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

NCT00241644 | Completed Phase 3 Results

• 1 other identifier: 102248
• Study Type: interventional
• Target: 2,089
• Locations: 2 countries
• Sites: 13

Brief Summary

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.

Conditions

Infections, Rotavirus

Keywords

Rotavirus gastroenteritis; HRV vaccine

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (18)

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

  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

  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

  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

  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

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

Study Arms (3)

Rotarix 3-Dose Group

EXPERIMENTAL

Subjects received 3 doses of Rotarix™ vaccine given concomitantly with routine EPI vaccines.

Biological: Rotarix™

Rotarix 2-Dose Group

EXPERIMENTAL

Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ vaccine given concomitantly with routine EPI vaccines.

Biological: Rotarix™; Biological: Placebo

Placebo Group

PLACEBO COMPARATOR

Subjects received 3 doses of placebo given concomitantly with routine EPI vaccines.

Biological: Placebo

Interventions

Rotarix™ BIOLOGICAL

Two or Three doses, oral administration

Also known as: GSK Biologicals' HRV vaccine

Rotarix 2-Dose Group; Rotarix 3-Dose Group

Placebo BIOLOGICAL

One or three doses, oral administration.

Placebo Group; Rotarix 2-Dose Group

Eligibility Criteria

• Age: 5 Weeks - 10 Weeks
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (13)

GSK Investigational Site

Bangwe, Blantyre, 3, Malawi

Location

GSK Investigational Site

Limbe, Blantyre, 3, Malawi

Location

GSK Investigational Site

Ndirande, Blantyre, 3, Malawi

Location

GSK Investigational Site

Zingwanga, Blantyre, 3, Malawi

Location

GSK Investigational Site

Brits, 0250, South Africa

Location

GSK Investigational Site

Diepkloof, Soweto, South Africa

Location

GSK Investigational Site

Diepsloot, South Africa

Location

GSK Investigational Site

Eldorado Park Ext 9, Soweto, South Africa

Location

GSK Investigational Site

Karenpark, 0118, South Africa

Location

GSK Investigational Site

Mamelodi, South Africa

Location

GSK Investigational Site

Mamelodi East, South Africa

Location

GSK Investigational Site

Shoshanguve, South Africa

Location

GSK Investigational Site

Tembisa, South Africa

Location

Related Publications (14)

• Cunliffe N et al. Efficacy of human rotavirus vaccine RIX4414 in Africa during the first year of life. Abstract presented at the 27th Annual Meeting of the European Society for Paediatric Infectious Disease (ESPID), Brussels, Belgium, 9-13 June 2009.

  BACKGROUND

• Cunliffe NA, Witte D, Ngwira BM, Todd S, Bostock NJ, Turner AM, Chimpeni P, Victor JC, Steele AD, Bouckenooghe A, Neuzil KM. Efficacy of human rotavirus vaccine against severe gastroenteritis in Malawian children in the first two years of life: a randomized, double-blind, placebo controlled trial. Vaccine. 2012 Apr 27;30 Suppl 1(0 1):A36-43. doi: 10.1016/j.vaccine.2011.09.120.

  PMID: 22520135 BACKGROUND

• Cunliffe NA et al. Efficacy of Human Rotavirus Vaccine RIX4414 in Malawian Infants in the first two years of life. Abstract presented at the 6th African Rotavirus Symposium, Johannesburg, South Africa, 2-3 August 2010.

  BACKGROUND

• Madhi SA, Cunliffe NA, Steele D, Witte D, Kirsten M, Louw C, Ngwira B, Victor JC, Gillard PH, Cheuvart BB, Han HH, Neuzil KM. Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med. 2010 Jan 28;362(4):289-98. doi: 10.1056/NEJMoa0904797.

  PMID: 20107214 BACKGROUND

• Madhi S et al. Efficacy of the human rotavirus vaccine RIX4414 against rotavirus G2P[4]/g8p[4] strains in South African infants. Abstract presented at the 6th world congress of the World Society for Pediatric Infectious Diseases (WSPID), Buenos Aires, Argentina, 18-22 November 2009.

