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Study to Assess the Efficacy, Immunogenicity and Safety of Liquid Human Rotavirus Vaccine, in Healthy Chinese Infants

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01171963
First received: July 28, 2010
Last updated: December 19, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Infections, Rotavirus
Biological: GSK Biologicals' liquid human rotavirus vaccine 444563
Biological: Placebo
Biological: Infanrix™
Biological: Institute of Medical Biology Chinese Academy of Medical Sciences' Oral poliovirus vaccine (OPV)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Efficacy, Immunogenicity and Safety of Two Doses of GlaxoSmithKline (GSK) Biologicals' Oral Live Attenuated Liquid Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
    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 Outcome Measures:
  • Number of Subjects With Any Episode(s) of Rotavirus Gastroenteritis (RVGE) Caused by the Circulating Wild-type Strains [ Time Frame: From Month 1 ½ to Month 21 ] [ Designated as safety issue: No ]
    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.

  • Number of Subjects With Any Episode(s) of Rotavirus Gastroenteritis (RVGE) of Any Type. [ Time Frame: From Month 1 ½ to Month 21 ] [ Designated as safety issue: No ]
    A gastroenteritis episode was classified positive for rotavirus (RV) if RV was identified in a stool sample collected during the episode. RV types assessed were G1 Wild Type (G1WT), G2, G3, G9, GX (G type unknown, but not vaccine strain), P4, P8 Wild Type (P8WT), P9, PX (P type unknown, but not vaccine strain) and Pooled Non-G1WT.

  • Number of Subjects With Severe Episode(s) of Rotavirus Gastroenteritis (RVGE) of Any Type. [ Time Frame: From Month 1 ½ to Month 21 ] [ Designated as safety issue: No ]
    A gastroenteritis episode was classified positive for rotavirus (RV) if RV was identified in a stool sample collected during the episode. Severe RVGE was defined as an episode of RVGE with score equal to or higher than (>=) 11 on a 20-point Vesikari scoring system. RV types assessed were G1 Wild Type (G1WT), G2, G3, G9, GX (G type unknown, but not vaccine strain), P4, P8 Wild Type (P8WT), P9, PX (P type unknown, but not vaccine strain) and Pooled Non-G1WT.

  • Number of Subjects With Episodes of Rotavirus Gastroenteritis (RVGE) Caused by the Circulating Wild Type (WT) Strains Requiring Hospitalization [ Time Frame: From Month 1 ½ to Month 21 ] [ Designated as safety issue: No ]
    A gastroenteritis episode was classified positive for rotavirus (RV) and caused by the circulating WT RV strains if RV other than the vaccine strain was identified in a stool sample collected during the episode.

  • Number of Subjects With Any and Severe Gastroenteritis (GE) Due to Any Cause [ Time Frame: From Month 1 ½ to Month 21 ] [ Designated as safety issue: No ]
    Severe GE was defined as an episode of GE with score equal to or higher than (>=) 11 on a 20-point Vesikari scoring system. This outcome measure concerns results for GE episodes due to any cause.

  • Number of Subjects With Any Solicited General Symptoms Following Vaccination With the Rotarix™ Vaccine/Placebo [ Time Frame: Within the 8-day (Days 0-7) follow-up periods after any dose of Rotarix™ vaccine/placebo ] [ Designated as safety issue: No ]
    Assessed solicited general symptoms were fever,defined as axillary temperature (T) above or equal to [>=] 37.5 degrees Celsius [°C] (if GSK scale) or >= 37.1°C (if Chinese scale), fussiness/irritability, loss of appetite, cough/runny nose, diarrhea and vomiting. Any = any occurrence of the specified solicited general symptom regardless of the intensity grade or relationship to vaccination. This outcome measure was only assessed in subjects from Sub-cohort 1, who received the EPI vaccination independently of study vaccination with the Rotarix™ vaccine/placebo.

