Phase III Study of Liquid Formulation of ROTAVIN

• Sponsor: Center for Research and Production of Vaccines and Biologicals, Vietnam (Other)
• Overall Status: Completed
• CT.gov ID: NCT03703336
• Collaborator: PATH (Other), National Institute of Hygiene and Epidemiology, Vietnam (Other), Children's Hospital Medical Center, Cincinnati (Other)
• Enrollment: 825
• Locations: 2
• Arms: 2
• Actual Duration (Months): 9.8
• Patients Per Site: 412.5
• Patients Per Site Per Month: 42.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diarrhea; Diarrhea Rotavirus	Biological: ROTAVIN (liquid formulation); Biological: ROTAVIN-M1 (frozen formulation)	Phase 3

Detailed Description

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 Design

• Study Type: Interventional
• Actual Enrollment: 825 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Eligible infants will be randomized to receive either ROTAVIN or ROTAVIN-M1 vaccines in the ratio of 2:1.Eligible infants will be randomized to receive either ROTAVIN or ROTAVIN-M1 vaccines in the ratio of 2:1.
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Phase III, Randomized, Partially Double- Blind, Active Control Study to Compare the Immunogenicity and Safety of a Liquid Formulation of ROTAVIN With the Currently Licensed Frozen Formulation of the Vaccine (ROTAVIN-M1), in Healthy Vietnamese Infants
• Actual Study Start Date: Mar 16, 2019
• Actual Primary Completion Date: Jan 8, 2020
• Actual Study Completion Date: Jan 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ROTAVIN Liquid Formulation Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Biological: ROTAVIN (liquid formulation); Live attenuated human rotavirus vaccine containing ≥ 2x10^6 plaque forming units (PFU) of strain G1P[8] per dose of 2 mL.
Active Comparator: ROTAVIN-M1 Frozen Formulation Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Biological: ROTAVIN-M1 (frozen formulation); Live attenuated human rotavirus vaccine containing ≥ 2x10^6 PFU of strain G1P[8] per dose of 2 mL.

Outcome Measures

Primary Outcome Measures

1. Geometric Mean Concentration (GMC) of Serum Anti-rotavirus Immunoglobulin A (IgA) Antibodies 28 Days After Second Vaccination [Day 85 (28 days after the 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.

2. Number of Participants With Solicited Reactions Within 7 Days of Vaccination [7 days after each vaccination (Days 1 to 8 and 57 to 64)]

   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.

Secondary Outcome Measures

1. Percentage of Participants With Seroconversion 28 Days After the Second Vaccination [28 days after the second vaccination (Day 85)]

   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.

2. Percentage of Participants With Seropositivity at Baseline and 28 Days After the Second Vaccination [Baseline (Day 1) and at 28 days after the second vaccination (Day 85)]

   Seropositivity is defined as serum IgA antibody concentration ≥ 20 U/mL

3. Number of Participants With Immediate Adverse Events (AEs) [Within 30 minutes after each vaccination on Day 1 and Day 57]

   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

4. Number of Participants With Unsolicited Adverse Events [From vaccination through 28 days after each dose (Days 1 to 28 and 57 to 85)]

   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.

5. Number of Participants With Serious Adverse Events Including Intussusception [From first vaccination through 28 days after the last vaccination; 85 days]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Days to 91 Days
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. Healthy infants as established by medical history and clinical examination before entering the study.

2. Age: 60-91 days (both days inclusive) at the time of enrollment.

3. Parental/legally acceptable representative ability and willingness to provide written informed consent.

4. Parent/legally acceptable representative who intends to remain in the area with the child during the study period.

Exclusion Criteria:

1. Presence of diarrhea or vomiting in the previous 72 hours or on the day of enrollment (temporary exclusion).

2. Presence of fever on the day of enrollment (temporary exclusion).

3. Acute disease at the time of enrollment (temporary exclusion).

4. Concurrent participation in another clinical trial at any point throughout the entire time frame for this study.

5. Presence of significant malnutrition (weight-for-height z-score < -3 SD median)

6. Presence of any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, hematological, endocrine, immunological, dermatological, neurological, cancer, or autoimmune disease) as determined by medical history and / or physical examination which would compromise the participant's health or is likely to result in nonconformance to the protocol.

