Efficacy, Immunogenicity and Safety of Two Doses of GlaxoSmithKline (GSK) Biologicals' Oral Live Attenuated Liquid Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 3,340
- Locations
- 4
- Primary Endpoint
- Number of Subjects With Severe Episode(s) of Rotavirus Gastroenteritis (RVGE) Caused by the Circulating Wild Type (WT) Strains
Study Overview
Brief Summary
The purpose of this study is to assess the efficacy, immunogenicity and safety of GSK Biologicals' liquid human rotavirus vaccine in healthy Chinese infants 6 to 16 weeks of age.
Detailed Description
Subjects can receive routine childhood vaccination according to the expanded program of immunisation recommendations in China.
There will be two treatment groups (liquid human rotavirus vaccine and placebo). The study will also have two immunogenicity subgroups comprising of few subjects from both the treatment groups. The immunogenicity subgroup 1 will assess the immunogenicity of the liquid human rotavirus vaccine and the immunogenicity subgroup 2 will assess the immunogenicity of liquid human rotavirus vaccine and also the immunogenicity of oral poliovirus vaccine and diphtheria tetanus and acellular pertussis vaccine given concomitantly with liquid human rotavirus vaccine or placebo.
This protocol posting has been updated following the Protocol Amendment 2, dated 05 August 2011. The impacted section in the protocol posting is: Outcome Measures Section.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 6 Weeks to 16 Weeks (Child)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Subjects who the investigator believes that their parents/Legally Acceptable Representatives can and will comply with the requirements of the protocol.
- •A male or female infant of Chinese origin between, and including, 6 and 16 weeks of age at the time of the first vaccination.
- •Written informed consent obtained from the parents/Legally Acceptable Representatives of the subject.
- •Healthy subjects as established by medical history and clinical examination before entering into the study.
- •Born after a gestation period of 36 to 42 weeks inclusive.
Exclusion Criteria
- •Child in care.
- •Use of any investigational or non-registered product 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 since birth.
- •Planned administration/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 the first dose of the human rotavirus vaccine or placebo except for the routine childhood vaccinations.
- •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.
- •Any clinically significant history of gastrointestinal disease including any uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for intussusception .
- •Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
- •Family history of congenital or hereditary immunodeficiency.
- •History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
- •Major congenital defects or serious chronic illness.
- •History of confirmed rotavirus gastroenteritis.
- •Acute disease and/or fever at the time of enrolment.
- •Gastroenteritis within 7 days preceding the study vaccine or placebo administration.
- •Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
- •In addition to the criteria mentioned above, the following criteria will be applicable to all subjects in the immunogenicity subgroup 2:
- •History of diphtheria, tetanus and pertussis disease.
- •History of seizures or progressive neurological disease.
- •Previous vaccination against diphtheria, tetanus, pertussis and poliomyelitis.
Arms & Interventions
Rotarix Group
Subjects aged between and including 6 and 16 weeks at the time of first vaccination received 2 doses of Rotarix™ vaccine, liquid formulation, at Day 0 and at Month 1. As part of the routine childhood vaccination according to the Expanded Program of Immunization (EPI) recommendations in China, subjects in this group also received 3 doses of Infanrix™ vaccine and 3 doses of the oral poliovirus vaccine manufactured by the Institute of Medical Biology of the Chinese Academy of Medical Sciences (OPV). The Infanrix™ and the OPV vaccines were administered independently of (Sub-cohort 1) or concomitantly with (Sub-cohort 2) the Rotarix™ vaccine. When administered concomitantly, subjects received the 3 doses of Infanrix™ vaccine at Months 1, 2 and 3, and the 3 doses of the OPV vaccine at Day 0, Month 1 and Month 2. The Rotarix™ and OPV vaccines were administered orally; the Infanrix™ vaccine was administered intramuscularly in the left anterolateral thigh.
