Vaccine Efficacy Against Rotavirus Diarrhea; Vaccine Given With Routine Childhood Vaccinations in Healthy African Infants

GlaxoSmithKline2,089 enrolled

Overview

The primary objective of this study is to determine if the GSK Biologicals' human rotavirus (HRV) vaccine (pooled HRV groups) given concomitantly with routine expanded program on immunisation (EPI) vaccinations can prevent severe rotavirus gastroenteritis (≥11 on the 20-point Vesikari scoring system \[Ruuska, 1990\]) caused by the circulating wild-type RV strains during the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 5. The primary objective will be reached if the lower limit of the 95% confidence interval (CI) on vaccine efficacy is \>0%. The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

The study will have three groups: Rotarix 3-Dose Group, Rotarix 2-Dose Group and Placebo Group. Three-dose immunisation will be administered in healthy infants at approximately 6, 10, and 14 weeks of age. Routine EPI vaccinations will be administered concomitantly with the study vaccines. This study will also evaluate immunogenicity and safety relative to the placebo.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

2,089

Conditions

Infections, Rotavirus

Interventions

Eligibility

Sex: ALLMin age: 5 WeeksMax age: 10 WeeksHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * 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. * A male or female child between, and including, 5 and 10 weeks of age at the time of the first study vaccination. * Written informed consent obtained from the parent or guardian of the subject who is of legal age * Healthy subjects as established by medical history and clinical examination before entering into the study. * In South Africa, birth weight \> 2000 grams or if weight unknown, gestation period \> 36 weeks. Exclusion Criteria: * Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine(s) within 30 days preceding the first dose of study vaccine, or planned use during the study period. * 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 * Planned administration of a vaccine not foreseen by the study protocol within 14 days before each dose of study vaccine(s) and ending 14 days after. * Chronic administration (defined as more than 14 days) of immunosuppressants since birth. * History of use of experimental rotavirus vaccine. * Previous routine vaccination except Bacille Calmette-Guérin (BCG), hepatitis B virus (HBV) and oral poliovirus (OPV) vaccination at birth * Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract, intussusception or other medical condition determined to be serious by the investigator. * Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination * History of allergic disease or reaction likely to be exacerbated by any component of the vaccine. * Acute disease at the time of enrolment. * Gastroenteritis within 7 days preceding the first study vaccine administration * Previous confirmed occurrence of rotavirus gastroenteritis (RV GE). * A family history of congenital or hereditary immunodeficiency. * Administration of immunoglobulins and/or blood products since birth or planned administration during the study period. * History of any neurologic disorders or seizures. * Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.

Locations (13)

GSK Investigational Site

Bangwe, Blantyre, Malawi

GSK Investigational Site

Limbe, Blantyre, Malawi

GSK Investigational Site

Ndirande, Blantyre, Malawi

GSK Investigational Site

Zingwanga, Blantyre, Malawi

GSK Investigational Site

Brits, South Africa

GSK Investigational Site

Diepkloof, Soweto, South Africa

GSK Investigational Site

Diepsloot, South Africa

GSK Investigational Site

Eldorado Park Ext 9, Soweto, South Africa

GSK Investigational Site

Karenpark, South Africa

GSK Investigational Site

Mamelodi, South Africa

...and 3 more locations

Outcomes

Primary Outcomes

Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain

Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.

Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age

Secondary Outcomes

Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type

Number of subjects presenting with three or more looser than normal stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. Rotavirus types were G1 wild type (WT) and non-G1.

Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age

Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain

Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age

Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain

Time frame: From the first vaccine or placebo dose up to 1 year of age

In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain

Time frame: From 2 weeks after the third dose of vaccine or placebo up to 1 year of age

Number of Subjects Reporting Severe Gastroenteritis of Any Cause

Number of subjects with gastroenteritis (three or more looser than normal stools or watery stools within a day) that scored ≥ 11 on the 20-point Vesikari scoring system.

Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age

Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain

RV GE caused by the circulating wild-type rotavirus strain: three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample collected as soon as possible after the symptoms begin.

Time frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age

For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains

Time frame: During the period from 2 weeks after the last dose of vaccine or placebo until study end

For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains

Time frame: During the period from 1 year of age to study end

For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains

Time frame: During the period from 2 weeks after the last dose of vaccine or placebo until study end

Time frame: During the period from 1 year of age to study end

For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type

Time frame: During the period from 2 weeks after the last dose of vaccine or placebo until study end

Time frame: During the period from 1 year of age to study end

Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out

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. An 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.

Time frame: From the first dose of vaccine or placebo up to end of the study

Number of Subjects Reporting Serious Adverse Events (SAEs)

An 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.

Time frame: From the first dose of vaccine or placebo up to end of the study

Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects

An initially seronegative subject is a subject whose IgA antibody concentration was below the assay cut-off value of 20 Units per milliliter (U/mL) before administration of the first vaccine dose.

Time frame: One month after the last vaccine dose

Number of Seroconverted Subjects

Seroconverted subjects are defined as subjects with appearance of anti-rotavirus IgA antibody concentration ≥ 20 U/mL in subjects initially (i.e. prior to the first dose of vaccine or placebo) seronegative for rotavirus.

Time frame: One month after the last vaccine or placebo dose

Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies

Geometric mean concentrations are given as Units per milliliter (U/mL).

Time frame: One month after the last vaccine or placebo dose

Number of Seropositive Subjects

Seropositive subjects are defined as subjects with anti-rotavirus IgA antibody concentration ≥ 20 U/mL.

Time frame: One month after the last vaccine or placebo dose