A Study to Explore the Existence of Horizontal Transmission of the RIX4414 Vaccine Strain Between Twins Within a Family.

Study Overview
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Brief Summary
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The aim of this study is to explore horizontal transmission of the HRV (Human Rotavirus) vaccine strain within a family from the twin vaccinated with Rotarix to the twin receiving placebo. 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. Three doses of Infanrix® hexa will be administered to all subjects at the discretion of the investigator. One complimentary dose of Rotarix will be administered to all infants enrolled in this study (both study groups) who are aged less than 6 months at Visit 3 (Week 13) as a benefit to the placebo group for participation in the study. The study will be conducted in a double-blind manner with respect to Rotarix and placebo administered at Visit 1 and Visit 2. The parents/guardians of the subjects will know that within each pair of twins, one subject will receive the Rotarix vaccine and one subject will receive the placebo. The study will be open label with respect to administration of the Rotarix vaccine dose given at Visit 3 to all subjects in each group who are aged less than 6 months.

Official Title
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A Phase IIIb, Randomized, Double-Blind, Placebo-Controlled Study to Explore the Existence of Horizontal Transmission of the RIX4414 Vaccine Strain Between Twins Within a Family.

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 with a live twin living in the same household who is also enrolled in this study. Born after a gestation period of ≥32 weeks, Discharged from hospital neonatal care stay, 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. A male or female between, and including, 6 and 14 weeks of age at the time of the first study vaccination. Healthy subjects as established by medical history and clinical examination before entering into the study. Written informed consent obtained from the parent or guardian of the subjects. 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. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required). Any clinically significant history of chronic gastrointestinal disease. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Acute disease at time of enrolment. Administration of immunoglobulins and/or any blood products since birth or planned administration during the study period. Contact with an immunosuppressed individual. 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). Chronic administration of immunosuppressants since birth. Gastroenteritis within 7 days preceding the first study vaccine administration. Documented HIV-positive subject.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotarix Group<br>All subjects received 2 oral doses of Rotarix vaccine at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | Biological: Rotarix<br>* Two-dose oral vaccination.<br>|
| Placebo Comparator: Placebo Group<br>All subjects received 2 oral doses of placebo at Day 0 (Visit 1) and Week 7 (Visit 2). Subjects aged less than 6 months at Visit 3 received one complimentary Rotarix vaccine dose at Week 13 (Visit 3). | Biological: Rotarix<br>* Two-dose oral vaccination.<br>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 |
| --- | --- | --- |
| Presence of Rotavirus Vaccine Strain in Any Stool Sample From Twin Receiving Placebo. | Number of subjects in the Placebo Group with rotavirus vaccine strain in at least one stool sample. | On the day of each vaccine/placebo dose, then three times weekly for 6 consecutive weeks starting after each vaccine/placebo dose and on the day of Visit 3. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Human Rotavirus (HRV) Shedding Per Study Group. | Duration of shedding in the Placebo Group= number of days between first and last stool sample positive (+) for rotavirus (RV) antigen and in the Rotarix Group= number of days between the day of vaccination and the date of last stool sample + for RV antigen. | From Day 0 up to Week 13. | 
| Number of Genetic Variation Differences Detected by Sequencing of Genomic Mutations in the HRV Vaccine Strain After Transmission. | Dissimilar amino acid substitutions in the HRV vaccine strain isolated from the twin receiving placebo, when compared to the genetic variation of HRV vaccine strain isolated from the Rotarix vaccine recipients, were counted as genetic variation differences. | During the entire study period (up to Visit 4, Week 17). | 
| Live Viral Vaccine Load in the Stool of the Twin Receiving Placebo in Case of Transmission. | Number of subjects in the Placebo Group with live virus identified in at least one stool sample in case of transmission. | During the entire study period (up to Visit 4, Week 17). | 
| Anti-rotavirus Immunoglobulin A (IgA) Antibody Seroconversion. | Number of initially seronegative subjects with anti-rotavirus IgA antibody concentration ≥ 20 Units/milliliter (U/mL), 1 month after the second dose. | At Visit 3 (Week 13). | 
| Anti-rotavirus IgA Antibody Concentration. | Anti-rotavirus IgA antibody concentrations are given as geometric mean concentrations (GMC) with 95% Confidence Intervals. | At Visit 3 (Week 13). | 
| Number of Subjects With Gastroenteritis (GE) and Rotavirus Gastroenteritis (RV GE) Episodes. | GE episodes were defined as diarrhea (passage of three or more looser than normal stools within a day) with or without vomiting. RV GE episodes were defined as GE episodes for which the stool sample temporally closest to the onset day of the GE episode was positive for rotavirus by Enzyme Linked Immunosorbent Assay (ELISA). | Until Visit 4 (Week 17) for GE and until Visit 3 (Week 13) for RV GE. | 
| Number of Subjects Reporting Unsolicited Adverse Events (AEs). | 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 doses. | 
| Number of Subjects Reporting Any Serious Adverse Events (SAEs). | A serious adverse event (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. | Up to Visit 4. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Transmission, Gastroenteritis, Shedding, rotavirus, HRV vaccine