A Study to Test 2 Doses of the HRV Vaccine in Healthy Infants.

Infections, Rotavirus Clinical Trial

Official title:

A Placebo-controlled, Multi-country & Multi-center Study to Assess the Efficacy, Safety & Immunogenicity of 2 Doses of GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine in Healthy Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00140673
• Other study ID #: 444563/023
• Status: Completed
• Phase: Phase 3
• Start date: August 5, 2003
• Est. completion date: October 20, 2005

Study information

• Verified date: December 2019
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The main objectives of this study are: 1) In a subset (N = 20 000), to determine vaccine efficacy against severe rotavirus (RV) gastroenteritis (GE) during the period starting from 2 weeks after Dose 2 until one year of age. 2) In all subjects (N = 60 000), to determine the safety of GSK Biologicals' HRV vaccine with respect to definite intussusception (IS) within 31 days (Day 0-Day 30) after each HRV vaccine dose.

Description:

The study has two groups: Group HRV and Group Placebo. Two oral doses administered to healthy infants who are 6-13 weeks of age at the time of Dose 1, according to a 0, 1 to 2-month schedule. Routine EPI vaccinations are given at the discretion of the investigator and according to local National Plans of Immunisation schedule in each participating country. A minimum 2-week interval was to be observed between HRV vaccine and OPV doses. Of the total enrolled cohort of 60 000 subjects, 20 000 subjects were followed for efficacy and safety until one year of age while 40 000 subjects were followed for safety only until 30-90 days after the second HRV/placebo dose. A subset (N = approximately 13 000) of the 20 000 subjects are followed for efficacy and safety until 24 months of age. From the 20 000 subjects followed for efficacy and safety, a subset of 100 subjects per country (center specific, except Finland) provided two blood sample to evaluate immunogenicity.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 63227
• Est. completion date: October 20, 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Weeks to 13 Weeks

Eligibility

Inclusion criteria:

• Healthy infants 6-13 weeks of age at the time of the first study vaccination whose parent/guardian sign a written informed consent and whose parents/guardians can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits)

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 since birth. (Topical steroids are allowed.)

• Child is unlikely to remain in the study area for the duration of the study

• Any confirmed or suspected immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection

• History of allergic disease or reaction likely to be exacerbated by any component of the vaccine

• Administration of immunoglobulins and/or blood products since birth or planned administration during the study period

• Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the gastrointestinal tract or other serious medical condition as determined by the investigator

Related Conditions & MeSH terms

• Infections, Rotavirus
• Rotavirus Infections

Intervention

Biological:
• Rotavirus

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Villanueva	Mendoza
Brazil	GSK Investigational Site	Belem	Pará
Chile	GSK Investigational Site	Concepción	Región Del Biobio
Chile	GSK Investigational Site	Valparaiso	Valparaíso
Colombia	GSK Investigational Site	Cali Colombia
Dominican Republic	GSK Investigational Site	Santo Domingo
Finland	GSK Investigational Site	Tampere
Honduras	GSK Investigational Site	Tegucigalpa
Mexico	GSK Investigational Site	Cuernavaca
Mexico	GSK Investigational Site	Durango
Mexico	GSK Investigational Site	Mexico
Mexico	GSK Investigational Site	Mexico DF
Mexico	GSK Investigational Site	Tlanepantla
Nicaragua	GSK Investigational Site	Leon
Panama	GSK Investigational Site	Panama
Peru	GSK Investigational Site	Lima
Venezuela	GSK Investigational Site	Valencia	Carabobo

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

Argentina,  Brazil,  Chile,  Colombia,  Dominican Republic,  Finland,  Honduras,  Mexico,  Nicaragua,  Panama,  Peru,  Venezuela, 

References & Publications (13)

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. — View Citation

Costa Clemens SA et al. Operational organization of a large scale phase III clinical trial of rotavirus vaccine in multiple sites and countries in Latin America. Poster presented at ICP, Cancun, Mexico, 15-20 August 2004.

De Vos B et al. Rotarix™: an effective way to prevent rotavirus diarrhoea and vomiting. Proc. 9th Congress of the Asian Pan Pacific Society of Paediatric Gastroenterology, Hepatology and Nutrition & 27th Annual Congress of the Malaysian Paediatric Association, Kuala Lumpur, 16-19 June 2005.

