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

Efficacy, Safety, Reactogenicity and Immunogenicity Study of the Lyophilised Formulation of Rotarix Vaccine in Healthy Japanese Infants

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.

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 765
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Aichi, Japan, 451-0052
    • GSK Investigational Site
  • Chiba, Japan, 275-8580
    • GSK Investigational Site
  • Fukuoka, Japan, 802-8533
    • GSK Investigational Site
  • Hiroshima, Japan, 720-8520
    • GSK Investigational Site
  • Hiroshima, Japan, 734-8530
    • GSK Investigational Site
  • Hiroshima, Japan, 737-0811
    • GSK Investigational Site
  • Hiroshima, Japan, 730-8518
    • GSK Investigational Site
  • Hiroshima, Japan, 730-8798
    • GSK Investigational Site
  • Hokkaido, Japan, 065-0033
    • GSK Investigational Site
  • Hokkaido, Japan, 003-0021
    • GSK Investigational Site
  • Kagawa, Japan, 765-8501
    • GSK Investigational Site
  • Kanagawa, Japan, 247-8533
    • GSK Investigational Site
  • Miyagi, Japan, 983-8520
    • GSK Investigational Site
  • Miyagi, Japan, 981-3203
    • GSK Investigational Site
  • Nagano, Japan, 386-8610
    • GSK Investigational Site
  • Nagasaki, Japan, 856-8562
    • GSK Investigational Site
  • Niigata, Japan, 957-8588
    • GSK Investigational Site
  • Okayama, Japan, 701-1192
    • GSK Investigational Site
  • Okayama, Japan, 701-0204
    • GSK Investigational Site
  • Osaka, Japan, 591-8025
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 3 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Buyse H, Vinals C, Karkada N, Han HH. The human rotavirus vaccine Rotarix in infants: an integrated analysis of safety and reactogenicity. Hum Vaccin Immunother. 2014;10(1):19-24. doi: 10.4161/hv.26476. Epub 2013 Oct 8.
• Kawamura N, Tokoeda Y, Oshima M, Okahata H, Tsutsumi H, Van Doorn LJ, Muto H, Smolenov I, Suryakiran PV, Han HH. Efficacy, safety and immunogenicity of RIX4414 in Japanese infants during the first two years of life. Vaccine. 2011 Aug 26;29(37):6335-41. doi: 10.1016/j.vaccine.2011.05.017. Epub 2011 Jun 2.
• Kawamura N et al. Efficacy of Human Rotavirus (G1P[8] strain) Vaccine (HRV) RIX4414 in Japanese Infants during the Two-year Efficacy Follow-up Period. Abstract presented at the 114th Annual Meeting of Japan Pediatric Society (JPS). Tokyo, Japan, 12-14 August 2011.
• Kawamura N et al. Efficacy of human rotavirus vaccine RIX4414 in Japanese infants from 2 weeks post dose 2 up to data lock point. Abstract presented at the 28th meeting of European Society for Paediatric Infectious Diseases (ESPID). Nice, France, 4-8 May 2010.
• Bergman H, Henschke N, Hungerford D, Pitan F, Ndwandwe D, Cunliffe N, Soares-Weiser K. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database Syst Rev. 2021 Nov 17;11(11):CD008521. doi: 10.1002/14651858.CD008521.pub6.

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): June 19, 2007
• Primary Completion (Actual): March 31, 2009
• Study Completion (Actual): November 21, 2009

Study Registration Dates

• First Submitted: May 29, 2007
• First Submitted That Met QC Criteria: May 29, 2007
• First Posted (Estimate): May 30, 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

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Reoviridae Infections; Rotavirus Infections
• Other Study ID Numbers: 107625; 2015-001543-36 (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: 107625
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Statistical Analysis Plan
   Information identifier: 107625
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Individual Participant Data Set
   Information identifier: 107625
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Study Protocol
   Information identifier: 107625
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 107625
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Annotated Case Report Form
   Information identifier: 107625
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Clinical Study Report
   Information identifier: 107625
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register