A Dose-escalating Study to Evaluate the Immunogenicity and Safety of Rotavin-M1 Vaccine in Healthy Infants

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of Rotavin-M1 produced by the Center for Research and Production of Vaccines and Biologicals (POLYVAC) in infants in Vietnam. In addition, we evaluate different dosages and schedules to determine the best regimen to test in a clinical trial.

Detailed Description
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Rotavirus (RV) is the most important cause of acute gastroenteritis in children worldwide. In Vietnam rotavirus causes an estimated 122,000-140,000 hospitalizations and 2900-5400 deaths per year among children under 5 years of age (1). Over the past 13 years, sentinel hospital surveillance identified rotavirus in 44%-62% of children admitted for the treatment of acute diarrhea in Vietnam (2-4). Such a high burden of disease justified accelerated development of a new and locally manufactured vaccine against rotavirus in Vietnam. It is estimated that if a vaccine was introduced in the current childhood immunization schedule, it could reduce severe rotavirus disease by about 60% or more given current vaccine efficacies and coverage (5). The Government of Vietnam has pursued a policy to encourage local vaccine production so the country could be self-reliant with affordable vaccines for its population (6). Over the past decades, several locally produced vaccines for poliomyelitis, cholera, Japanese encephalitis, and Diphtheria-Pertussis-Tetanus have contributed to the reduction in the prevalence of these diseases and to the eradication of polio over the past decade. While two commercial rotavirus vaccines, RotarixTM (GSK, Belgium) and RotaTeq® (Merck), have both been tested in Vietnam, neither is currently available at an affordable cost for the national program. Therefore, the candidate vaccine, Rotavin-M1, was developed in order to fill this need for a more affordable vaccine for Vietnamese children (6). This vaccine is similar to RotarixTM, and was developed by selecting a common G1P[8] strain and attenuating it through serial passages and plaque purification in qualified Vero cells under GLP conditions.

Official Title
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A Phase II, Randomized, Double-blind, Vaccine-controlled Dose-escalating Study to Evaluate the Immunogenicity, Reactogenicity and Safety of Oral Live Attenuated Human Rotavirus (HRV) Vaccine (Rotavin-M1) in Healthy Infants in Vietnam

Conditions
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Fever, Diarrhea, Nausea, Vomit, Irritability

Intervention / Treatment
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* Biological: Rotarix


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: At dose 1 A healthy male or female, 6 to 12 weeks of age (42 days to 84 days of age). Full term gestation (>=37 weeks). Birth weight of the subject should be >=2.5 kg. Healthy subjects as established by medical history and clinical examination before entering into the study. Did not use any dose of Rota virus vaccine. Written informed consent obtained from the parent or guardian of the subject. At dose 2 Received dose 1. Oral informed consent obtained from the parent or guardian of the subject for continuing participate the study. At dose 3 Received both dose 1 and dose 2. Oral informed consent obtained from the parent or guardian of the subject for continuing participate the study. Exclusion Criteria: At dose 1 Has a chronic disease (cardiovascular, liver, kidney disease). Acute disease at the time of enrolment. Administering corticosteroids (> 1mg/kg/day). Received any immunosuppressive therapy within 4 week before vaccination (Administration of immunoglobulins and/or any blood product or corticosteroids for >2 weeks). Immunosuppressive or immunodeficient condition. Family has immunosuppressive or immunodeficient condition medical history. History of high fever convulsion. Allergic or reaction with any component of vaccine, includes anaphylactic shock with any antibiotic. Preterm of gestation delivery (gestation period < 37 weeks). Low birth weight (<2.5 kg). Fever (axillary temperature >38oC) within 3 days before or on the day of vaccination. Malnutrition. Has any type of blood disorder, leukemia, or malignant tumor which can affect the bone marrow or lymph system. Use of any investigational or non-registered product (unlicensed 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. At dose 2 Acute disease at the time of 2nd dose. Administering corticosteroids (> 1mg/kg/day). Received any immunosuppressive therapy within 4 week before vaccination (Administration of immunoglobulins and/or any blood product or corticosteroids for >2 weeks). History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine. Fever (axillary temperature >38oC) within 3 days before or on the day of vaccination. Has any type of blood disorder, leukemia, or malignant tumor which can affect the bone marrow or lymph system. Use of any investigational or non-registered product (unlicensed drug or vaccine) other than the study vaccine during the study period. At dose 3 Acute disease at the time of 3rd dose. Administering corticosteroids (> 1mg/kg/day). Received any immunosuppressive therapy within 4 week before vaccination (Administration of immunoglobulins and/or any blood product or corticosteroids for >2 weeks). History of allergic disease or reactions likely to be exacerbated by any component of the study vaccine. Fever (axillary temperature >38oC) within 3 days before or on the day of vaccination. Has any type of blood disorder, leukemia, or malignant tumor which can affect the bone marrow or lymph system. Use of any investigational or non-registered product (unlicensed drug or vaccine) other than the study vaccine during the study period.

