerns subjects in the Placebo Group only. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Duration of human rotavirus (HRV) shedding per study group. | ||||||||||||||||||
End point description |
Duration of shedding in the Placebo Group= number of days between first and last stool sample positive (+) for rotavirus (RV) antigen and in the Rotarix Group= number of days between the day of vaccination and the date of last stool sample + for RV antigen.
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End point type |
Secondary
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End point timeframe |
From Day 0 up to Week 13
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Anti-rotavirus immunoglobulin A (IgA) antibody seroconversion. | ||||||||||||
End point description |
Number of initially seronegative subjects with anti-rotavirus IgA antibody concentration ≥ 20 Units/milliliter (U/mL), 1 month after the second dose.
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End point type |
Secondary
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End point timeframe |
At Visit 3 (Week 13)
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Anti-rotavirus IgA antibody concentration. | |||||||||||||||
End point description |
Anti-rotavirus IgA antibody concentrations are given as geometric mean concentrations (GMC) with 95% Confidence Intervals
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End point type |
Secondary
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End point timeframe |
At Visit 3 (Week 13)
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Number of subjects with gastroenteritis (GE) and rotavirus gastroenteritis (RV GE) episodes. | |||||||||||||||
End point description |
GE episodes were defined as diarrhea (passage of three or more looser than normal stools within a day) with or without vomiting. RV GE episodes were defined as GE episodes for which the stool sample temporally closest to the onset day of the GE episode was positive for rotavirus by Enzyme Linked Immunosorbent Assay (ELISA).
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End point type |
Secondary
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End point timeframe |
Until Visit 4 (Week 17) for GE and until Visit 3 (Week 13) for RV GE
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| No statistical analyses for this end point | ||||||||||||||||
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End point title |
Number of subjects reporting unsolicited Adverse Events (AEs). | ||||||||||||
End point description |
An AE is 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.
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End point type |
Secondary
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End point timeframe |
Within 31 days after any dose.
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of subjects reporting any Serious Adverse Events (SAEs). | ||||||||||||
End point description |
A serious adverse event (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 |
Up to Visit 4
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Number of genetic variation differences detected by sequencing of genomic mutations in the HRV vaccine strain after transmission. | ||||||||||||
End point description |
Dissimilar amino acid substitutions in the HRV vaccine strain isolated from the twin receiving placebo, when compared to the genetic variation of HRV vaccine strain isolated from the Rotarix vaccine recipients, were counted as genetic variation differences.
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End point type |
Secondary
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End point timeframe |
During the entire study period (up to Visit 4, Week 17).
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| No statistical analyses for this end point | |||||||||||||
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End point title |
Live viral vaccine load in the stool of the twin receiving placebo in case of transmission. [3] | ||||||||
End point description |
Number of subjects in the Placebo Group with live virus identified in at least one stool sample in case of transmission.
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End point type |
Secondary
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End point timeframe |
During the entire study period (up to Visit 4, Week 17).
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| Notes [3] - 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 outcome measure concerns subjects in the Placebo Group only. |
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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: within 31 days after any doses (Day 0-30) and Serious adverse events: during the entire study period (Day 0 to Week 17).
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Adverse event reporting additional description |
The number of occurrences reported for solicited symptoms, adverse events, and serious 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 |
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 |
All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Group
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Reporting group description |
All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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17 Aug 2006 |
This amendment was implemented in order to comply with a request from the MOH in the Dominican Republic reviewing the study protocol. They specifically requested that subjects allocated to the placebo group receive Rotarix vaccination at study end. Given the upper age limit to administer Rotarix vaccination, it has been agreed to give a single open-label Rotarix dose before 6 months of age. To facilitate the study amendment design it has been proposed to give all subjects a dose of Rotarix at Visit 3 given the fact that three-dose regimens have been explored previously and shown to be safe. As an additional study benefit for all subjects Prevnar vaccination will be offered to all study participants at the discretion of the investigator. |
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23 May 2007 |
This amendment was implemented in order to comply with a request from the MOH in the Dominican Republic reviewing the study protocol. They specifically requested that subjects allocated to the placebo group receive Rotarix™ vaccination at study end. Given the upper age limit to administer Rotarix™ vaccination, it has been agreed to give a single open-label Rotarix™ dose before 6 months of age. To facilitate the study amendment design it has been proposed to give all subjects a dose of Rotarix™ at Visit 3 given the fact that three-dose regimens have been explored previously and shown to be safe. As an additional study benefit for all subjects Prevnar™ vaccination will be offered to all study participants at the discretion of the investigator. |
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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 | |||
