Phase III Study on Rotavirus Vaccine to Evaluate Lot-to-lot Consistency and Interference With Routine UIP Immunization

Study Overview
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Brief Summary
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This is a Phase 3, open-label, randomized study to evaluate lot-to-lot consistency in the manufacture of Bovine Rotavirus Pentavalent Vaccine (BRV-PV).

Detailed Description
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The study is designed to evaluate lot-to-lot consistency in the manufacturing of Rotavirus vaccine by testing the vaccine in infants in order to demonstrate equivalence in the induction of specific anti-rotavirus IgA antibodies across three production lots. The study will also examine the potential interference of vaccine with UIP vaccines that will be administered concurrently by assessing non-inferiority in the immune responses to those vaccines when administered with / without the study vaccine.

Official Title
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A Phase III, Multicenter, Open Label, Randomized Study of Bovine Rotavirus Pentavalent Vaccine (BRV-PV) to Evaluate Lot-To-Lot Consistency and to Investigate Potential Interference With Routine UIP Vaccinations in Healthy Infants in India.

Conditions
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Rotavirus Gastroenteritis

Intervention / Treatment
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* Biological: BRV-PV Lot A + DPT-HepB-Hib + OPV
* Biological: BRV-PV Lot B + DPT-HepB-Hib + OPV
* Biological: BRV-PV Lot C + DPT-HepB-Hib + OPV
* Biological: ROTARIX + DPT-HepB-Hib + OPV


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy infants as established by medical history and clinical examination before entering the study. Age: 6-8 weeks at the time of enrollment. Parental ability and willingness to provide written informed consent. Parent who intends to remain in the area with the child during the study period. Receipt of birth dose of Hepatitis B vaccine and OPV. Exclusion Criteria: Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment (temporary exclusion). Presence of fever on the day of enrollment (temporary exclusion). Acute disease at the time of enrollment (temporary exclusion). Concurrent participation in another clinical trial at any point throughout the entire timeframe for this study. Presence of significant malnutrition or any systemic disorder as determined by medical history and / or physical examination which would compromise the subject's health or is likely to result in nonconformance to the protocol. History of congenital abdominal disorders, intussusception, or abdominal surgery. Known or suspected impairment of immunological function based on medical history and physical examination. Household contact with an immunosuppressed individual or pregnant woman. Prior receipt or intent to receive rotavirus and / or diphtheria, tetanus, pertussis, Haemophilus Influenzae type b, Hepatitis B vaccine (other than birth dose) or inactivated polio vaccine (IPV) during the study period and outside of the study. OPV dose received during national / subnational immunization days will be allowed. A known sensitivity or allergy to any components of the study vaccine. Clinically detectable congenital or genetic defect. History of persistent diarrhea (defined as diarrhea that lasts 14 days or longer). Receipt of any immunoglobulin therapy and / or blood products since birth or planned administration during the study period. History of chronic administration (defined as more than 14 days) of immunosuppressants including corticosteroids. Infants on inhaled or topical steroids may be permitted to participate in the study. History of any neurologic disorders or seizures. Any medical condition in the parents / infant which, in the judgment of the Investigator, would interfere with or serves as a contraindication to protocol adherence or a participant's parents' ability to give written informed consent.

Ages Eligible for Study
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Minimum Age: 6 Weeks
Maximum Age: 8 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 - BRV-PV Lot A<br>BRV-PV Lot A + DPT- HepB-Hib + OPV | Biological: BRV-PV Lot A + DPT-HepB-Hib + OPV<br>* Dose 1: 6-8 weeks, Dose 2: 10 week, Dose 3: 14 week<br>|
| Experimental: Group 2 - BRV-PV Lot B<br>BRV-PV Lot B+ DPT- HepB-Hib + OPV | Biological: BRV-PV Lot B + DPT-HepB-Hib + OPV<br>* Dose 1: 6-8 weeks, Dose 2: 10 week, Dose 3: 14 week<br>* Other names: Live Attenuated human-bovine reassortant pentavalent rotavirus vaccine;|
| Experimental: Group 3 - BRV-PV Lot C<br>BRV-PV Lot C + DPT- HepB-Hib + OPV | Biological: BRV-PV Lot C + DPT-HepB-Hib + OPV<br>* Dose 1: 6-8 weeks, Dose 2: 10 week, Dose 3: 14 week<br>|
| Active Comparator: Group 4 - ROTARIX<br>ROTARIX + DPT-HepB-Hib + OPV | Biological: ROTARIX + DPT-HepB-Hib + OPV<br>* Dose 1: 6-8 weeks, Dose 2: 10 week, Dose 3: 14 week (Third dose-Placebo)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rotavirus vaccine lots Immunogenicity | Serum anti- rotavirus IgA antibody concentrations expressed as GMCs for the BRV-PV to demonstrate equivalence in lot consistency among three lots. | Four weeks after the third dose of vaccination | 
| Immunogenicity of UIP vaccines |  | Four weeks after the third dose of vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immediate adverse events and Solicited post -vaccination reactogenicity |  | AEs within 30 minutes post-vaccination and post vacc reactogenicity during 7 days after each vaccination | 
| Rotavirus Immunogenicity: | Serum anti- rotavirus IgA antibody concentrations expressed as GMCs and proportion of subjects with post-vaccination IgA antibody concentration ≥20 U/ml for the comparison of BRV-PV vaccine and licensed rotavirus vaccine. | Four weeks after the third dose of vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BRV-PV, Rotavirus vaccine, lot-to-lot consistency, interference with routine immunization