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

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Rotavin2H<br>2 doses of Rotavin-M1 vaccine, 106.3FFU/dose, 2-month separation between doses | Biological: Rotarix<br>* 2 doses of Rotarix vaccine, 106.5CID/dose, 1-month interval between doses<br>* Other names: RotarixTM, GSK biologicals;|
| Experimental: Rotavin2L<br>2 doses of Rotavin-M1 vaccine, 106.0FFU/dose, 2-month interval between doses | Biological: Rotarix<br>* 2 doses of Rotarix vaccine, 106.5CID/dose, 1-month interval between doses<br>* Other names: RotarixTM, GSK biologicals;|
| Experimental: Rotavin3H<br>3 doses of Rotavin-M1 vaccine, 106.3FFU/dose, 1-month interval between doses | Biological: Rotarix<br>* 2 doses of Rotarix vaccine, 106.5CID/dose, 1-month interval between doses<br>* Other names: RotarixTM, GSK biologicals;|
| Experimental: Rotavin3L<br>3 doses of Rotavin-M1, 106.0FFU/dose, 1-month interval between doses | Biological: Rotarix<br>* 2 doses of Rotarix vaccine, 106.5CID/dose, 1-month interval between doses<br>* Other names: RotarixTM, GSK biologicals;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess immunogenicity of a new rotavirus vaccine Rotavin-M1 in terms of anti-rotavirus IgA antibody seroconversion 1 month after complete the vaccination schedule | To assess immunogenicity of Rotavin-M1 of 2 titers (10e6.0 and 10e6.3FFU/dose) and 2 schedules (3 doses and 1-month interval between vs 2 doses and 2-month interval between doses), compared with 2 doses GSK's lyophilized Rotarix (10e6.5 CID50/dose). | up to 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To assess immunogenicity of Rotavin-M1 vaccine versus GSK Biologicals' HRV vaccine in terms of anti-rotavirus IgA antibody seroconversion at Month 2 in the group receiving the vaccines. | To assess immunogenicity of Rotavin-M1 vaccine (of different dosages and schedules) versus GSK Biologicals' HRV vaccine in terms of anti-rotavirus IgA antibody seroconversion at Month 2 in the group receiving the vaccines. | up to 7 months | 
| To assess immunogenicity of Rotavin-M1 vaccine versus GSK Biologicals' HRV vaccine in terms of anti-rotavirus IgA antibody GMT at Month 2 in the group receiving the vaccines. | To assess immunogenicity of Rotavin-M1 vaccine (of different dosages and schedules) versus GSK Biologicals' HRV vaccine in terms of anti-rotavirus IgA antibody GMT at Month 2 in the group receiving the vaccines. | up to 7 months | 
| To assess immunogenicity of Rotavin-M1 vaccine versus GSK Biologicals' HRV vaccine in terms of anti-rotavirus IgA antibody GMT at Month 3 in the group receiving the vaccines. | To assess immunogenicity of Rotavin-M1 vaccine (of different dosages and schedules) versus GSK Biologicals' HRV vaccine in terms of anti-rotavirus IgA antibody GMT at Month 3 in the group receiving the vaccines. | up to 7 months | 
| To assess the safety and reactogenicity of each dose of Rotavin-M1 versus GSK's biologicals Rotarix | To assess immediate reactions (30minutes) after administration of each dose To assess adverse events 30 days after each dose To assess change in blood cell counts (red blood cells, white blood cells, platelets), blood urea nitrogen concentration, transaminase concentration (ALT, AST) | up to 7 months | 
| To assess the presence of rotavirus (RV) in GE stools collected after administration of first dose of the study vaccine up to 1 month after the last dose. | To assess the presence of rotavirus (RV) in GE stools collected after administration of the first dose of the study vaccine up to 1 month after the last dose. | up to 7 months | 
| To assess the shedding of rotavirus (RV) in stools collected daily for 7 days after administration of each dose of the study vaccine. | To assess the shedding of rotavirus (RV) in stools collected daily for 7 days after administration of each dose of the study vaccine | up to 7 months | 
| To compare the RV antibody titers 1 year after the first doses between one Rotavin-M1 group and Rotarix | To assess the RV antibody titers 1 year after the 1st dose between Rotavin-M1 group (106.3FFU/dose, 2 doses, 2-month interval) and Rotarix group (106.0CID/dose, 2 doses, 1-month interval between doses). | up to 15 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diarrhea, fever, nausea, vomit, irritability