Intervention: GSK Biologicals' liquid human rotavirus vaccine 444563 (Biological)
Rotarix Group
Subjects aged between and including 6 and 16 weeks at the time of first vaccination received 2 doses of Rotarix™ vaccine, liquid formulation, at Day 0 and at Month 1. As part of the routine childhood vaccination according to the Expanded Program of Immunization (EPI) recommendations in China, subjects in this group also received 3 doses of Infanrix™ vaccine and 3 doses of the oral poliovirus vaccine manufactured by the Institute of Medical Biology of the Chinese Academy of Medical Sciences (OPV). The Infanrix™ and the OPV vaccines were administered independently of (Sub-cohort 1) or concomitantly with (Sub-cohort 2) the Rotarix™ vaccine. When administered concomitantly, subjects received the 3 doses of Infanrix™ vaccine at Months 1, 2 and 3, and the 3 doses of the OPV vaccine at Day 0, Month 1 and Month 2. The Rotarix™ and OPV vaccines were administered orally; the Infanrix™ vaccine was administered intramuscularly in the left anterolateral thigh.
Intervention: Infanrix™ (Biological)
Rotarix Group
Subjects aged between and including 6 and 16 weeks at the time of first vaccination received 2 doses of Rotarix™ vaccine, liquid formulation, at Day 0 and at Month 1. As part of the routine childhood vaccination according to the Expanded Program of Immunization (EPI) recommendations in China, subjects in this group also received 3 doses of Infanrix™ vaccine and 3 doses of the oral poliovirus vaccine manufactured by the Institute of Medical Biology of the Chinese Academy of Medical Sciences (OPV). The Infanrix™ and the OPV vaccines were administered independently of (Sub-cohort 1) or concomitantly with (Sub-cohort 2) the Rotarix™ vaccine. When administered concomitantly, subjects received the 3 doses of Infanrix™ vaccine at Months 1, 2 and 3, and the 3 doses of the OPV vaccine at Day 0, Month 1 and Month 2. The Rotarix™ and OPV vaccines were administered orally; the Infanrix™ vaccine was administered intramuscularly in the left anterolateral thigh.
Intervention: Institute of Medical Biology Chinese Academy of Medical Sciences' Oral poliovirus vaccine (OPV) (Biological)
Placebo Group
Subjects aged between and including 6 and 16 weeks at the time of first vaccination received 2 doses of Placebo at Day 0 and at Month 1. As part of the routine childhood vaccination according to the Expanded Program of Immunization (EPI) recommendations in China, subjects in this group also received 3 doses of Infanrix™ vaccine and 3 doses of the oral poliovirus vaccine manufactured by the Institute of Medical Biology of the Chinese Academy of Medical Sciences (OPV). The Infanrix™ and the OPV vaccine were administered independently of (Sub-cohort 1) or concomitantly with (Sub-cohort 2) the Placebo. When administered concomitantly, subjects received the 3 doses of Infanrix™ vaccine at Months 1, 2 and 3, and the 3 doses of the OPV vaccine at Day 0, Month 1 and Month 2. The Placebo and the OPV vaccine were administered orally; the Infanrix™ vaccine was administered intramuscularly in the left anterolateral thigh.
Intervention: Placebo (Biological)
Placebo Group
Subjects aged between and including 6 and 16 weeks at the time of first vaccination received 2 doses of Placebo at Day 0 and at Month 1. As part of the routine childhood vaccination according to the Expanded Program of Immunization (EPI) recommendations in China, subjects in this group also received 3 doses of Infanrix™ vaccine and 3 doses of the oral poliovirus vaccine manufactured by the Institute of Medical Biology of the Chinese Academy of Medical Sciences (OPV). The Infanrix™ and the OPV vaccine were administered independently of (Sub-cohort 1) or concomitantly with (Sub-cohort 2) the Placebo. When administered concomitantly, subjects received the 3 doses of Infanrix™ vaccine at Months 1, 2 and 3, and the 3 doses of the OPV vaccine at Day 0, Month 1 and Month 2. The Placebo and the OPV vaccine were administered orally; the Infanrix™ vaccine was administered intramuscularly in the left anterolateral thigh.