  • Number of Subjects With Any Solicited General Symptoms Following Administration of the Co-administered EPI Vaccines [ Time Frame: 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 ] [ Designated as safety issue: No ]
    Solicited general symptoms assessed following administration of the co-administered EPI vaccines were drowsiness, gastrointestinal symptoms, fussiness/irritability, loss of appetite, and fever, defined as axillary temperature (T) above or equal to [>=] 37.5 degrees Celsius [°C] (if GSK scale) or >= 37.1°C (if Chinese scale ). Any = any occurrence of the specified solicited general symptom regardless of the intensity grade or relationship to vaccination. This outcome measure was only assessed in subjects from Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix™ vaccine/placebo.

  • Number of Subjects With Any Solicited Local Symptoms Following Dose 2 of the Rotarix™ Vaccine/Placebo [ Time Frame: Within the 8-day (Days 0-7) follow-up periods following Dose 2 of the Rotarix™ vaccine/placebo ] [ Designated as safety issue: No ]
    Solicited local symptoms assessed following administration of the co-administered EPI vaccines were pain, swelling, and redness. Any = any occurrence of the specified solicited local symptom regardless of the intensity grade. This outcome measure was only assessed in subjects from Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix™ vaccine/placebo.

  • Number of Subjects With Any Unsolicited Adverse Events (AEs) [ Time Frame: Within the 31-day (Days 0-30) follow-up periods following any dose of the Rotarix™ vaccine or placebo ] [ Designated as safety issue: No ]
    An unsolicited AE is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any = occurrence of an unsolicited AE regardless of the intensity grade or relationship to vaccination.

  • Number of Subjects With Any Serious Adverse Events (SAEs) [ Time Frame: Throughout the entire study period (from Day 0 to Study End at Month 21) ] [ Designated as safety issue: No ]
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, or result in disability/incapacity. Any = occurrence of an SAE regardless of the intensity grade or relationship to vaccination.

  • Number of Seroconverted Subjects for Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibodies [ Time Frame: At Month 2 and at 12 months of age ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a subject seronegative at baseline (Day 0) with the appearance of anti-RV IgA antibody concentration greater than or equal to (≥) 20 units per milliliter (U/mL) at the time point assessed. A seronegative subject was defined as a subject with anti-RV IgA antibody concentration lower than (<) 20 U/mL.

  • Number of Seroconverted Subjects for Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibodies. [ Time Frame: At Month 2 and at 12 months of age ] [ Designated as safety issue: No ]
    A seroconverted subject was defined as a subject seronegative at baseline (Day 0) with the appearance of anti-RV IgA antibody concentration greater than or equal to (≥) 20 units per milliliter (U/mL) at the time point assessed. A seronegative subject was defined as a subject with anti-RV IgA antibody concentration lower than (<) 20 U/mL.

  • Number of Subjects Seropositive for Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibodies. [ Time Frame: At Day 0, Month 2 and at 12 months of age ] [ Designated as safety issue: No ]
    A subject seropositive for anti-rotavirus (anti-RV) immunoglobulin A (IgA) antibodies was defined as a subject anti-RV IgA antibody concentration greater than or equal to (≥) the seropositivity cut-off of 20 units per milliliter (U/mL).

  • Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations [ Time Frame: At Day 0, Month 2 and at 12 months of age ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs), in units per milliliter (U/mL). The cut-off of the assay was the seropositivity cut-off (≥ 20 U/mL).

  • Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations. [ Time Frame: At Day 0, Month 2 and at 12 months of age. ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs), in units per milliliter (U/mL). The cut-off of the assay was the seropositivity cut-off (≥ 20 U/mL).

  • Anti-rotavirus (Anti-RV) Immunoglobulin A (IgA) Antibody Concentrations. [ Time Frame: At Day 0, Month 2 and at 12 months of age ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs), in units per milliliter (U/mL). The cut-off of the assay was the seropositivity cut-off (≥ 20 U/mL).

  • Number of Subjects Seroprotected Against Diphtheria and Tetanus [ Time Frame: At Day 0 and at Month 4 ] [ Designated as safety issue: No ]
    A subject seroprotected against diphtheria/tetanus was defined as a subject with an anti-diphtheria (anti-D)/anti-tetanus (anti-T) antibody concentrations greater than or equal to (≥) 0.1 international units per milliliter (IU/mL). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix™ vaccine/placebo

  • Anti-Diphtheria (Anti-D) and Anti-tetanus (Anti-T) Antibody Concentrations [ Time Frame: At Day 0 and at Month 4 ] [ Designated as safety issue: No ]
    Concentrations were expressed as geometric mean concentrations (GMCs) in international unit per milliliter (IU/mL). The cut-off of the assay was the seroprotection cut-off assay (≥ 0.1 IU/mL). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix™ vaccine/placebo.

