Assess the Immunogenicity of the Human Rotavirus (HRV) Vaccine After Reconstitution Without Buffering Agent; & Evaluate the Immunogenicity, Reactogenicity & Safety of the Vaccine After Storage for 7 d at 37°C Following 2 Doses in Healthy Infants

A Phase IIIb, Partially Blind, Randomized, Placebo-controlled Study to Asses the Effect on Immunogenicity of Administration of Vaccine Without Buffering Agent and to Assess Heat Stability in Terms of Immunogenicity, Reactogenicity and Safety of GlaxoSmithKline Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine Following a 0, 2 Month Schedule, in Healthy Infants Previously Uninfected With Human Rotavirus

Rotavirus (RV) is the most important cause of acute gastroenteritis (GE) requiring hospitalization of infants and young children in developed and developing countries and can be a frequent cause of death in children less than 5 years of age. GSK Biologicals has developed a vaccine against human rotavirus gastroenteritis. In this study, the immunogenicity, reactogenicity and safety of the HRV vaccine will be evaluated when stored or reconstituted in circumstances different from the recommendations: i.e. when not reconstituted with a buffer or when stored for 7 days at 37°C before reconstitution. In addition, the effect of feeding will be explored for HRV vaccine reconstituted without buffer.

Study Overview

• Status: Completed
• Conditions: Rotavirus Gastroenteritis
• Intervention / Treatment: Biological: Live attenuated human rotavirus vaccine

Detailed Description

Assess the effect on immunogenicity of administration of vaccine without buffering agent & assess heat stability in terms of immunogenicity, reactogenicity & safety of GSK Biologicals' oral live attenuated human rotavirus (HRV) vaccine following a 0,2 m schedule, in healthy infants previously uninfected with human rotavirus

• Study Type: Interventional
• Enrollment (Actual): 450
• Phase: Phase 3

Contacts and Locations

Study Locations

• Thailand
  • Bangkok, Thailand, 10400
    • GSK Investigational Site
  • Bangkok, Thailand, 10700
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 month to 2 months (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

INCLUSION CRITERIA:

• A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination.
• Written informed consent obtained from the parent or guardian of the subject.
• Free of obvious health problems as established by medical history and clinical examination before entering into the study.

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 placebo, or planned use during the study period.
• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs prior to the first vaccine dose, since birth. (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
• Planned administration of a vaccine (except routine paediatric vaccines) not foreseen by the study protocol. (If exceptionally OPV is given, this should be administered at least 14 days apart from the HRV vaccine or placebo dose.)
• Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the GI tract or other serious medical condition as determined by the investigator.
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
• Any confirmed or suspected immunosuppressive or immunodeficient condition based on medical history and physical examination (no laboratory testing is required).
• Major congenital defects or serious chronic illness.
• Gastroenteritis within 7 days preceding the study vaccine administration (warrants deferral of the vaccination).
• Administration of immunoglobulins and/or blood products since birth or planned administration during the study period. Oral intake of immunoglobulins via e.g. breastfeeding is allowed.
• Previous confirmed occurrence of RV gastroenteritis.

Study Plan

How is the study designed?

Design Details

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects with vaccine take	At 2 months post-Dose 2

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of subjects who seroconverted (percentage of subjects with concentrations ≥ 20 U/mL in subjects who were negative for rotavirus (RV) before vaccination)	At 2 months post-Dose 2
Evaluation of the serum anti-RV IgA (immunoglobulin A) antibody concentrations expressed as Geometric Mean Concentrations (GMC)	At 2 months post-Dose 2
Rotavirus antigen shedding in planned stool samples	At Day 0, Day 7 and Day 15 post each study vaccine dose
Presence of RV in gastroenteritis (GE) episode stools collected	From Dose 1 of HRV vaccine/placebo up to 2 months post-Dose 2
For each type of solicited symptoms, occurrence of the symptom	Within the 15-day (Day 0-14) solicited follow-up period after each study vaccine dose
Occurrence of any Grade 2 or Grade 3 fever, vomiting or diarrhea	Within the 15-day (Day 0-14) solicited follow-up period after each study vaccine dose
Occurrence of unsolicited adverse events (AEs) according to Medical Dictionary for Regulatory Activities (MedDRA) classification	Within 31 days (Day 0-30) after each study vaccine dose
Occurrence of serious adverse events (SAEs) according to MedDRA classification	Throughout the study period (Day 0 to Month 4)

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

General Publications

• Kerdpanich A, Chokephaibulkit K, Watanaveeradej V, Vanprapar N, Simasathien S, Phavichitr N, Bock HL, Damaso S, Hutagalung Y, Han HH. Immunogenicity of a live-attenuated human rotavirus RIX4414 vaccine with or without buffering agent. Hum Vaccin. 2010 Mar 26;6(3):10428. doi: 10.4161/hv.6.3.10428. Epub 2010 Mar 26.
• Chokephaibulkit K et al. Immunogenicity And Vaccine Take Of RIX4414 (Rotarix") After Heat Exposure. Abstract presented at the 5th World Congress of the World Society for Pediatric infectious Diseases (WSPID). Bangkok, Thailand, 15-18 November 2007.
• Debrus S et al. Study of the viral activity of RIX4414 - human rotavirus vaccine. Abstract presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Chicago, USA, 17-20 September 2007.
• Debrus S et al. Viral shedding (methodology). Abstract presented at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). Chicago, USA, 17-20 September 2007.
• Kerdpanich A et al. Feeding does not influence the immunogenicity of RIX4414 (Rotarix") in Thailand. Abstract presented at the 5th World Congress of the World Society for Pediatric infectious Diseases ( WSPID). Bangkok, Thailand, 15-18 November 2007.
• Kerdpanich et al. Exposure to elevated temperature of 37°C for 7 days does not affect immunogenicity and reactogenicity of RIX4414. Abstract presented at the 9th dsRNA Virus Meeting. Cape Town, South Africa, 21-26 October 2006.
• Kerdpanich A, Chokephaibulkit K, Watanaveeradej V, Vanprapar N, Simasathien S, Phavichitr N, Bock HL, Damaso S, Hutagalung Y, Han HH. Immunogenicity of a human rotavirus vaccine (RIX4414) after storage at 37 degrees C for seven days. Hum Vaccin. 2011 Jan 1;7(1):74-80. doi: 10.4161/hv.7.1.13412. Epub 2011 Jan 1.

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: March 1, 2005
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: September 9, 2005
• First Submitted That Met QC Criteria: September 9, 2005
• First Posted (Estimate): September 15, 2005

Study Record Updates

• Last Update Posted (Estimate): January 16, 2017
• Last Update Submitted That Met QC Criteria: January 13, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Gastroenteritis
• Other Study ID Numbers: 103477 (Other Identifier: GSK)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Dataset Specification
   Information identifier: 103477
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Study Protocol
   Information identifier: 103477
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Statistical Analysis Plan
   Information identifier: 103477
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Informed Consent Form
   Information identifier: 103477
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: 103477
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: 103477
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register