Intervention: Infanrix™ (Biological)
Placebo Group
Subjects aged between and including 6 and 16 weeks at the time of first vaccination received 2 doses of Placebo at Day 0 and at Month 1. As part of the routine childhood vaccination according to the Expanded Program of Immunization (EPI) recommendations in China, subjects in this group also received 3 doses of Infanrix™ vaccine and 3 doses of the oral poliovirus vaccine manufactured by the Institute of Medical Biology of the Chinese Academy of Medical Sciences (OPV). The Infanrix™ and the OPV vaccine were administered independently of (Sub-cohort 1) or concomitantly with (Sub-cohort 2) the Placebo. When administered concomitantly, subjects received the 3 doses of Infanrix™ vaccine at Months 1, 2 and 3, and the 3 doses of the OPV vaccine at Day 0, Month 1 and Month 2. The Placebo and the OPV vaccine were administered orally; the Infanrix™ vaccine was administered intramuscularly in the left anterolateral thigh.
Intervention: Institute of Medical Biology Chinese Academy of Medical Sciences' Oral poliovirus vaccine (OPV) (Biological)
Outcomes
Primary Outcomes
Number of Subjects With Severe Episode(s) of Rotavirus Gastroenteritis (RVGE) Caused by the Circulating Wild Type (WT) Strains
Time Frame: From Month 1 ½ to Month 21
A gastroenteritis episode was classified positive for rotavirus (RV) and caused by the circulating wild-type (WT) RV strains if RV other than the vaccine strain was identified in a stool sample collected during the episode. Severe RVGE was defined as an episode of RV GE with score equal to or higher than (\>=) 11 on a 20-point Vesikari scoring system.
Secondary Outcomes
- Number of Subjects With Any Solicited Local Symptoms Following Dose 2 of the Rotarix Vaccine/Placebo(Within the 8-day (Days 0-7) follow-up periods following Dose 2 of the Rotarix vaccine/placebo)
- Number of Seroconverted Subjects for Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibodies(At Month 2 and at 12 months of age)
- Number of Subjects With Any Episode(s) of Rotavirus Gastroenteritis (RVGE) of Any Type.(From Month 1 ½ to Month 21)
- Number of Subjects With Severe Episode(s) of Rotavirus Gastroenteritis (RVGE) of Any Type.(From Month 1 ½ to Month 21)
- Number of Subjects With Any and Severe Gastroenteritis (GE) Due to Any Cause(From Month 1 ½ to Month 21)
- Number of Subjects With Any Solicited General Symptoms Following Administration of the Co-administered EPI Vaccines(Within the 8-day (Days 0-7) follow-up periods following Doses 1 and 2 of the OPV vaccine and Dose 1 of the Infanrix vaccine)
- Number of Subjects With Any Unsolicited Adverse Events (AEs)(Within the 31-day (Days 0-30) follow-up periods following any dose of the Rotarix vaccine or placebo)
- Number of Subjects Seropositive for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies.(At Day 0 and at Month 4)
- Number of Subjects With Any Episode(s) of Rotavirus Gastroenteritis (RVGE) Caused by the Circulating Wild-type Strains(From Month 1 ½ to Month 21)
- Number of Subjects With Any Serious Adverse Events (SAEs)(Throughout the entire study period (from Day 0 to Study End at Month 21))
- Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations.(At Day 0, Month 2 and at 12 months of age)
- Anti-Diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations(At Day 0 and at Month 4)
- Number of Subjects With Episodes of Rotavirus Gastroenteritis (RVGE) Caused by the Circulating Wild Type (WT) Strains Requiring Hospitalization(From Month 1 ½ to Month 21)
- Number of Subjects With Any Solicited General Symptoms Following Vaccination With the Rotarix Vaccine/Placebo(Within the 8-day (Days 0-7) follow-up periods after any dose of Rotarix vaccine/placebo)
- Number of Subjects Seroprotected Against Diphtheria and Tetanus(At Day 0 and at Month 4)
- Number of Subjects Seroprotected Against Poliovirus Types 1, 2 and 3.(At Day 0 and at Month 4)
- Titers for Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibodies(At Day 0 and at Month 4)
- Number of Seroconverted Subjects for Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibodies.(At Month 2 and at 12 months of age)
- Number of Subjects Seropositive for Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibodies.(At Day 0, Month 2 and at 12 months of age)
- Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations(At Day 0, Month 2 and at 12 months of age)
- Concentrations of Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies(At Day 0 and at Month 4)