  • Number of Subjects Seroprotected Against Poliovirus Types 1, 2 and 3. [ Time Frame: At Day 0 and at Month 4 ] [ Designated as safety issue: No ]
    A subject seroprotected against poliovirus types 1, 2 and 3 was defined as a subject with anti-poliovirus type 1 (anti-polio 1)/anti-polio 2/anti-polio 3 antibody titer greater than or equal to (≥) 8 estimated doses 50% (ED50). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix™ vaccine/placebo (cf. population definition below).

  • Titers for Anti-poliovirus Type 1 (Anti-polio 1), Anti-polio 2 and Anti-polio 3 Antibodies [ Time Frame: At Day 0 and at Month 4 ] [ Designated as safety issue: No ]
    Titers were expressed as geometric mean titers (GMTs). The cut-off of the assay was the seroprotection cut-off (≥ 8 estimated doses 50% [ED50] for anti-poliovirus type 1 [anti-polio 1]/anti-polio 2/anti-polio 3 antibodies. This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix™ vaccine/placebo.

  • Number of Subjects Seropositive for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin (Anti-FHA) and Anti-pertactin (Anti-PRN) Antibodies. [ Time Frame: At Day 0 and at Month 4 ] [ Designated as safety issue: No ]
    Antibody assessment was performed by enzyme-linked immunosorbent assay (ELISA). A subject seropositive for anti-PT/anti-FHA/anti-PRN antibodies was defined as a subject with an anti-PT/anti-FHA/anti-PRN antibody concentrations greater than or equal to (≥) 5 ELISA units per milliliter (EL.U/mL). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix™ vaccine/placebo.

  • Concentrations for Anti-pertussis Toxoid (Anti-PT), Anti-filamentous Haemagglutinin [ Time Frame: At Day 0 and at Month 4 ] [ Designated as safety issue: No ]
    Antibody assessment was performed by enzyme-linked immunosorbent assay (ELISA). Concentrations were expressed as geometric mean concentrations (GMCs) in ELISA units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off (≥ 5 EL.U/mL) for all antibodies assessed (anti-PT, anti-FHA and anti-PRN). This outcome measure concerns solely subjects in Sub-cohort 2, who received the EPI vaccination concomitantly with study vaccination with the Rotarix™ vaccine/placebo.


Enrollment: 3340
Study Start Date: August 2010
Study Completion Date: May 2012
Primary Completion Date: May 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Biological: GSK Biologicals' liquid human rotavirus vaccine 444563
Oral administration
Biological: Infanrix™
Intramuscular administration
Other Name: DTPa
Biological: Institute of Medical Biology Chinese Academy of Medical Sciences' Oral poliovirus vaccine (OPV)
Oral administration
Placebo Comparator: 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.
Biological: Placebo
Oral administration
Biological: Infanrix™
Intramuscular administration
Other Name: DTPa
Biological: Institute of Medical Biology Chinese Academy of Medical Sciences' Oral poliovirus vaccine (OPV)
Oral administration

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.

  Eligibility

Ages Eligible for Study:   6 Weeks to 16 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01171963

Locations
China, Guangxi
GSK Investigational Site
Hechi, Guangxi, China, 547000
GSK Investigational Site
Liucheng County, Guangxi, China, 545200
GSK Investigational Site
Liuzhou, Guangxi, China, 545100
GSK Investigational Site
Luzhai County, Guangxi, China, 545600
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided by GlaxoSmithKline

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01171963     History of Changes
Other Study ID Numbers: 113808
Study First Received: July 28, 2010
Results First Received: May 2, 2013
Last Updated: December 19, 2013
Health Authority: China: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
Liquid human retrovirus vaccine

Additional relevant MeSH terms:
Rotavirus Infections
RNA Virus Infections
Reoviridae Infections
Virus Diseases

ClinicalTrials.gov processed this record on November 25, 2014