Clinical trial NCT00140686: To Test 2 Doses of GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine in Healthy Infants in Co-administration With Specific Childhood Vaccines
Official title: A 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 in Co-administration With Specific Childhood Vaccines
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Infections, Rotavirus
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2005-09-01
Enrollment: 3994
Sex: ALL
Minimum age (years): 6
Maximum age (years): 14
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The main objectives of this study is to determine vaccine efficacy against any rotavirus (RV) gastroenteritis (GE) during the first efficacy period.

Detailed description: The study has two groups: Group HRV and Group Placebo. Two oral doses administered to healthy infants who are 6-14 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.

Eligibility criteria: Inclusion criteria:

* Healthy infants 6 -14 weeks of age at the time of the first study vaccination with birth weight \> 2000g 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 planned use during the study period.
* 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. (Topical steroids are allowed.)
* History of diphtheria, tetanus, pertussis, Hib disease and/ or hepatitis B disease (in all subjects). Only for subjects in Spain: history of meningococcal group C disease. Only for subjects in France and Germany: history of disease caused by Streptococcus pneumoniae.
* History of use of experimental rotavirus vaccine.
* Previous vaccination against diphtheria, tetanus, pertussis, Haemophilus influenzae type b (in all subjects). Only for subjects in Spain: previous vaccination against meningococcal group C. Only for subjects in France and Germany: previous vaccination against Streptococcus pneumoniae.
* Any clinically significant history of chronic gastrointestinal disease including any uncorrected congenital malformation of the GI tract, IS 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 (no laboratory testing is required).
* History of allergic disease or reaction likely to be exacerbated by any component of the vaccine.
* Acute disease at the time of enrolment. (Acute disease is defined as the presence of a moderate or severe illness with or without fever. All vaccines can be administered to persons with a minor illness such as mild upper respiratory infection with or without low-grade febrile illness, i.e. Oral temperature \<37.5°C (99.5°F) / Axillary temperature \<37.5°C (99.5°F) / Rectal temperature \<38°C (100.4°F).)
* Gastroenteritis within 7 days preceding the first study vaccine administration (warrants deferral of the vaccination).
* 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.
* Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.

