| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Healthy volunteers (Active immunisation of infants against gastroenteritis (GE) due to rotavirus (RV)) |
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| E.1.1.1 | Medical condition in easily understood language |
| Rotavirus gastroenteritis |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Virus Diseases [C02] |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
To assess the efficacy of two doses of GSK Biologicals’ liquid HRV vaccine against severe RV GE caused by the circulating wild-type RV strains during the efficacy follow-up period.
Criteria: The primary objective will be reached if the lower limit of the 95% Confidence Interval (CI) on vaccine efficacy is at least 10%.
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| E.2.2 | Secondary objectives of the trial |
•To assess the efficacy of 2 doses of HRV vaccine during the efficacy follow-up period against
-any RV GE caused by circulating wild-type RV strain & hospitalisation due to it, any & severe RV GE caused by G1 & by non-G1 type RV strains
-any & severe all cause GE
At Visit 3 & 6, to assess:
•in immunogenicity sub-cohort (SC) 1, the serum anti-rotavirus Ab SCR of HRV group compared to the placebo group & seropositivity rate & when co-ad with the routine childhood vaccines in immunogenicity SC2
•in SC1 immunogenicity of HRV vaccine in terms of serum anti-rotavirus Ab conc & when co-ad with the routine childhood vaccines in SC2.
•Immunogenicity SC2: effect of HRV vaccine on the immune response to all Ags contained in each of the co-ad childhood vaccines
•In terms of occurrence of solicited AEs, reactogenicity of the co-ad vaccines when co-ad with HRV vaccine/placebo in immunogenicity SC2 & of the HRV vaccine/placebo in the rest
•HRV vaccine safety in terms of unsolicited AEs & SAEs |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
•Subjects who the investigator believes that their parents/Legally Acceptable Representatives (LARs) can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
•A male or female infant of Chinese origin between, and including, 6 and 16 weeks (42-112 days) of age at the time of the first vaccination.
•Written informed consent obtained from the parents/LARs of the subject.
•Healthy subjects as established by medical history and clinical examination before entering into the study.
•Born after a gestation period of 36 to 42 weeks inclusive.
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| E.4 | Principal exclusion criteria |
•Child in care.
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
•Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs since birth. For corticosteroids, prednisone 0.5 mg/kg/day, or equivalent, inhaled and topical steroids are allowed.
•Planned administration/administration of a vaccine not foreseen by the study protocol within 14 days before each dose of study vaccines and ending 14 days after f the first dose of the HRV vaccine or placebo except for the routine childhood vaccinations.
•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).
•Any clinically significant history of gastrointestinal disease including any uncorrected congenital malformation (such as Meckel’s diverticulum) of the gastrointestinal tract that would predispose for Intussusception (IS).
•Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
•Family history of congenital or hereditary immunodeficiency.
•History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
•Major congenital defects or serious chronic illness.
•History of confirmed RV GE.
•Acute disease and/or fever at the time of enrolment.
-Fever is defined as temperature (37.1°C on axillary setting as defined by the Chinese authorities.
-Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator (warrants deferral of the vaccination).
•GE within 7 days preceding the study vaccine or placebo administration (warrants deferral of the vaccination).
•Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period.
In addition to the criteria mentioned above, the following criteria will be applicable to all subjects in the immunogenicity sub-cohort 2:
•History of diphtheria, tetanus and pertussis disease.
•History of seizures or progressive neurological disease.
•Previous vaccination against diphtheria, tetanus, pertussis and poliomyelitis.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Occurrence of severe RV GE caused by the circulating wild-type RV strains in subjects vaccinated with liquid HRV vaccine/placebo. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| During the efficacy follow-up period (two weeks post-Dose 2 till Visit 7) |
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| E.5.2 | Secondary end point(s) |
Occurrence of any and severe RV GE caused by the circulating wild-type RV strains, G1 and non-G1 type strains, and hos-pitalisation due to RV GE by circulating wild-type RV strains during the efficacy follow-up period in subjects vaccinated with liquid HRV vaccine/placebo.
Anti-rotavirus IgA antibody concentrations in terms of serocon-version rate at Visit 3 and (SCR), seropositivity rate at Visit 6.,
Serum anti-rotavirus IgA antibody concentrations expressed as and geometric mean concentration (GMC)
Anti-tetanus, anti-diphtheria, anti-pertussis toxoid (PT), anti-filamentous haemagglutinin (FHA), anti-pertactin (PRN), anti-poliovirus type 1, anti-poliovirus type 2 and anti-poliovirus type 3 antibody concentrations/titres and seroprotection/seropositivity rates at Visit 5.
Occurrence of each general solicited symptom (fever, fussi-ness/irritability, loss of appetite, cough/runny nose, diarrhoea and vomiting)
Occurrence of local (pain, swelling, redness) and general solic-ited symptoms (fever, irritability/fussiness, drowsiness, loss of appetite and gastrointestinal symptoms)
Occurrence of unsolicited symptoms after any dose of liquid HRV vaccine or placebo, according to the Medical Dictionary for Regulatory Activities (MedDRA) classification.
Occurrence of SAEs, according to the MedDRA classification. |
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Occurrence of RV GE: During the efficacy follow-up period (two weeks post-Dose 2 till Visit 7
Antirotavirus seroconversion and seropositivity: At Visit 3 (SCR) and at Visit 6 (Seropositivity rate) At Visits 3 and 6 (GMC)
Other seroprotection and seropositivity: At Visit 5
General and local symptoms: Within the 8-day (Days 0 to Day -7) follow-up period after each dose of liquid HRV vaccine dose/ placebo.
Unsolicited symptoms: Day 0 to Day 30 after each vaccine dose
SAEs: Throughout study period |
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| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | Yes |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | No |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
Will this trial be conducted at a single site globally?
| No |
| E.8.4 | Will this trial be conducted at multiple sites globally? | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Yes |
| E.8.6.3 | Specify the countries outside of the EEA in which trial sites are planned |
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| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
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