Vaccine Efficacy Against Rotavirus Diarrhea; Vaccine Given With Routine Childhood Vaccinations in Healthy African Infants

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT00241644

First received: October 18, 2005

Last updated: April 11, 2013

Last verified: November 2012

History of Changes

Results First Received: June 18, 2009

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Prevention
Condition:	Rotavirus Vaccines
Interventions:	Biological: Rotarix™ Biological: Placebo

Participant Flow

Hide Participant Flow

Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Only subjects from Malawi and from Cohort 2 South Africa were asked to continue the study for a second follow-up period (Year 2).

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Of the total of 4941 subjects enrolled in this study, 2 subjects were allocated a subject number but did not get any study vaccine administered. Hence, only 4939 subjects were considered as 'started'. For the second follow-up period, as mentioned in the protocol the results are presented for Rotarix Pooled and Placebo Groups only.

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

Of the total of 4941 subjects enrolled in this study, 2 subjects were allocated a subject number but did not get any study vaccine administered. Hence, only 4939 subjects were considered as 'started'.

For the second follow-up period, as mentioned in the protocol the results are presented for Rotarix Pooled and Placebo Groups only.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Placebo Group	Subjects received 3 doses of placebo.
Rotarix Pooled Group	Subjects received 2 or 3 doses of Rotarix™ (rotavirus vaccine).

Participant Flow for 2 periods

Period 1: First Efficacy Period (Year 1)

	Rotarix 2-dose Group	Rotarix 3-dose Group	Placebo Group	Rotarix Pooled Group
STARTED	1647	1651	1641	3298
COMPLETED	1420	1383	1392	2803
NOT COMPLETED	227	268	249	495
Adverse Event	46	45	45	91
Protocol Violation	3	5	4	8
Withdrawal by Subject	59	74	81	133
Lost to Follow-up	116	142	116	258
Non-compliance	2	1	2	3
Return dates not reliable	1	0	0	1
Vaccinated at regular clinic	0	0	1	0
Subject's parent passed away	0	1	0	1

Period 2: Second Efficacy Period (Year 2)

	Rotarix 2-dose Group	Rotarix 3-dose Group	Placebo Group	Rotarix Pooled Group
STARTED	771	754	746	1525
COMPLETED	710	697	682	1407
NOT COMPLETED	61	57	64	118
Adverse Event	11	9	12	20
Protocol Violation	2	1	2	3
Withdrawal by Subject	4	3	2	7
Lost to Follow-up	43	43	46	86
Consenting parent passed away	1	1	2	2

Baseline Characteristics

Hide Baseline Characteristics

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Placebo Group	Subjects received 3 doses of placebo.
Rotarix Pooled Group	Subjects received 2 or 3 doses of Rotarix™ (rotavirus vaccine).
Total	Total of all reporting groups

Baseline Measures

	Rotarix 2-dose Group	Rotarix 3-dose Group	Placebo Group	Rotarix Pooled Group	Total
Number of Participants [units: participants]	1647	1651	1641	3298	8237
Age [units: weeks] Mean ± Standard Deviation	6.3 ± 0.92	6.4 ± 0.98	6.4 ± 0.97	6.4 ± 0.95	6.4 ± 0.95
Gender [units: subjects]
Female	811	839	800	1650	4100
Male	836	812	841	1648	4137

Outcome Measures

Hide All Outcome Measures

1. Primary:

Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain [ Time Frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age ]

Measure Type	Primary
Measure Title	Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain
Measure Description	Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time Frame	From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the According-to-Protocol (ATP) cohort for efficacy

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1496	1478	2974	1443
Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain [units: subjects]	30	26	56	70

No statistical analysis provided for Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain

2. Secondary:

Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type [ Time Frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age ]

Measure Type	Secondary
Measure Title	Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type
Measure Description	Number of subjects presenting with three or more looser than normal stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. Rotavirus types were G1 wild type (WT) and non-G1.
Time Frame	From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ATP cohort for efficacy

