Study to evaluate the efficacy, safety and immunogenicity of two or three doses of GSK Biologicals’ oral live attenuated human rotavirus (HRV) vaccine given concomitantly with routine EPI vaccinations in healthy infants.

• Register: EUCTR
• Last refreshed on: 10 July 2015
• Main ID: EUCTR2015-001485-26-Outside-EU/EEA
• Date of registration: 22/06/2015
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline Biologicals
• Public title: Study to evaluate the efficacy, safety and immunogenicity of two or three doses of GSK Biologicals’ oral live attenuated human rotavirus (HRV) vaccine given concomitantly with routine EPI vaccinations in healthy infants.
• Scientific title: A phase III, double-blind, randomised, placebo-controlled, multi-center study to assess the efficacy, safety and immunogenicity of two or three doses of GSK Biologicals’ oral live attenuated human rotavirus (HRV) vaccine given concomitantly with routine EPI vaccinations in healthy infants. - Rota-037, Rota-037 EXT:Y2
• Target sample size: 4941
• Recruitment status: NA
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2015-001485-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no 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

Malawi, South Africa

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 believes that their parents/guardians can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits) 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 (i.e. parent/guardian should be 18 years or older). (South Africa-specific Amendment 5: 10 July 2006)
•Healthy subjects as established by medical history and clinical examination before entering into the study.
•In South Africa, birth weight > 2000 g or if weight un-known, gestation period > 36 weeks.
Are the trial subjects under 18? yes
Number of subjects for this age range: 4941
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 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 (pharmaceutical product or device).
•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 al-lowed.)
•History of use of experimental rotavirus vaccine.
•Previous routine vaccination except BCG, HBV and OPV vaccination at birth (should be documented in the CRF). (Amendment 1: 24 August 2005)
•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 (no laboratory testing required).
•History of allergic disease or reaction likely to be exacer-bated 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).) (warrants deferral of vaccination).
•Gastroenteritis within 7 days preceding the first study vaccine administration (warrants deferral of the vaccina-tion).
•Previous cofirmed occurrence of RV GE.
•A family history of congenital or hereditary immunodefi-ciency.
•Administration of immunoglobulins and/or blood products since birth or planned administration during the study pe-riod.
•History of any neurologic disorders or seizures.
•Acute or chronic, clinically significant pulmonary, cardio-vascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests.


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

Health Condition(s) or Problem(s) studied

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

Healthy volunteers

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: not less then
Concentration number: 6.0-
Pharmaceutical form of the placebo: Powder and solvent for oral suspension
Route of administration of the placebo: Oral use

Primary Outcome(s)

Secondary Objective: •To assess efficacy of HRV vaccine given concomitantly with routine EPI vaccinations in terms of
-hospitalisation and/or supervised re-hydration therapy in a medical facility for RV GE caused by circulating wild-type RV strains
-severe RV GE caused by circulating wild-type RV strains after 3 doses vs 2 doses
-severe RV GE (>11 on the 20-point Vesikari scoring system) caused by circulating wild-type RV strains, wild type G1, non-G1 & severe RVGE in for the South African subset of subjects who were fully vaccinated before start of the RV season
-Any RV GE caused by circulating wild-type RV strains
•To assess safety of 2 or 3 doses of HRV vaccine compared with placebo in terms of AEs leading to drop-out and SAEs
•To assess immunogenicity of HRV vaccine in terms of anti-rotavirus IgA antibody seroconversion, seropositivity rate & serum antibody concentrations

Main Objective: To determine if the GSK Biologicals' HRV vaccine (pooled HRV groups) given concomitantly with routine EPI vaccinations can prevent severe RV GE (>11 on the 20-point Vesikari scoring system) 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 6.
Criteria: The primary objective will be reached if the lower limit of the 95% CI on vaccine efficacy is >0%.

Primary end point(s): Occurrence of severe RV GE (score > 11 on a 20-point Vesikari scoring system caused by the circulating wild-type RV strains in pooled HRV groups versus the placebo group.

Timepoint(s) of evaluation of this end point: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 6.

Secondary Outcome(s)

Secondary end point(s): Occurrence of hospitalisation and/or supervised re-hydration therapy (equivalent to WHO plan B or C) in a medical facility for RV GE caused by the circulating wild-type RV strains.
Occurrence of severe RV GE caused by the circulating wild-type RV strains of G1 serotype.
Occurrence of severe RV GE caused by the circulating wild-type RV strains of non-G1 serotype.
Occurrence of any and severe RV GE caused by the circulating wild-type RV strains.
Occurrence of severe GE.
Occurrence of severe RV GE caused by the circulating wild-type RV strains.
In South Africa, occurrence of severe RV GE caused by the circulating wild-type RV strains for the subset of subjects who were fully vaccinated before the beginning of the RV season

For subjects in Cohort 2 South Africa and the cohort in Malawi:
Occurrence of severe RV GE (score >= 11 on a 20-point Vesikari scoring system caused by the circulating wild-type RV strains
Occurrence of hospitalisation and/or supervised re-hydration therapy (equivalent to WHO plan B or C) in a medical facility for RV GE caused by the circulating wild-type RV strains
Occurrence of severe RV GE caused by the circulating wild-type RV strains of G1 serotype.
Occurrence of severe RV GE caused by the circulating wild-type RV strains of non-G1 serotype
For all subjects, occurrence of AEs/SAEs leading to drop-out
In a subset of subjects, seroconversion rate and Geometric Mean concentration (GMC) to anti-rotavirus IgA antibody
In all subjects, seropositivity rate and GMC to anti-rotavirus IgA antibody

Timepoint(s) of evaluation of this end point: RV GE and Hospitalisation: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 6.
Severe RV GE: During the period starting from Dose 1 of the study vaccine until Visit 6.
South Africa: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 6
Cohort 2: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 7, and from Visit 6 to Visit 7
G1 serotype: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 7, and from Visit 6 to Visit 7
Non-G1 serotype: During the period from 2 weeks after the last dose of HRV vaccine or placebo until Visit 7, and from Visit 6 to Visit 7
AEs/SAEs: Throughout the entire study period
Immunogenicity: At Visit 4

Secondary ID(s)

102248,111274

Source(s) of Monetary Support

GlaxoSmithKline Biologicals