7. History of congenital abdominal disorders, intussusception, or abdominal surgery.

8. Known or suspected impairment of immunological function based on medical history and physical examination.

9. Household contact with an immunosuppressed individual or pregnant woman.

10. Prior receipt of rotavirus or an intent to receive this vaccine from outside of the study center during study participation.

11. Prior receipt of Expanded Program on Immunization (EPI) vaccination during past 7 days or plan to receive them within next 7 days.

12. A known sensitivity or allergy to any components of the study vaccine.

13. History of allergy to antibiotic kanamycin.

14. Clinically detectable significant congenital or genetic defect.

15. History of persistent diarrhea (defined as diarrhea that lasts 14 days or longer).

16. Receipt of immunoglobulin therapy and / or blood products since birth or planned administration during the study period.

17. 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.

18. Any medical condition in the parent/legally acceptable representative or infant which, in the judgment of the Investigator, would interfere with or serves as a contraindication to protocol adherence.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	CDC Nam Dinh	Nam Dinh		Vietnam	10000
2	CDC Quang Ninh	Quang Ninh		Vietnam	10000

Sponsors and Collaborators

• Center for Research and Production of Vaccines and Biologicals, Vietnam
• PATH
• National Institute of Hygiene and Epidemiology, Vietnam
• Children's Hospital Medical Center, Cincinnati

Investigators

• Study Director: Niraj Rathi, MD, PATH India

Study Documents (Full-Text)

• Study Protocol - Jun 20, 2019
• Statistical Analysis Plan - Mar 12, 2020

More Information

Publications

None provided.

• Responsible Party: Center for Research and Production of Vaccines and Biologicals, Vietnam
• ClinicalTrials.gov Identifier: NCT03703336
• Other Study ID Numbers: CVIA 068; VX.2018.05
• First Posted: Oct 11, 2018
• Last Update Posted: Jan 25, 2021
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Center for Research and Production of Vaccines and Biologicals, Vietnam: ROTAVIN; Rotavirus vaccine; Rotavirus; Diarrhea
• Additional relevant MeSH terms: Diarrhea

Study Results

Participant Flow

Recruitment Details	This study was conducted by the National Institute of Hygiene and Epidemiology (NIHE) at 12 health centers in one district in the Nam Dinh province and at 12 health centers in one district in the Quang Ninh province in Vietnam.
Pre-assignment Detail	Infants were allocated to one of the two groups at a ratio of 2:1 to receive either the ROTAVIN liquid formulation or the frozen formulation ROTAVIN-M1.

Arm/Group Title	ROTAVIN Liquid Formulation	ROTAVIN-M1 Frozen Formulation
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.
Period Title: Overall Study
STARTED	552	273
Received Dose 1	552	273
Received Dose 2	518	263
Safety Population	551	274
COMPLETED	514	259
NOT COMPLETED	38	14

Baseline Characteristics

Arm/Group Title	ROTAVIN Liquid Formulation	ROTAVIN-M1 Frozen Formulation	Total
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Total of all reporting groups
Overall Participants	551	274	825
Age (days) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [days]	74.7 (8.63)	75.2 (9.15)	74.8 (8.81)
Sex: Female, Male (Count of Participants)
Female	276 50.1%	144 52.6%	420 50.9%
Male	275 49.9%	130 47.4%	405 49.1%
Race/Ethnicity, Customized (Count of Participants)
Vietnamese	551 100%	274 100%	825 100%
Province (Count of Participants)
Nam Dinh province	251 45.6%	124 45.3%	375 45.5%
Quang Ninh province	300 54.4%	150 54.7%	450 54.5%

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Concentration (GMC) of Serum Anti-rotavirus Immunoglobulin A (IgA) Antibodies 28 Days After Second Vaccination
Description	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)

Outcome Measure Data

Analysis Population Description

Immunogenicity assays were conducted on the subset of participants enrolled at Quang Ninh. The Per-Protocol (PP) population was defined as randomized participants who received a study vaccination, provided at least one evaluable serum sample, and who correctly received study vaccine per randomization with no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccines.

