A Study to Evaluate Immune Response and Safety of Two Doses of GSK Biologicals' HRV Liquid Vaccine in Healthy Infants.

Study Overview
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Brief Summary
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This study will provide data on the immune response and safety of GSK Biologicals' HRV liquid vaccine when given along with the routine infant immunizations in Philippines.

Official Title
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Immunogenicity and Safety of Two Doses of GlaxoSmithKline (GSK) Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Liquid Vaccine (GSK 357941A) in Healthy Infants.

Conditions
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Infections, Rotavirus, Rotavirus Vaccines

Intervention / Treatment
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* Biological: Rotarix™
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants between, and including, 5-10 weeks of age at the time of the first dose of HRV liquid vaccine or placebo. Birth weight of the subject should be > 2000 grams. Written informed consent obtained from the parent or guardian of the subject. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. Planned administration/ administration of a vaccine not foreseen by the study protocol except for DTPw, HBV and OPV vaccines within 14 days before each dose of HRV liquid vaccine or placebo and ending 14 days after. BCG is administered at birth according to the local EPI. Concurrently participating in another clinical study, at any time during the study period. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of allergic disease or reactions likely to be exacerbated by any component of the HRV liquid vaccine or placebo. Acute disease at the time of enrolment. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.

Ages Eligible for Study
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Minimum Age: 5 Weeks
Maximum Age: 10 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PLACEBO-ROTARIX-ROTARIX GROUP<br>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. | Biological: Rotarix™<br>* oral doses<br>Biological: Placebo<br>* oral dose<br>|
| Experimental: ROTARIX-PLACEBO-ROTARIX GROUP<br>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. | Biological: Rotarix™<br>* oral doses<br>Biological: Placebo<br>* oral dose<br>|
| Placebo Comparator: PLACEBO GROUP<br>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. | Biological: Placebo<br>* oral dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibody | 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. | At Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Seroconverted Subjects for Anti-RV IgA Antibody | 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. | At Month 3 | 
| Serum IgA Antibody Concentrations Against Rotavirus | 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. | At Month 3 | 
| Number of Subjects Reporting Grade 2 or Grade 3 Fever, Vomiting or Diarrhea | 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 (≤) 39.5degrees 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. | During the 8-day (Days 0-7) period following each dose of study vaccine or placebo and across doses | 
| Number of Subjects Reporting Any, Grade 3 and Related Solicited General Symptoms | Assessed solicited general symptoms were cough/runny nose, diarrhea, fever (rectally), irritability, loss of appetite and vomiting. Any = any solicited symptom irrespective 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. Grade 3 vomiting = ≥ 3 episodes of vomiting/ day. Related = symptom considered by the investigator to have a causal relationship to study vaccination. | During the 8-day (Days 0-7) period following each dose of study vaccine or placebo and across doses | 
| Number of Subjects Reporting RV in Gastroenteritis (GE) Episodes | Presence of RV (vaccine strain or wild-type) in GE stools. | From Dose 1 of study vaccine or placebo (at Day 0) up to Month 3 | 
| Number of Subjects Reporting Any Unsolicited Adverse Event (AE) | 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. | During the 31-day (Days 0-30) period following any study vaccine dose or placebo | 
| Number of Subjects With Serious Adverse Events (SAEs) | 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. | During the entire study period (from Day 0 to Month 3) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Placebo, Double blind, Gastroenteritis, Randomized, Oral live attenuated human rotavirus liquid vaccine