Clinical Trial Results:
A phase II, randomized, double-blind, placebo-controlled study to evaluate the immunogenicity, reactogenicity and safety of two doses of GlaxoSmithKline (GSK) Biologicals’ oral live attenuated human rotavirus (HRV) liquid vaccine, when given to healthy infants, in Philippines
Summary
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EudraCT number |
2015-001544-11 |
Trial protocol |
Outside EU/EEA |
Global end of trial date |
04 Sep 2007
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Results information
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Results version number |
v3(current) |
This version publication date |
28 Mar 2023
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First version publication date |
08 Jul 2015
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Other versions |
v1 (removed from public view) , 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 |
109216
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT00432380 | ||
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, 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 |
04 Sep 2007
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Sep 2007
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Sep 2007
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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 immunogenicity of GSK Biologicals’ HRV liquid vaccine versus placebo, in terms of anti-rotavirus Immunoglobulin A (IgA) antibody seroconversion at Month 3 (i.e. Visit 4), when administered concomitantly with the second and third routine EPI immunization.
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Protection of trial subjects |
The subjects were observed closely for at least 30 minutes following the administration of vaccines, with appropriate medical treatment readily available in case of a rare anaphylactic reaction.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
09 Mar 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 |
Philippines: 375
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Worldwide total number of subjects |
375
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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) |
375
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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 |
- | ||||||||||||||||||||||||
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 trial (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, Carer, Assessor | ||||||||||||||||||||||||
Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo-Rotarix-Rotarix Group | ||||||||||||||||||||||||
Arm description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 2 oral doses of Rotarix liquid vaccine at Month 1 and Month 2, and a single oral dose of placebo at Day 0. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Rotarix
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Investigational medicinal product code |
SUB22357
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Other name |
HUMAN ROTAVIRUS RIX4414 STRAIN (LIVE ATTENUATED)
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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 oral doses of the liquid HRV vaccine administered at Months 1 and 2.
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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 |
1 oral dose of placebo administered at Day 0.
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Arm title
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Rotarix-Placebo-Rotarix Group | ||||||||||||||||||||||||
Arm description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 2 oral doses of Rotarix liquid vaccine at Day 0 and Month 2, and a single oral dose of placebo at Month 1. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||||||||||||||||||||||||
Arm type |
Experimental | ||||||||||||||||||||||||
Investigational medicinal product name |
Rotarix
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Investigational medicinal product code |
SUB22357
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Other name |
HUMAN ROTAVIRUS RIX4414 STRAIN (LIVE ATTENUATED)
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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 oral doses of the liquid HRV vaccine administered at Day 0 and Month 2.
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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 |
1 oral dose of placebo administered at Month 1.
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Arm title
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Placebo Group | ||||||||||||||||||||||||
Arm description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 3 oral doses of placebo at Day 0, Month 1 and Month 2. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||||||||||||||||||||||||
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 |
Injection
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Routes of administration |
Oral use
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Dosage and administration details |
Three oral doses of placebo administered at Day 0, Months 1 and 2.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo-Rotarix-Rotarix Group
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Reporting group description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 2 oral doses of Rotarix liquid vaccine at Month 1 and Month 2, and a single oral dose of placebo at Day 0. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rotarix-Placebo-Rotarix Group
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Reporting group description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 2 oral doses of Rotarix liquid vaccine at Day 0 and Month 2, and a single oral dose of placebo at Month 1. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Group
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Reporting group description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 3 oral doses of placebo at Day 0, Month 1 and Month 2. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo-Rotarix-Rotarix Group
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Reporting group description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 2 oral doses of Rotarix liquid vaccine at Month 1 and Month 2, and a single oral dose of placebo at Day 0. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||
Reporting group title |
Rotarix-Placebo-Rotarix Group
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Reporting group description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 2 oral doses of Rotarix liquid vaccine at Day 0 and Month 2, and a single oral dose of placebo at Month 1. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||
Reporting group title |
Placebo Group
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Reporting group description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 3 oral doses of placebo at Day 0, Month 1 and Month 2. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. |
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End point title |
Number of seroconverted subjects for Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibody [1] [2] | ||||||||
End point description |
Seroconversion was defined as the appearance of anti-RV IgA antibody concentrations greater than or equal to (≥) 20 units per milliliter (U/mL) in subjects initially (i.e. prior to the first dose of Rotarix vaccine or placebo) seronegative, when administered concomitantly with the second and third routine EPI immunization. This outcome measure only concerns subjects in the Placebo-Rotarix-Rotarix Group.