Arm/Group Title	ROTAVIN Liquid Formulation	ROTAVIN-M1 Frozen Formulation
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.
Measure Participants	267	135
Geometric Mean (95% Confidence Interval) [U/mL]	48.25	35.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ROTAVIN Liquid Formulation, ROTAVIN-M1 Frozen Formulation
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	If the lower limit of the 95% confidence interval (CI) of the ratio of GMCs between the ROTAVIN and ROTAVIN-M1 groups were to be larger than 1/2, ROTAVIN was considered to be non-inferior to the licensed frozen formulation of the vaccine (ROTAVIN-M1).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC Ratio
	Estimated Value	1.38
	Confidence Interval	(2-Sided) 95%; 1.02 to 1.86
	Parameter Dispersion	Type: Value:
	Estimation Comments	Log10-transformed IgA concentrations were used to construct a 2-sided 95% CI for the mean difference between the arms using t-distribution. The mean difference and 95% CI were exponentiated to obtain the GMC ratio and corresponding 95% CI.

2. Primary Outcome

Title	Number of Participants With Solicited Reactions Within 7 Days of Vaccination
Description	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)

Outcome Measure Data

Analysis Population Description

Safety population, as treated

Arm/Group Title	ROTAVIN Liquid Formulation	ROTAVIN-M1 Frozen Formulation
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.
Measure Participants	551	274
Any solicited reaction	195 35.4%	102 37.2%
Fever	37 6.7%	23 8.4%
Diarrhoea	57 10.3%	27 9.9%
Vomiting	78 14.2%	33 12%
Decreased appetite	68 12.3%	28 10.2%
Irritability	92 16.7%	48 17.5%
Decreased activity level	35 6.4%	23 8.4%
Mild severity	173 31.4%	85 31%
Moderate severity	61 11.1%	37 13.5%
Severe severity	22 4%	8 2.9%

3. Secondary Outcome

Title	Percentage of Participants With Seroconversion 28 Days After the Second Vaccination
Description	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)

Outcome Measure Data

Analysis Population Description

Immunogenicity assays were conducted on the subset of participants enrolled at Quang Ninh. The Per-Protocol (PP) population was defined as randomized participants who received a study vaccination, provided at least one evaluable serum sample, and who correctly received study vaccine per randomization with no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccines.

Arm/Group Title	ROTAVIN Liquid Formulation	ROTAVIN-M1 Frozen Formulation
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.
Measure Participants	267	135
Number (95% Confidence Interval) [percentage of participants]	70.4 12.8%	64.4 23.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ROTAVIN Liquid Formulation, ROTAVIN-M1 Frozen Formulation
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	6.0
	Confidence Interval	(2-Sided) 95%; -3.57 to 15.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With Seropositivity at Baseline and 28 Days After the Second Vaccination
Description	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)

Outcome Measure Data

Analysis Population Description

Immunogenicity assays were conducted on the subset of participants enrolled at Quang Ninh. The Per-Protocol (PP) population was defined as randomized participants who received a study vaccination, provided at least one evaluable serum sample, and who correctly received study vaccine per randomization with no major protocol deviations that were determined to potentially interfere with the immunogenicity assessment of the study vaccines.

Arm/Group Title	ROTAVIN Liquid Formulation	ROTAVIN-M1 Frozen Formulation
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.
Measure Participants	267	135
Day 1	0.4 0.1%	0.0 0%
Day 85	70.8 12.8%	64.4 23.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ROTAVIN Liquid Formulation, ROTAVIN-M1 Frozen Formulation
	Comments	Percentage Difference on Day 1
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	0.4
	Confidence Interval	(2-Sided) 95%; -2.40 to 2.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	ROTAVIN Liquid Formulation, ROTAVIN-M1 Frozen Formulation
	Comments	Percentage Difference on Day 85
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage Difference
	Estimated Value	6.3
	Confidence Interval	(2-Sided) 95%; -3.19 to 16.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Number of Participants With Immediate Adverse Events (AEs)
Description	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
Time Frame	Within 30 minutes after each vaccination on Day 1 and Day 57