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1496	1478	2974	1443
Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type [units: subjects]
G1 WT	8	9	17	23
Non-G1	22	17	39	47

No statistical analysis provided for Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain, Classified by Rotavirus Type

3. Secondary:

Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain [ Time Frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age ]

Measure Type	Secondary
Measure Title	Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain
Measure Description	Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample.
Time Frame	From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ATP cohort for efficacy

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1496	1478	2974	1443
Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain [units: subjects]	93	74	167	174

No statistical analysis provided for Number of Subjects Reporting Any Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain

4. Secondary:

Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain [ Time Frame: From the first vaccine or placebo dose up to 1 year of age ]

Measure Type	Secondary
Measure Title	Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain
Measure Description	Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time Frame	From the first vaccine or placebo dose up to 1 year of age
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1647	1651	3298	1641
Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain [units: subjects]	37	31	68	83

No statistical analysis provided for Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain

5. Secondary:

In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain [ Time Frame: From 2 weeks after the third dose of vaccine or placebo up to 1 year of age ]

Measure Type	Secondary
Measure Title	In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain
Measure Description	Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time Frame	From 2 weeks after the third dose of vaccine or placebo up to 1 year of age
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ATP cohort for efficacy, only for the subset of subjects in South Africa who were fully vaccinated before the beginning of the rotavirus season. For this analysis, data from Rotarix 2-dose Group and Rotarix 3-dose Group were pooled into one group (Rotarix pooled Group).

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.

Analysis was performed on the ATP cohort for efficacy, only for the subset of subjects in South Africa who were fully vaccinated before the beginning of the rotavirus season.

For this analysis, data from Rotarix 2-dose Group and Rotarix 3-dose Group were pooled into one group (Rotarix pooled Group).

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	478	468	946	468
In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain [units: subjects]	5	3	8	20

No statistical analysis provided for In South Africa, Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strain

6. Secondary:

Number of Subjects Reporting Severe Gastroenteritis of Any Cause [ Time Frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age ]

Measure Type	Secondary
Measure Title	Number of Subjects Reporting Severe Gastroenteritis of Any Cause
Measure Description	Number of subjects with gastroenteritis (three or more looser than normal stools or watery stools within a day) that scored ≥ 11 on the 20-point Vesikari scoring system.
Time Frame	From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ATP cohort for efficacy.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1496	1478	2974	1443
Number of Subjects Reporting Severe Gastroenteritis of Any Cause [units: subjects]	134	122	256	178

No statistical analysis provided for Number of Subjects Reporting Severe Gastroenteritis of Any Cause

7. Secondary:

Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain [ Time Frame: From 2 weeks after the last vaccine or placebo dose up to 1 year of age ]

Measure Type	Secondary
Measure Title	Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain
Measure Description	RV GE caused by the circulating wild-type rotavirus strain: three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample collected as soon as possible after the symptoms begin.
Time Frame	From 2 weeks after the last vaccine or placebo dose up to 1 year of age
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ATP cohort for efficacy

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1496	1478	2974	1443
Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain [units: subjects]	78	64	142	156

No statistical analysis provided for Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strain

8. Secondary:

For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains [ Time Frame: During the period from 2 weeks after the last dose of vaccine or placebo until study end ]

Measure Type	Secondary
Measure Title	For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains
Measure Description	Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time Frame	During the period from 2 weeks after the last dose of vaccine or placebo until study end
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed on the According-To-Protocol (ATP) cohort for efficacy of the combined efficacy follow-up periods.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	0	0	1873	891
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains [units: subjects]			81	66

No statistical analysis provided for For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains

9. Secondary:

Measure Type	Secondary
Measure Title	For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains
Measure Description	Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system.
Time Frame	During the period from 1 year of age to study end
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed on the According-To-Protocol (ATP) cohort for efficacy of the second efficacy period.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	0	0	1500	712
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis (RV GE) Caused by the Circulating Wild-type Rotavirus Strains [units: subjects]			35	21

