Efficacy, Safety, Reactogenicity & Immunogenicity of the Rotarix Vaccine in Japanese Infants

Study Overview
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Brief Summary
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This study is undertaken to provide the regulatory authorities in Japan with immunogenicity, efficacy, safety and reactogenicity data of GSK Biologicals' Human Rotavirus [HRV] vaccine, given as a 2-dose primary vaccination, in healthy Japanese infants aged approximately 2 months at the time of the first dose and previously uninfected with HRV. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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Combined diphtheria and tetanus toxoids and acellular pertussis (DTPa) and Hepatitis B (HBV) vaccines are allowed to be co-administered along with Rotarix vaccine/Placebo.

Official Title
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Efficacy, Safety, Reactogenicity and Immunogenicity Study of the Lyophilised Formulation of Rotarix Vaccine in Healthy Japanese 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 male or female infant between, and including, 6 and 14 weeks (42-104 days) of age at the time of the first vaccination. Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study Healthy subjects as established by medical history and clinical examination before entering into the study. Written informed consent obtained from the parent or guardian of the subject. Born between a gestation period of 36 and 42 weeks inclusive. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the HRV vaccine within 30 days preceding the first dose of HRV vaccine, or planned use during the study period. History of use of experimental rotavirus vaccine. Chronic administration of immunosuppressants or other immune-modifying drugs since birth. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device). Uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for intussusception. Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract or other serious medical condition determined by the investigator. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Previous confirmed occurrence of RV GE. Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required). A family history of congenital or hereditary immunodeficiency. Acute disease at the time of enrolment. Gastroenteritis within 7 days preceding the study vaccine administration. 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: 6 Weeks
Maximum Age: 14 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotarix Group<br>Subjects received 2 oral doses of Rotarix according to a 0, 1 month schedule. | Biological: Rotarix<br>* Two-dose oral vaccination.<br>|
| Placebo Comparator: Placebo Group<br>Subjects received 2 oral doses of placebo according to a 0, 1 month schedule. | Biological: Placebo<br>* Two-dose oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. | From 2 weeks after Dose 2 up to 2 years of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Severe Rotavirus (RV) Gastroenteritis (GE) Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | A subject was considered as reporting severe rotavirus gastroenteritis when the subject scored 11 or more on a 20-point scoring system (Vesikari scoring system). | From 2 weeks after Dose 2 up to 2 years of age | 
| Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of G1 Type | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe RV GE was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system). | From 2 weeks after Dose 2 up to 2 years of age | 
| Number of Subjects Reporting Any Rotavirus (RV) Gastroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains of Non-G1 Types | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe rotavirus gastroenteritis was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system). | From 2 weeks after Dose 2 up to 2 years of age | 
| Number of Subjects Hospitalized Due to Rotavirus (RV) Gastroenteritis (GE) Caused by the Circulating Wild-type RV Strains | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. | From 2 weeks after Dose 2 up to 2 years of age | 
| Number of Subjects Reporting Any Rotavirus (RV) Gatroenteritis (GE) and Severe RV GE Leading to Medical Intervention and Caused by the Circulating Wild-type RV Strains | Rotavirus (RV) gastroenteritis (GE) was defined as an episode of any severity GE leading to a medical intervention occurring at least two weeks after dose 2 in which rotavirus other than vaccine strain is identified in a stool sample collected as soon as possible but preferably not later than 7 days after the start of the episode. Severe rotavirus gastroenteritis was defined as an episode of rotavirus gastroenteritis with score ≥ 11 on a 20-point scoring system (Vesikari scoring system). | From Dose 1 up to 2 years of age | 
| Serum Anti-rotavirus Immunoglobulin A (IgA) Antibody Concentration | Anti-rotavirus immunoglobulin A antibody concentrations are given as geometric mean concentrations (GMCs). Arbitrary 'zero' values were set in the Placebo Group since the GMC was below the assay cut-off value (20 U/mL). | 2 months after Dose 2 | 
| Number of Subjects Seroconverted for Anti-rotavirus Immunoglobulin A (IgA) Antibodies | Seroconversion was defined as the appearance of anti-rotavirus immunoglobulin A antibody concentration ≥ 20 units (U)/milliliter (mL) in subjects initially (i.e. prior to the first dose of rotarix) seronegative. | 2 months after Dose 2 | 
| Number of Subjects Reporting Solicited Symptoms | Solicited symptoms assessed include cough, diarrhoea, fever, irritability, loss of appetite and vomiting. | During the 8-day follow-up period after each dose | 
| Number of Subjects Reporting Unsolicited Adverse Events (AEs) | Unsolicited adverse event (AE) was defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | During the 31-day follow-up period after each dose | 
| Number of Subjects Reporting Serious Adverse Events (SAEs) | Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject. | Up to 2 years of age |