Outcome Measure Data

Analysis Population Description

Safety population, as treated

Arm/Group Title	ROTAVIN Liquid Formulation	ROTAVIN-M1 Frozen Formulation
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.
Measure Participants	551	274
Any immediate adverse event	2 0.4%	0 0%
Immediate AEs occurring after dose 1	0 0%	0 0%
Immediate AEs occurring after dose 2	2 0.4%	0 0%
Vomiting	1 0.2%	0 0%
Pyrexia	1 0.2%	0 0%
Mild Immediate AEs	2 0.4%	0 0%
Moderate Immediate AEs	0 0%	0 0%
Severe Immediate AEs	0 0%	0 0%
Life-threatening Immediate AEs	0 0%	0 0%
Death	0 0%	0 0%

6. Secondary Outcome

Title	Number of Participants With Unsolicited Adverse Events
Description	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)

Outcome Measure Data

Analysis Population Description

Safety population, as treated

Arm/Group Title	ROTAVIN Liquid Formulation	ROTAVIN-M1 Frozen Formulation
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.
Measure Participants	551	274
Any unsolicited adverse events	292 53%	154 56.2%
Mild adverse events	191 34.7%	103 37.6%
Moderate adverse events	132 24%	63 23%
Severe adverse events	20 3.6%	10 3.6%
Life-threatening adverse events	0 0%	0 0%
Death	0 0%	0 0%
Related to study vaccine	2 0.4%	0 0%
Unrelated to study vaccine	291 52.8%	154 56.2%

7. Secondary Outcome

Title	Number of Participants With Serious Adverse Events Including Intussusception
Description	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

Outcome Measure Data

Analysis Population Description

Safety population, as treated

Arm/Group Title	ROTAVIN Liquid Formulation	ROTAVIN-M1 Frozen Formulation
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.	Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.
Measure Participants	551	274
Any serious adverse event	23 4.2%	14 5.1%
SAEs related to study vaccine	3 0.5%	3 1.1%
SAEs unrelated to study vaccine	20 3.6%	11 4%
Intussusception	0 0%	0 0%

