Safety Study of 2 Formulations of GSK's Human Rotavirus (HRV) Vaccine (444563), in Healthy Infants Starting at Age 6-12 Weeks

Study Overview
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Brief Summary
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The purpose of this study is to complete the total safety database size for GlaxoSmithKline Biologicals' (GSK's) human rotavirus (HRV) vaccine across the Porcine circovirus (PCV)-free development plan. This study used a purposely selected lot for PCV-free liquid HRV vaccine that is in the upper range of the usual release potencies. The PCV-free liquid HRV vaccine lots used were stored frozen in order to keep the titer stable until administration during the study. As the liquid formulation of GSK's HRV vaccine is not licensed in the US, the lyophilized formulation of the vaccine was used as a control in all phase III studies as part of the PCV-free development plan.

Official Title
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A Phase III, Observer-blind, Randomized, Multi-country Study to Assess the Reactogenicity and Safety of the Porcine Circovirus (PCV) Free Liquid Formulation of GSK's Oral Live Attenuated Human Rotavirus (HRV) Vaccine as Compared to the Lyophilized Formulation of the GSK's HRV Vaccine, When Administered as a 2-dose Vaccination in Infants Starting at Age 6-12 Weeks

Conditions
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Infections, Rotavirus

Intervention / Treatment
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* Biological: PCV-free liquid formulation of GSK's oral live attenuated HRV vaccine
* Biological: Lyophilized formulation of GSK's oral live attenuated HRV vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects must satisfy all the following criteria at study entry: Subjects' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply, with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits). Written or witnessed/thumb printed informed consent obtained from the parent(s)/LAR(s) of the subject prior to performance of any study specific procedure. Healthy subjects as established by medical history and clinical examination before entering into the study. A male or female between, and including, 6 and 12 weeks (42-90 days) of age at the time of the first vaccination. Exclusion Criteria: Medical conditions Uncorrected congenital malformation (such as Meckel's diverticulum) of the gastrointestinal tract that would predispose for Intussusception (IS). Very prematurely born infants (born ≤28 weeks of gestation). History of IS. Family history of congenital or hereditary immunodeficiency. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Hypersensitivity to latex. Major congenital defects or serious chronic illness, as assessed by the investigator. Previous confirmed occurrence of Rotavirus Gastroenteritis (RV GE). History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines. History of Severe combined immunodeficiency (SCID). Prior/Concomitant therapy Use of any investigational or non-registered product (drug, vaccine or medical device) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 1), or planned use during the study period. Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting 30 days before the first dose and ending 30 days after the last dose of study vaccine administration, with the exception of the inactivated influenza vaccine, which is allowed at any time during the study, and other licensed routine childhood vaccinations. Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab). Administration of immunoglobulins and/or any blood products from birth or planned administration 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, this will mean prednisone ≥0.5 mg/kg/day, or equivalent. Inhaled and topical steroids are allowed. Previous vaccination against RV. Prior/Concurrent clinical study experience 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 vaccine/product (drug or medical device). Other exclusions • Child in care.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 12 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HRV PCV-free Liq Group<br>Subjects aged 6 to 12 weeks at the time of first vaccination, who received two doses of oral live-attenuated human rotavirus (HRV) porcine circovirus (PCV)-free vaccine in liquid formulation, one at Day 1 and one at Month 1 or Month 2, according to the immunization schedule for rotavirus (RV) vaccine administration in participating countries. PCV-free implies no detection of PCV-1 and PCV-2 according to the limit of detection of the tests used. | Biological: PCV-free liquid formulation of GSK's oral live attenuated HRV vaccine<br>* 2 doses administered orally at Day 1 and at Month 1 or Month 2, according to the immunization schedule for RV vaccine administration in participating countries.<br>|
| Active Comparator: HRV Lyo group<br>Subjects aged 6 to 12 weeks at the time of first vaccination, who received two doses of oral live-attenuated human rotavirus (HRV) vaccine in lyophilized formulation, one at Day 1 and one at Month 1 or Month 2, according to the immunization schedule for rotavirus (RV) vaccine administration in participating countries. | Biological: Lyophilized formulation of GSK's oral live attenuated HRV vaccine<br>* 2 doses administered orally at Day 1 and at Month 1 or Month 2, according to the immunization schedule for RV vaccine administration in participating countries.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Any Solicited General Adverse Events (AEs) After the First Vaccination | Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (defined as passage of three or more looser than normal stools within a day), vomiting (defined as one or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day), loss of appetite and cough/runny nose. Any = occurrence of AE regardless of intensity grade or relation to study vaccination. | During the 8-day follow-up period after the first vaccination (vaccines administered at Day 1) | 
| Number of Subjects With Any Solicited General Adverse Events (AEs) After the Second Vaccination | Assessed solicited general AEs were fever (defined as temperature ≥ 38.0°C/100.4°F, the preferred location for measuring temperature in this study being the oral cavity, the axilla and the rectum), irritability/fussiness, diarrhea (defined as passage of three or more looser than normal stools within a day), vomiting (defined as one or more episodes of forceful emptying of partially digested stomach contents ≥1 hour after feeding within a day), loss of appetite and cough/runny nose. Any = occurrence of AE regardless of intensity grade or relation to study vaccination. | During the 8-day follow-up period after the second vaccination (vaccines administered at Month 1 or Month 2) | 
| Number of Subjects With Any Unsolicited AEs | An unsolicited AE is defined as any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment, and reported in addition to those solicited during the clinical study and any 'solicited' AE with onset outside the specified period of follow-up for solicited symptoms. Any = occurrence of AE regardless of intensity grade or relation to study vaccination. | During the 31-day follow-up period across doses (vaccines administered at Day 1 and at Month 1 or Month 2) | 
| Number of Subjects With Any Serious Adverse Events (SAEs) | An SAE is defined as any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization and/or results in disability/incapacity. Any = occurrence of SAE regardless of intensity grade or relation to study vaccination. | Throughout the study period (from Day 1 up to Month 7 or Month 8) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HRV, Lyophilized formulation, Liquid formulation, Human rotavirus vaccine, Rotarix, Healthy infants, PCV-free, Porcine circovirus-free