This study is conducted to demonstrate non-inferiority in the immunogenicity of the liquid formulation of ROTAVIN in comparison to currently licensed frozen formulation of the vaccine (ROTAVIN-M1), 28 days after the second vaccination when administered as two dose series starting at 2-3 months of age. The study will also assess the reactogenicity of the vaccine 7 days after each vaccination and safety from first vaccination up to 4 weeks after the last vaccination.
The study is designed as a phase III, randomized, partially double-blinded, active controlled study with two groups of infants receiving vaccines at the ratio of 2:1 (liquid formulation of ROTAVIN to frozen formulation ROTAVIN-M1), to compare their immunogenicity and safety. Two doses of vaccine will be administered 8 weeks apart with the first vaccine administration between 60-91 days of age. All childhood vaccines as per the Expanded Program for Immunization of the Government of Vietnam (including Diphtheria, Tetanus, Pertussis, Haemophilus influenzae type b and Hepatitis B vaccine (DTwPHib-HepB), and Oral Polio Vaccine at at 2, 3 and 4 months of age) will be allowed as per the immunization schedule. Active surveillance for vaccine reactogenicity (solicited reactions) over the 7-day period after each vaccination, unsolicited adverse events (AEs) for 4 weeks after each vaccination and serious adverse events (SAEs) including intussusception over the period between first vaccination and four weeks after the last vaccination will be conducted for all infants. This trial will generate immunogenicity and safety data which would be submitted to Ministry of Health in Vietnam for license of new formulation of ROTAVIN vaccine.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
825
Live attenuated human rotavirus vaccine containing ≥ 2x10\^6 plaque forming units (PFU) of strain G1P\[8\] per dose of 2 mL.
Live attenuated human rotavirus vaccine containing ≥ 2x10\^6 PFU of strain G1P\[8\] per dose of 2 mL.
CDC Nam Dinh
Nam Định, Vietnam
CDC Quang Ninh
Quang Ninh, Vietnam
Geometric Mean Concentration (GMC) of Serum Anti-rotavirus Immunoglobulin A (IgA) Antibodies 28 Days After Second Vaccination
Serum anti-rotavirus IgA antibodies were measured using a validated enzyme linked immunosorbent assay (ELISA) at the Cincinnati Children's Hospital Medical Center (CCHMC), Division of Infectious Diseases in Cincinnati, Ohio USA.
Time frame: Day 85 (28 days after the second vaccination)
Number of Participants With Solicited Reactions Within 7 Days of Vaccination
Solicited post-vaccination reactogenicity included fever, diarrhea, vomiting, decreased appetite, irritability, and decreased activity level during the seven-day period after each vaccination. Parents were asked to record reactions on a post-immunization diary card. Solicited reactions were graded for severity on a scale from mild to severe based on the level of symptoms.
Time frame: 7 days after each vaccination (Days 1 to 8 and 57 to 64)
Percentage of Participants With Seroconversion 28 Days After the Second Vaccination
Seroconversion is defined as a post-vaccination serum anti-rotavirus IgA antibody concentration of at least 20 U/mL if the baseline concentration was \< 20 U/mL or a post- vaccination serum anti-rotavirus IgA antibody concentration of ≥ 4-fold baseline level if the baseline concentration was ≥ 20 U/mL.
Time frame: 28 days after the second vaccination (Day 85)
Percentage of Participants With Seropositivity at Baseline and 28 Days After the Second Vaccination
Seropositivity is defined as serum IgA antibody concentration ≥ 20 U/mL
Time frame: Baseline (Day 1) and at 28 days after the second vaccination (Day 85)
Number of Participants With Immediate Adverse Events (AEs)
After each vaccination participants were observed at the clinic site for at least 30 minutes to check for any immediate AEs including episodes of vomiting and allergic reaction to vaccine. Immediate AEs include all reactions that occurred within 30 minutes of each vaccination. Reactions were graded for severity per the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, version 2.1, of the US National Institute of Health: Grade 1: Mild symptoms causing no or minimal interference with usual social \& functional activities; intervention not indicated. Grade 2: Moderate symptoms causing greater than minimal interference with usual activities; intervention indicated. Grade 3: Severe symptoms causing inability to perform usual activities; intervention or hospitalization indicated. Grade 4: Potentially life-threatening symptoms; intervention indicated to prevent permanent impairment, persistent disability, or death Grade 5: Death
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Time frame: Within 30 minutes after each vaccination on Day 1 and Day 57
Number of Participants With Unsolicited Adverse Events
An unsolicited AE was any AE that occurred after vaccination, whether or not deemed "related" to the product, that was not solicited, or, any solicited reaction that started after 7 days post-vaccination. Severity of unsolicited AEs was graded per the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, version 2.1. Grade 1: Mild symptoms causing no or minimal interference with usual social \& functional activities; intervention not indicated Grade 2: Moderate symptoms causing greater than minimal interference with usual activities; intervention indicated Grade 3: Severe symptoms causing inability to perform usual activities; intervention or hospitalization indicated Grade 4: Potentially life-threatening symptoms; intervention indicated to prevent permanent impairment, persistent disability, or death Grade 5: Death The clinician classified the causality of each AE as related if there was reasonable possibility that the product caused the event.
Time frame: From vaccination through 28 days after each dose (Days 1 to 28 and 57 to 85)
Number of Participants With Serious Adverse Events Including Intussusception
All Serious adverse events (SAEs), including cases of intussusception, were recorded at all time points between first vaccination and last visit. An SAE was defined as any untoward medical occurrence that: * Resulted in death, * Was life threatening, * Required inpatient hospitalization or prolongation of existing hospitalization, * Resulted in persistent or significant disability / incapacity, * Was a congenital anomaly or a birth defect, * Medically important event Investigator-confirmed cases of intussusception also qualified as an SAE in this study. Intussusception is the infolding (telescoping) of one segment of the intestine within another, usually resulting in a blockage of the intestine.
Time frame: From first vaccination through 28 days after the last vaccination; 85 days