Adverse Events

Time Frame	Serious adverse events and mortality are reported from the first vaccination date until 28 days after last dose; 85 days. Other adverse events are reported up to 28 days after each dose (Days 1-28 and 57 to 85)
Adverse Event Reporting Description	Safety population, as treated One participant was randomized to ROTAVIN but instead received ROTAVIN-M1 and was therefore analyzed in the ROTAVIN-M1 group for safety based on the actual treatment received.
Arm/Group Title	ROTAVIN Liquid Formulation		ROTAVIN-M1 Frozen Formulation
Arm/Group Description	Participants received two doses of ROTAVIN liquid formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.		Participants received two doses of ROTAVIN-M1 frozen formulation vaccine orally 8 weeks apart with the first dose administered at 60-91 days of age.
All Cause Mortality
	ROTAVIN Liquid Formulation		ROTAVIN-M1 Frozen Formulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/551 (0%)		0/274 (0%)
Serious Adverse Events
	ROTAVIN Liquid Formulation		ROTAVIN-M1 Frozen Formulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/551 (4.2%)		14/274 (5.1%)
Gastrointestinal disorders
Gastroenteritis	3/551 (0.5%)		5/274 (1.8%)
Enteritis	1/551 (0.2%)		1/274 (0.4%)
Aphthous ulcer	0/551 (0%)		1/274 (0.4%)
Diarrhoea	1/551 (0.2%)		0/274 (0%)
Diarrhoea infectious	1/551 (0.2%)		0/274 (0%)
Infections and infestations
Pneumonia	8/551 (1.5%)		3/274 (1.1%)
Urinary tract infection	1/551 (0.2%)		2/274 (0.7%)
Bronchiolitis	2/551 (0.4%)		0/274 (0%)
Bronchitis	2/551 (0.4%)		0/274 (0%)
Nasopharyngitis	2/551 (0.4%)		0/274 (0%)
Pertussis	1/551 (0.2%)		1/274 (0.4%)
Conjunctivitis	1/551 (0.2%)		0/274 (0%)
Otitis media acute	0/551 (0%)		1/274 (0.4%)
Skin and subcutaneous tissue disorders
Rash	2/551 (0.4%)		0/274 (0%)
Other (Not Including Serious) Adverse Events
	ROTAVIN Liquid Formulation		ROTAVIN-M1 Frozen Formulation
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	292/551 (53%)		154/274 (56.2%)
Blood and lymphatic system disorders
Lymphadenitis	2/551 (0.4%)		2/274 (0.7%)
Lymphadenopathy	1/551 (0.2%)		0/274 (0%)
Ear and labyrinth disorders
External ear inflammation	1/551 (0.2%)		0/274 (0%)
Eye disorders
Blepharitis	1/551 (0.2%)		0/274 (0%)
Eye pain	1/551 (0.2%)		0/274 (0%)
Gastrointestinal disorders
Diarrhoea	11/551 (2%)		6/274 (2.2%)
Dyspepsia	11/551 (2%)		0/274 (0%)
Vomiting	2/551 (0.4%)		1/274 (0.4%)
Diarrhoea infectious	2/551 (0.4%)		0/274 (0%)
Enteritis	0/551 (0%)		2/274 (0.7%)
Aphthous ulcer	0/551 (0%)		1/274 (0.4%)
Constipation	0/551 (0%)		1/274 (0.4%)
Gastroenteritis	1/551 (0.2%)		0/274 (0%)
Gastrointestinal infection	1/551 (0.2%)		0/274 (0%)
General disorders
Pyrexia	226/551 (41%)		112/274 (40.9%)
Vaccination site inflammation	0/551 (0%)		1/274 (0.4%)
Immune system disorders
Drug hypersensitivity	1/551 (0.2%)		0/274 (0%)
Hypersensitivity	0/551 (0%)		1/274 (0.4%)
Infections and infestations
Upper respiratory tract infection	22/551 (4%)		7/274 (2.6%)
Nasopharyngitis	12/551 (2.2%)		10/274 (3.6%)
Bronchitis	13/551 (2.4%)		7/274 (2.6%)
Pneumonia	8/551 (1.5%)		4/274 (1.5%)
Pharyngitis	4/551 (0.7%)		2/274 (0.7%)
Otitis media	2/551 (0.4%)		2/274 (0.7%)
Rhinitis	3/551 (0.5%)		1/274 (0.4%)
Bronchiolitis	3/551 (0.5%)		0/274 (0%)
Oral candidiasis	2/551 (0.4%)		1/274 (0.4%)
Otitis media acute	2/551 (0.4%)		1/274 (0.4%)
Conjunctivitis	1/551 (0.2%)		1/274 (0.4%)
Furuncle	1/551 (0.2%)		0/274 (0%)
Hordeolum	0/551 (0%)		1/274 (0.4%)
Influenza	0/551 (0%)		1/274 (0.4%)
Lymph node tuberculosis	0/551 (0%)		1/274 (0.4%)
Otitis externa	0/551 (0%)		1/274 (0.4%)
Pertussis	0/551 (0%)		1/274 (0.4%)
Pharyngitis bacterial	1/551 (0.2%)		0/274 (0%)
Roseola	0/551 (0%)		1/274 (0.4%)
Urinary tract infection	0/551 (0%)		1/274 (0.4%)
Respiratory, thoracic and mediastinal disorders
Cough	20/551 (3.6%)		9/274 (3.3%)
Rhinorrhoea	10/551 (1.8%)		3/274 (1.1%)
Oropharyngeal pain	5/551 (0.9%)		5/274 (1.8%)
Upper respiratory tract inflammation	4/551 (0.7%)		1/274 (0.4%)
Nasal congestion	2/551 (0.4%)		0/274 (0%)
Skin and subcutaneous tissue disorders
Rash	6/551 (1.1%)		2/274 (0.7%)
Dermatitis	0/551 (0%)		2/274 (0.7%)
Acne	0/551 (0%)		1/274 (0.4%)
Rash pruritic	0/551 (0%)		1/274 (0.4%)
Surgical and medical procedures
Nasal cavity packing	1/551 (0.2%)		0/274 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.