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End point type |
Primary
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End point timeframe |
At Month 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: No statistical analyses for this end point. [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: No statistical analyses for this end point. |
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No statistical analyses for this end point |
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End point title |
Number of seroconverted subjects for Anti-RV IgA antibody [3] | ||||||||
End point description |
Seroconversion was defined as the appearance of anti-RV IgA antibody concentrations ≥ 20 U/mL in subjects initially (i.e. prior to the first dose of Rotarix vaccine or placebo) seronegative, when administered concomitantly with the first and third routine EPI immunization. This outcome measure only concerns subjects in the Rotarix-Placebo-Rotarix Group.
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End point type |
Secondary
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End point timeframe |
At Month 3
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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: No statistical analyses for this end point. |
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No statistical analyses for this end point |
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End point title |
Serum IgA Antibody Concentrations Against Rotavirus [4] | |||||||||||||||
End point description |
Antibody concentrations were presented as geometric mean concentrations (GMCs), expressed in units per milliliter (U/mL). This outcome measure only concerns subjects in Placebo-Rotarix-Rotarix and Rotarix-Placebo-Rotarix Groups.
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End point type |
Secondary
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End point timeframe |
At Month 3
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Notes [4] - 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: No statistical analyses for this end point. |
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting grade “2” or grade “3” fever, vomiting or diarrhea | ||||||||||||||||||||||||||||
End point description |
Any symptom = occurrence of the symptom (i.e. fever or vomiting or diarrhea) regardless of intensity grade or relationship to vaccination. Grade 2 fever = Rectal temperature greater than (>) 38.5 – less than or equal to (≤) 39.5 degrees Celsius (°C) or axillary temperature > 38.0 – ≤ 39.0°C, Grade 3 fever = Rectal temperature > 39.5°C or axillary temperature > 39.0°C. Grade 2 vomiting = 2 episodes of vomiting/ day. Grade 3 vomiting = 3 or more episodes of vomiting/ day. Grade 2 diarrhea = 4-5 looser than normal stools/ day. Grade 3 diarrhea = 6 or more looser than normal stools/ day.
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End point type |
Secondary
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End point timeframe |
During the 8-day (Day 0-Day 7) period following each dose of study vaccine or placebo and across doses
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting any, grade 3 and related solicited general symptoms | ||||||||||||||||||||||||||||
End point description |
Assessed solicited general symptoms were cough/runny nose, diarrhea, fever (rectally), irritability, loss of appetite and vomiting. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. Grade 3 Cough/runny nose = cough/runny nose which prevented daily activity, Grade 2 Diarrhea: 4-5 looser than normal stools/ day, Grade 3 Diarrhea = ≥ 6 looser than normal stools/ day, Grade 3 Irritability = crying that could not be comforted/ prevented normal activity, Grade 3 Loss of appetite = not eating at all, Grade 2 Vomiting= 2 episodes of vomiting/ day and Grade 3 Vomiting = ≥ 3 episodes of vomiting/ day. Related = symptom considered by the investigator to have a causal relationship to study vaccination.
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End point type |
Secondary
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End point timeframe |
During the 8-day (Day 0-Day 7) period following each dose of study vaccine or placebo and across doses
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No statistical analyses for this end point |
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End point title |
Number of subjects reporting any unsolicited adverse event | ||||||||||||||||
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. Any was defined as an adverse event (AE) reported in addition to those solicited during the clinical study. Any solicited symptom with onset outside the specified period of follow-up for solicited symptoms was 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 0-Day 30) period following any study vaccine dose or placebo
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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 any untoward medical occurrences that results in death, are life threatening, requires hospitalization or prolongation of hospitalization, result in disability/incapacity or 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 |
During the entire study period (from 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 symptoms were collected during the 8-day (Days 0-7) post vaccination period. Unsolicited AEs were collected during the 31 day (Days 0-30) post vaccination. SAEs were collected throughout the entire study period (Months 0 to 3).
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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 |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
10.1
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Reporting groups
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Reporting group title |
Placebo-Rotarix-Rotarix Group
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Reporting group description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 2 oral doses of Rotarix liquid vaccine at Month 1 and Month 2, and a single oral dose of placebo at Day 0. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Rotarix-Placebo-Rotarix Group
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Reporting group description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 2 oral doses of Rotarix liquid vaccine at Day 0 and Month 2, and a single oral dose of placebo at Month 1. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo Group
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Reporting group description |
Healthy male or female infants between, and including, 5 to 10 weeks of age, were administered 3 oral doses of placebo at Day 0, Month 1 and Month 2. Subjects also received routine infant vaccinations according to the Expanded Program of Immunization (EPI) recommendations in Philippines. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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25 Jan 2007 |
It was decided to offer all subjects complementary vaccination against Haemophilus influenzae type b (Hib) disease with GSK Biologicals’ Hiberix vaccine after the study end. The protocol was amended to reflect this change. |
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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 |