To Assess Safety, Reactogenicity & Immunogenicity of 2 Doses of GSK's Oral Human Rotavirus Vaccine in Pre-Term Infants

Study Overview
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Brief Summary
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This study is planned to evaluate the safety (in terms of occurrence of any serious adverse events), reactogenicity (any side effects) and immunogenicity (ability of the vaccine to develop antibodies that fight infection) of the HRV vaccine when used in pre-term infants aged between 6 and 14 weeks at the time of the first dose in Portugal, France and Poland and in pre-term infants aged between 6 and 12 weeks at the time of first dose in Spain. The study will be performed in four European countries (France, Poland, Spain, and Portugal). The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Detailed Description
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This is a Phase 3b study. Each study group is further stratified into two sub-groups depending on the gestational age at birth of the subject: Stratum I: very pre-term infants, born after a gestational period of 27-30 weeks (189-216 days) (20% of enrolment). Stratum II: mild pre-term infants born after a gestational period of 31-36 weeks (217-258 days) (80% of enrolment). The study will be conducted in a double-blind manner with respect to the HRV vaccine and placebo. The study will not be blinded with respect to the type of concomitantly administered routine infant vaccination. In accordance with the local National Plan of Immunisation schedule in each of the respective participating countries, GSK Biologicals' Infanrix Hexa™ (DTPa-HBV-IPV/Hib), Infanrix Quinta™ (DTPa-IPV-Hib), Infanrix™+IPV+Hib (DTPa+IPV+Hib) and/or Engerix-B™ (HBV) will be co-administered (at a maximum interval of two days from each other) with each HRV vaccine or placebo dose. Hepatitis B and Bacille Calmette-Guérin vaccines (BCG) at birth are allowed if included in the local National Plan of Immunisation schedule in participating countries. At the discretion of the investigator the following vaccines may be administered during each subject's study participation: Vaccine against Streptococcus pneumoniae (Prevenar®) in France and Spain (concomitantly with HRV vaccine/Placebo). Vaccine against Neisseria meningitidis (Neis Vacc C®) is allowed if there is at least 14-days interval with respect to the administration of the HRV vaccine/Placebo.

Official Title
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Phase IIIb, Double Blind, Randomised, Placebo-Controlled, Multi-Country/Centre, Study to Assess Safety, Reactogenicity & Immunogenicity of 2 Doses of GSK Biologicals' Oral Live Attenuated Human Rotavirus (HRV) Vaccine in Pre-Term Infants

Conditions
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Infections, Rotavirus

Intervention / Treatment
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* Biological: Rotarix™
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol should be enrolled in the study. Healthy male or female infant between, and including, 6 and 14 weeks (42 - 104 days) of age at the time of first study vaccination in Portugal, France and Poland. A male or female infant between, and including, 6 and 12 weeks of age at the time of first study vaccination in Spain. Medically stable pre-term infants, born within a gestational period of 27 -36 weeks. Written informed consent obtained from the parent or guardian of the subject. Planned to be discharged from hospital's neonatal stay on or before the day of the first HRV vaccine/Placebo administration. Exclusion Criteria: Use of any investigational or non-registered product (drug or vaccine) other than the HRV vaccine within 30 days preceding the first dose of HRV vaccine, or planned use during the study period. Chronic administration of immunosuppressants or other immune-modifying drugs since birth. Planned administration/ administration of a vaccines not foreseen by the study protocol from birth till study end. 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 chronic gastrointestinal disease. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Major congenital defects or serious chronic illness (subjects with severe broncho-pulmonary dysplasia requiring persistent oxygen-therapy will be excluded). History of any neurologic disorders or seizures. Grade I and II intra-ventricular bleeding are allowed. Acute disease at the time of enrolment. Administration of immunoglobulins, and/or any blood products within one month (30 days) preceding the first dose of study vaccines or planned administration during the study period. Monoclonal anti-RSV therapy/prophylaxis and recombinant erythropoietin are allowed.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 14 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: Rotarix Group<br>All subjects received 2 oral doses of Rotarix vaccine, 1 dose at Day 0 and 1 dose at Month 1 or 2 depending on the country. | Biological: Rotarix™<br>* Two-dose oral vaccination.<br>|
| Placebo Comparator: Placebo Group<br>All subjects received 2 oral doses of placebo, 1 dose at Day 0 and 1 dose at Month 1 or 2 depending on the country. | Biological: Placebo<br>* Two-dose oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Any Serious Adverse Events (SAEs). | An SAE is any untoward medical occurrence that: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study subject, or may evolve into one of the outcomes listed above. | From Day 0 up to 1 month after Dose 2 of Rotarix vaccine/Placebo | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Reporting Unsolicited Adverse Events (AEs), According to Medical Dictionary for Regulatory Activities (MedDRA) Classification. | An AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. | Within 31 days after any Rotarix vaccine/Placebo dose. | 
| Number of Subjects for Whom Each Type of Solicited Symptom Was Reported. | Solicited symptoms included Diarrhea (3 or more looser than normal stools/day), Fever (axillary temperature ≥ 37.5 degrees Celsius (°C)), Irritability, Loss of appetite, and Vomiting | Within 15 days after each Rotarix vaccine/Placebo dose. | 
| Number of Subjects for Whom Presence of Rotavirus (RV) Gastroenteritis (GE) Was Detected in Stools. | Gastroenteritis (GE): diarrhoea with or without vomiting. Rotavirus (RV) GE: A GE episode was a RV GE if a stool sample taken during or not later than 7 days after the episode was RV positive by Enzyme Linked Immunosorbent Assay. | From Dose 1 up to 1 month after Dose 2 of Rotarix vaccine/Placebo | 
| Seroconversion to Anti-rotavirus Immunoglobulin A (IgA) Antibody. | Number of subjects with anti-rotavirus IgA antibody concentration ≥ 20 Units/milliliter (U/mL). | At Visit 3, 1 month after Dose 2 of Rotarix vaccine/Placebo | 
| Serum Anti-Rotavirus IgA Antibody Concentration. | Anti-rotavirus IgA antibody concentrations are given as geometric mean concentrations (GMC) with 95% Confidence Intervals, calculated on all subjects. | At Visit 3, 1 month after Dose 2 of Rotarix vaccine/Placebo |