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

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

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.

Study Overview

• Status: Completed
• Conditions: Infections, Rotavirus; Rotavirus Vaccines
• Intervention / Treatment: Biological: Rotarix™; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 375
• Phase: Phase 2

Contacts and Locations

Study Locations

• Philippines
  • Muntinlupa, Philippines
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PLACEBO-ROTARIX-ROTARIX GROUP; 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™; oral doses; Biological: Placebo; oral dose
Experimental: ROTARIX-PLACEBO-ROTARIX GROUP; 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™; oral doses; Biological: Placebo; oral dose
Placebo Comparator: PLACEBO GROUP; 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; oral dose

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Anh DD, Carlos CC, Thiem DV, Hutagalung Y, Gatchalian S, Bock HL, Smolenov I, Suryakiran PV, Han HH. Immunogenicity, reactogenicity and safety of the human rotavirus vaccine RIX4414 (Rotarix) oral suspension (liquid formulation) when co-administered with expanded program on immunization (EPI) vaccines in Vietnam and the Philippines in 2006-2007. Vaccine. 2011 Mar 3;29(11):2029-36. doi: 10.1016/j.vaccine.2011.01.018. Epub 2011 Jan 21.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2007
• Primary Completion (Actual): September 4, 2007
• Study Completion (Actual): September 4, 2007

Study Registration Dates

• First Submitted: February 6, 2007
• First Submitted That Met QC Criteria: February 6, 2007
• First Posted (Estimate): February 7, 2007

Study Record Updates

• Last Update Posted (Actual): January 2, 2020
• Last Update Submitted That Met QC Criteria: December 27, 2019
• Last Verified: December 1, 2019

More Information

Terms related to this study

• Keywords: Randomized; Gastroenteritis; Placebo; Double blind; Oral live attenuated human rotavirus liquid vaccine
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Reoviridae Infections; Rotavirus Infections
• Other Study ID Numbers: 109216; 2015-001544-11 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• IPD Sharing Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Informed Consent Form
   Information identifier: 109216
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 109216
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 109216
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 109216
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Annotated Case Report Form
   Information identifier: 109216
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 109216
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Dataset Specification
   Information identifier: 109216
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register