  BACKGROUND

• Madhi SA, Kirsten M, Louw C, Bos P, Aspinall S, Bouckenooghe A, Neuzil KM, Steele AD. Efficacy and immunogenicity of two or three dose rotavirus-vaccine regimen in South African children over two consecutive rotavirus-seasons: a randomized, double-blind, placebo-controlled trial. Vaccine. 2012 Apr 27;30 Suppl 1:A44-51. doi: 10.1016/j.vaccine.2011.08.080.

  PMID: 22520136 BACKGROUND

• Nakagomi T, Nakagomi O, Dove W, Doan YH, Witte D, Ngwira B, Todd S, Duncan Steele A, Neuzil KM, Cunliffe NA. Molecular characterization of rotavirus strains detected during a clinical trial of a human rotavirus vaccine in Blantyre, Malawi. Vaccine. 2012 Apr 27;30 Suppl 1(0 1):A140-51. doi: 10.1016/j.vaccine.2011.09.119.

  PMID: 22520123 BACKGROUND

• Neuzil K et al. Immunogenicity of human rotavirus vaccine RIX4414 in South African and Malawian infants. Abstract presented at the 6th world congress of the World Society for Pediatric Infectious Diseases (WSPID), Buenos Aires, Argentina, 18-22 November 2009.

  BACKGROUND

• Neuzil K et al. RIX4414 is protective against severe RVGE caused by diverse rotavirus serotypes during the first year of life in African infants. Abstract presented at the 27th Annual Meeting of the European Society for Paediatric Infectious Disease (ESPID), Brussels, Belgium, 9-13 June 2009.

  BACKGROUND

• Steele AD et al. Efficacy of human rotavirus vaccine, Rotarix™ against severe gastroenteritis caused by diverse circulating rotavirus strains in African infants. Abstract presented at the 7th World Congress for World Society for Pediatric Infectious Diseases (WSPID). Melbourne, Australia, 16-19 November 2011.

  BACKGROUND

• Steele D et al. Diverse circulating rotavirus strains during the first year of life in African infants. Abstract presented at 10th International symposium on dsRNA Viruses, Hamilton Island, QLD, Australia, 21-25 June 2009.

  BACKGROUND

• Gruber JF, Becker-Dreps S, Hudgens MG, Brookhart MA, Thomas JC, Jonsson Funk M. Timing and predictors of severe rotavirus gastroenteritis among unvaccinated infants in low- and middle-income countries. Epidemiol Infect. 2018 Apr;146(6):698-704. doi: 10.1017/S0950268818000626. Epub 2018 Mar 22.

  PMID: 29564996 DERIVED

• Madhi SA, Cunliffe NA, Steele D, Witte D, Kirsten M, Louw C, Ngwira B, Victor JC, Gillard PH, Cheuvart BB, Han HH, Neuzil KM. Effect of human rotavirus vaccine on severe diarrhea in African infants. Malawi Med J. 2016 Sep;28(3):108-114.

  PMID: 27895844 DERIVED

• Steele AD, Neuzil KM, Cunliffe NA, Madhi SA, Bos P, Ngwira B, Witte D, Todd S, Louw C, Kirsten M, Aspinall S, Van Doorn LJ, Bouckenooghe A, Suryakiran PV, Han HH. Human rotavirus vaccine Rotarix provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial. BMC Infect Dis. 2012 Sep 13;12:213. doi: 10.1186/1471-2334-12-213.

  PMID: 22974466 DERIVED

Related 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.

MeSH Terms

Conditions

Rotavirus Infections

Interventions

RIX4414 vaccine

Condition Hierarchy (Ancestors)

Reoviridae Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2005
• First Posted: October 19, 2005
• Study Start: October 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: December 9, 2016
• Results First Posted: August 4, 2009

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will share

Locations

ZA (9); MA (4)