De Vos B, Han HH, Bouckenooghe A, Debrus S, Gillard P, Ward R, Cheuvart B. Live attenuated human rotavirus vaccine, RIX4414, provides clinical protection in infants against rotavirus strains with and without shared G and P genotypes: integrated analysis of randomized controlled trials. Pediatr Infect Dis J. 2009 Apr;28(4):261-6. doi: 10.1097/INF.0b013e3181907177. — View Citation

Han HH, Karkada N, Jayadeva G, Dubin G. Serologic response to porcine circovirus type 1 (PCV1) in infants vaccinated with the human rotavirus vaccine, Rotarix™: A retrospective laboratory analysis. Hum Vaccin Immunother. 2017 Jan 2;13(1):237-244. doi: 10.1080/21645515.2016.1231262. — View Citation

Justino MC, Araújo EC, van Doorn LJ, Oliveira CS, Gabbay YB, Mascarenhas JD, Miranda YS, Guerra Sde F, Silva VB, Linhares AC. Oral live attenuated human rotavirus vaccine (Rotarix™) offers sustained high protection against severe G9P[8] rotavirus gastroenteritis during the first two years of life in Brazilian children. Mem Inst Oswaldo Cruz. 2012 Nov;107(7):846-53. — View Citation

Linhares AC, Velázquez FR, Pérez-Schael I, Sáez-Llorens X, Abate H, Espinoza F, López P, Macías-Parra M, Ortega-Barría E, Rivera-Medina DM, Rivera L, Pavía-Ruz N, Nuñez E, Damaso S, Ruiz-Palacios GM, De Vos B, O'Ryan M, Gillard P, Bouckenooghe A; Human Rotavirus Vaccine Study Group. Efficacy and safety of an oral live attenuated human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in Latin American infants: a randomised, double-blind, placebo-controlled phase III study. Lancet. 2008 Apr 5;371(9619):1181-9. doi: 10.1016/S0140-6736(08)60524-3. — View Citation

Macias M et al. The rotavirus vaccine RIX4414 (Rotarix) is not associated with intussusception in one year old infants. Proc. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), Washington DC, USA, 16-19 December 2005.

O'Ryan et al. A novel rotavirus vaccine RIX4414 is not associated with intussusception. Proc. 44th ICAAC, Washington DC, USA, October 30-November 2, 2004.

Ruiz-Palacios GM, Pérez-Schael I, Velázquez FR, Abate H, Breuer T, Clemens SC, Cheuvart B, Espinoza F, Gillard P, Innis BL, Cervantes Y, Linhares AC, López P, Macías-Parra M, Ortega-Barría E, Richardson V, Rivera-Medina DM, Rivera L, Salinas B, Pavía-Ruz N, Salmerón J, Rüttimann R, Tinoco JC, Rubio P, Nuñez E, Guerrero ML, Yarzábal JP, Damaso S, Tornieporth N, Sáez-Llorens X, Vergara RF, Vesikari T, Bouckenooghe A, Clemens R, De Vos B, O'Ryan M; Human Rotavirus Vaccine Study Group. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. 2006 Jan 5;354(1):11-22. — View Citation

Vesikari et al. High efficacy of two doses of Rotarix™ (RIX4414) against rotavirus disease in Europe, Latin-America and Asia. Presented at ACPID, Cebu, Philippines, 7-10 March 2006.

Vesikari T et al. Overcoming the safety hurdle: the rotavirus vaccine RIX4414 is not associated with intussusception. 23rd Annual Meeting of European Society for Paediatric Infectious Diseases, Valencia, Spain, 18-20 May 2005.

Vesikari T et al. RIX4414: A new attenuated human rotavirus vaccine. 23rd Annual Meeting of European Society for Paediatric Infectious Diseases, Valencia, Spain, 18-20 May 2005.

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	1. Occurrence of severe RV GE caused by the wild RV strains during the period starting from 2 weeks after Dose 2 until one year of age. 2. Occurrence of definite IS cases within 31 days (Day 0 -Day 30) after each HRV vaccination dose.
Secondary	Severe RV GE by wild-type G1, non-G1, each non-G1, 11 score after Dose 2 and Dose 1 until 1-year old.
Secondary	Severe RV GE in subset during the 2nd year and both years.
Secondary	SAEs.
Secondary	Definite IS until 1-year old and 2-years old.
Secondary	Serum anti-RV IgA at Visits 1 and 3 (subset/country except Finland).

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