Primary outcomes:
measure: Occurrence of any RV GE caused by the circulating wild-type RV strains during the first efficacy follow-up period.
Secondary outcomes:
measure: Occurrence of severe RV GE caused by the circulating wild-type RV strains during the each efficacy follow-up period.
measure: Occurrence of any and severe RV GE caused by the circulating wild-type RV strains of G1 serotype during each efficacy follow-up period.
measure: Occurrence of any and severe RV GE caused by the circulating wild-type RV strains of non-G1 serotypes during each efficacy follow-up period.
measure: Occurrence of hospitalization due to RV GE caused by the circulating wild-type RV strains during each efficacy follow-up period.
measure: Occurrence of any medical attention (medical provider contact, advice, visit; emergency room contact or visit or hospitalization) for RV GE caused by the circulating wild-type RV strains during each efficacy follow-up period.
measure: Occurrence of any and severe RV GE caused by the circulating wild-type RV strains during the period starting from Dose 1 of the study vaccine until Visit 5.
measure: Occurrence of any and severe RV GE caused by the circulating wild-type RV strains during the first efficacy follow-up period in subjects who completed the two-dose vaccination course before the RV epidemic season.
measure: Occurrence of any and severe RV GE caused by the circulating wild-type RV strains during the first efficacy follow-up period in subjects who were vaccinated during the RV epidemic season.
measure: Immune response to HRV vaccine at Visit 1 and Visit 3.
measure: Immune response to all antigens contained in each of the different childhood vaccines at Visit 3 and Visit 4 or Visit 6 (if applicable):
measure: In a subset of subjects (N=1800), occurrence of each type of solicited symptom within the 8-day solicited follow-up period (Day 0 to Day 7) after each dose of HRV/placebo.
measure: For all subjects, occurrence of unsolicited symptoms within 31 days (Day 0 to Day 30) after each dose of HRV/placebo and SAEs throughout the entire study period.
Other outcomes:
Locations:
city: Brno
country: Czech Republic
facility: GSK Investigational Site
city: Havlickuv Brod
country: Czech Republic
facility: GSK Investigational Site
city: Hradec kralove
country: Czech Republic
facility: GSK Investigational Site
city: Humpolec
country: Czech Republic
facility: GSK Investigational Site
city: Jindrichuv Hradec
country: Czech Republic
facility: GSK Investigational Site
city: Nachod
country: Czech Republic
facility: GSK Investigational Site
city: Ostrava
country: Czech Republic
facility: GSK Investigational Site
city: Pardubice
country: Czech Republic
facility: GSK Investigational Site
city: Praha 4
country: Czech Republic
facility: GSK Investigational Site
city: Praha 5
country: Czech Republic
facility: GSK Investigational Site
city: Praha 6
country: Czech Republic
facility: GSK Investigational Site
city: Praha 9
country: Czech Republic
facility: GSK Investigational Site
city: Znojmo
country: Czech Republic
facility: GSK Investigational Site
city: Espoo
country: Finland
facility: GSK Investigational Site
city: Helsinki
country: Finland
facility: GSK Investigational Site
city: Hyvinkaa
country: Finland
facility: GSK Investigational Site
city: Jarvenpaa
country: Finland
facility: GSK Investigational Site
city: Jyvaskyla
country: Finland
facility: GSK Investigational Site
city: Kokkola
country: Finland
facility: GSK Investigational Site
city: Kotka
country: Finland
facility: GSK Investigational Site
city: Kuopio
country: Finland
facility: GSK Investigational Site
city: Lahti
country: Finland
facility: GSK Investigational Site
city: Oulu
country: Finland
facility: GSK Investigational Site
city: Pori
country: Finland
facility: GSK Investigational Site
city: Riihimaki
country: Finland
facility: GSK Investigational Site
city: Seinajoki
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Tampere
country: Finland
facility: GSK Investigational Site
city: Turku
country: Finland
facility: GSK Investigational Site
city: Vantaa
country: Finland
facility: GSK Investigational Site
city: Vantaa
country: Finland
facility: GSK Investigational Site
city: Boulogne
country: France
facility: GSK Investigational Site
city: Chalons en Champagne
country: France
facility: GSK Investigational Site
city: Chambéry
country: France
facility: GSK Investigational Site
city: Courbevoie
country: France
facility: GSK Investigational Site
city: Draguignan
country: France
facility: GSK Investigational Site
city: Essey les Nancy
country: France
facility: GSK Investigational Site
city: Floirac
country: France
facility: GSK Investigational Site
city: Gradignan
country: France
facility: GSK Investigational Site
city: Issy les Moulineaux
country: France
facility: GSK Investigational Site
city: Le Havre
country: France
facility: GSK Investigational Site
city: Les Lilas
country: France
facility: GSK Investigational Site
city: Manosque
country: France
facility: GSK Investigational Site
city: Maromme
country: France
facility: GSK Investigational Site
city: Maurepas
country: France
facility: GSK Investigational Site
city: Nogent Sur Marne
country: France
facility: GSK Investigational Site
city: Nogent-sur-Marne
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Rosny Sous Bois
country: France
facility: GSK Investigational Site
city: Rouen
country: France
facility: GSK Investigational Site
city: Saint Quentin
country: France
facility: GSK Investigational Site
city: Thionville
country: France
facility: GSK Investigational Site
city: Birkenfeld
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Mannheim
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Oberkirch
country: Germany
facility: GSK Investigational Site
state: Baden-Wuerttemberg
city: Freising
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Kaufering
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Muenchen
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Eschwege
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Fulda
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Wiesbaden
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Buetzow
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Rostock
country: Germany
facility: GSK Investigational Site
state: Mecklenburg-Vorpommern
city: Salzgitter
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Wolfenbuettel
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Bochum
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Detmold
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Espelkamp
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Goch
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Guetersloh
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Loehne
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Minden
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Oberhausen
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Velbert
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Willich
country: Germany
facility: GSK Investigational Site
state: Nordrhein-Westfalen
city: Trier
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Cossebaude
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Leipzig
country: Germany
facility: GSK Investigational Site
state: Sachsen
city: Flensburg
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Gluecksburg
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Roma
country: Italy
facility: GSK Investigational Site
state: Lazio
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Bari
country: Italy
facility: GSK Investigational Site
state: Puglia
city: Ragusa
country: Italy
facility: GSK Investigational Site
state: Sicilia
city: Almería
country: Spain
facility: GSK Investigational Site
city: Baracaldo (Vizcaya)
country: Spain
facility: GSK Investigational Site
city: Baracaldo
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Berango (Vizcaya)
country: Spain
facility: GSK Investigational Site
city: Bilbao
country: Spain
facility: GSK Investigational Site
city: Blanes
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Munguía (Vizcaya)
country: Spain
facility: GSK Investigational Site
city: Móstoles/Madrid
country: Spain
facility: GSK Investigational Site
city: San Vicent dels Horts
country: Spain
facility: GSK Investigational Site
city: Sant Adriá de Beyós, Barcelona
country: Spain
facility: GSK Investigational Site
city: Sant Eugenia de Berga, Barcelona
country: Spain
facility: GSK Investigational Site
city: Sodupe (Vizcaya)
country: Spain
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: Soriano-Gabarró M et al. (2008) Potential impact of Rotarix according to rotavirus type distribution. Pediatr Infect Dis J. 27(1) Supplement: S28-S32.
citation: Vesikari T, Karvonen A, Prymula R, Schuster V, Tejedor JC, Cohen R, Meurice F, Han HH, Damaso S, Bouckenooghe A. Efficacy of human rotavirus vaccine against rotavirus gastroenteritis during the first 2 years of life in European infants: randomised, double-blind controlled study. Lancet. 2007 Nov 24;370(9601):1757-63. doi: 10.1016/S0140-6736(07)61744-9.
citation: Vesikari T, Prymula R, Schuster V, Tejedor JC, Cohen R, Bouckenooghe A, Damaso S, Han HH. Efficacy and immunogenicity of live-attenuated human rotavirus vaccine in breast-fed and formula-fed European infants. Pediatr Infect Dis J. 2012 May;31(5):509-13. doi: 10.1097/INF.0b013e3182489cac.