A phase III study to assess the efficacy, immunogenicity and safety of GSK Biologicals’ human rotavirus (HRV) vaccine given concomitantly with routine expanded program on immunisation (EPI) vaccinations including oral poliovirus vaccine (OPV) in healthy infants across 6 countries in Latin America.

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2015-001540-10-Outside-EU/EEA
• Date of registration: 11/06/2015
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: A phase III study to assess the efficacy, immunogenicity and safety of GSK Biologicals’ human rotavirus (HRV) vaccine given concomitantly with routine expanded program on immunisation (EPI) vaccinations including oral poliovirus vaccine (OPV) in healthy infants across 6 countries in Latin America.
• Scientific title: A phase III, double-blind, randomised, placebo-controlled, multi-country and multi-center study to assess the efficacy, immunogenicity and safety of two doses of GSK Biologicals’ oral live attenuated human rotavirus (HRV) vaccine given concomitantly with routine expanded program on immunisation (EPI) vaccinations including oral poliovirus vaccine (OPV) in healthy infants. - Rota-024
• Target sample size: 6568
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001540-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Argentina, Brazil, Colombia, Dominican Republic, Honduras, Panama

Contacts

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

• Name: Clinical Disclosure Advisor
• Affiliation: GlaxoSmithKline Biologicals

Key inclusion & exclusion criteria

Inclusion criteria:
-Subjects who the investigator believed that their parents/guardians could and would comply with the requirements of the protocol
-A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination according to the country recommendations for the routine vaccination schedules.
-Written informed consent obtained from the parent or guardian of the subject, prior any study procedure.
-Free of obvious health problems as established by medical history and clinical examination before entering into the study.

Are the trial subjects under 18? yes
Number of subjects for this age range: 6568
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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.
-Child was 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 pe-riod.
-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.



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Rotavirus gastroenteritis

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Trade Name: Rotarix
Pharmaceutical Form: Powder and solvent for oral suspension
INN or Proposed INN: -
Other descriptive name: HUMAN ROTAVIRUS RIX4414 STRAIN (LIVE ATTENUATED)
Concentration unit: log10 CCID50/dose log10 cell culture infective dose 50/dose
Concentration type: equal
Concentration number: 6.5-
Pharmaceutical form of the placebo: Powder and solvent for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: 2 weeks after Dose 2 until the infant turns one year of age

Primary end point(s): Occurrence of severe RV GE caused by the wild RV strains

Secondary Objective: To assess if severe RVGE can be prevented by HRV vaccine, caused by wild RV strain serotype G1, non-G1 serotypes and due to each non-G1 during the period starting from 2 weeks after Dose 2 until 1 year of age.
To assess severe RVGE can be prevented by HRV vaccine after 1st dose.
To assess safety (SAEs) throughout the study period.
In a subset of 300 subjects, to explore the effect of HRV vaccine on immune response to concurrently administered routine EPI vaccinations and to assess immunogenicity of anti-RV IgA antibody concentrations 1 to 2 months after the 2nd dose.
In a subset of 900 subjects, to demonstrate NI of HRV over placebo group in terms of immune response to concurrently administered OPV, 1 month after Dose 3 in a subset with no OPV given in neonatal period and to explore the effect of HRV vaccine on immune response, 1 month after Dose 1 and 2 of OPV in a subset with no OPV given in neonatal period and after Dose 1, 2 and 3 in a subset with OPV given in neonatal period.

Main Objective: To determine if two doses of GSK Biologicals’ HRV vaccine given concomitantly with routine EPI vaccinations including OPV can prevent severe RV GE caused by the circulating wild-type RV strains during the period starting from 2 weeks after Dose 2 until one year of age.

Secondary Outcome(s)

Secondary end point(s): Occurrence of severe RV GE caused by the wild RV strain of serotype G1.
Occurrence of severe RV GE due to non-G1 serotypes
Occurrence of severe RV GE due to each non-G1 serotype
Occurrence of severe RV GE caused by the circulating wild RV strains, of severe RV GE caused by the wild RV strain of serotype G1, of severe RV GE due to non-G1 serotypes and of severe RV GE due to each non-G1 serotype
Safety endpoint
Occurrence of SAEs
Immunogenicity endpoints
In a subset of 300 subjects:
Serum rotavirus IgA antibody concentrations
GMTs for anti-polio type 1, 2 and 3 antibodies.
Seroprotection status:
anti-poliovirus serotype 1, 2 and 3 antibody titre greater than or equal to 8
One to two months after the third dose of routine EPI vaccinations (at Visit 4):
Geometric mean antibody concentrations (GMC)/geometric mean antibody titres (GMT) for anti-PRP, anti-diphtheria and anti-tetanus, anti-BPT, anti- poliovirus serotypes 1, 2 and 3, and anti-HBsAg antibodies.
Seroprotection status:
anti-PRP antibody concentration greater than or equal to 0.15 and 1.0 mcg/ml
anti-diphtheria toxoid antibody concentration greater than or equal to 0.1 IU/ml
anti-tetanus toxoid antibody concentration greater than or equal to 0.1 IU/ml
anti-HBsAg antibody concentration greater than or equal to 10.0 mIU/ml
anti-poliovirus serotype 1, 2 and 3 antibody titre greater than or equal to 8
Seropositivity status:
anti-BPT antibody concentrations greater than or equal to 15 EL.U/ml
In a subset of 900 subjects:
GMTs for anti-polio type 1, 2 and 3 antibodies
Seroprotection status:
anti-poliovirus serotype 1, 2 and 3 antibody titre greater than or equal to 8

Timepoint(s) of evaluation of this end point: RV GE caused by wild RV strain of serotype G1, non-G1 and each non-G1 and circulating wild RV strains, serotype G1, non-G1 and each non-G1 serotype: 2 weeks after Dose 2 until the infant turns 1 year of age and from Day 0 until the infant turns 1 year of age respectively.
SAEs:Day 0-infant turns 1 year of age
Subset of 300:RV IgA antibody, GMTs and seroprotection for anti-poliotypes 1,2 and 3:1 to 2 months after the 2nd dose (Visit 3). GMC/T and seroprotection status for anti-PRP, D, T, poliovirus types 1, 2 and 3, and HBsAg. GMC/T and seropositivity status for anti-BPT: 1 to 2 months after the 3rd dose of routine EPI vaccinations (Visit 4)
Subset of 900: GMT and seroprotection status for anti-polio type 1, 2 and 3:1 month after each dose of routine EPI vaccinations (Visits 2, 4 and 6)

Secondary ID(s)

444563/024

Source(s) of Monetary Support

GlaxoSmithKline Biologicals