10. Secondary:

For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains [ Time Frame: During the period from 2 weeks after the last dose of vaccine or placebo until study end ]

Measure Type	Secondary
Measure Title	For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains
Measure Description	RV GE caused by the circulating wild-type rotavirus strain: three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample collected as soon as possible after the symptoms begin.
Time Frame	During the period from 2 weeks after the last dose of vaccine or placebo until study end
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed on the ATP cohort for efficacy of the combined efficacy follow-up periods.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	0	0	1873	891
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains [units: subjects]			159	118

No statistical analysis provided for For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains

11. Secondary:

Measure Type	Secondary
Measure Title	For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains
Measure Description	RV GE caused by the circulating wild-type rotavirus strain: three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample collected as soon as possible after the symptoms begin.
Time Frame	During the period from 1 year of age to study end
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed on the ATP cohort for efficacy of the second efficacy period.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	0	0	1500	712
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects Hospitalized and/or With Supervised Re-hydration Therapy Due to Rotavirus Gastroenteritis (RV GE) Episode Caused by the Circulating Wild-type RV Strains [units: subjects]			58	26

12. Secondary:

For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type [ Time Frame: During the period from 2 weeks after the last dose of vaccine or placebo until study end ]

Measure Type	Secondary
Measure Title	For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type
Measure Description	Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. Rotavirus types were G1 wild type (WT) and non-G1.
Time Frame	During the period from 2 weeks after the last dose of vaccine or placebo until study end
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed on the ATP cohort for efficacy of the combined efficacy follow-up periods.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	0	0	1873	891
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type [units: subjects]
G1 WT			21	20
Non-G1			60	48

No statistical analysis provided for For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type

13. Secondary:

Measure Type	Secondary
Measure Title	For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type
Measure Description	Number of subjects presenting with three or more looser than normal stools or watery stools within a day, occurring after administration of dose 1 of study vaccine in which rotavirus other than vaccine strain was identified in a stool sample with a score ≥ 11 on the 20-point Vesikari scoring system. Rotavirus types were G1 wild type (WT) and non-G1.
Time Frame	During the period from 1 year of age to study end
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
The analysis was performed on the ATP cohort for efficacy of the second efficacy period.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	0	0	1500	712
For Subjects in Cohort 2 South Africa and the Cohort in Malawi: Number of Subjects With Severe Rotavirus Gastroenteritis Caused by the Circulating Wild-type Rotavirus Strains, Classified by Rotavirus Type [units: subjects]
G1 WT			10	11
Non-G1			25	10

14. Secondary:

Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out [ Time Frame: From the first dose of vaccine or placebo up to end of the study ]

Measure Type	Secondary
Measure Title	Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out
Measure Description	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. An 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.
Time Frame	From the first dose of vaccine or placebo up to end of the study
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1647	1651	3298	1641
Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out [units: subjects]	57	54	111	56

No statistical analysis provided for Number of Subjects With Adverse Events (AEs) or Serious Adverse Events (SAEs) Leading to Drop Out

15. Secondary:

Number of Subjects Reporting Serious Adverse Events (SAEs) [ Time Frame: From the first dose of vaccine or placebo up to end of the study ]

Measure Type	Secondary
Measure Title	Number of Subjects Reporting Serious Adverse Events (SAEs)
Measure Description	An 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.
Time Frame	From the first dose of vaccine or placebo up to end of the study
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1647	1651	3298	1641
Number of Subjects Reporting Serious Adverse Events (SAEs) [units: subjects]	222	199	421	246

No statistical analysis provided for Number of Subjects Reporting Serious Adverse Events (SAEs)

16. Secondary:

Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects [ Time Frame: One month after the last vaccine dose ]

Measure Type	Secondary
Measure Title	Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects
Measure Description	An initially seronegative subject is a subject whose IgA antibody concentration was below the assay cut-off value of 20 Units per milliliter (U/mL) before administration of the first vaccine dose.
Time Frame	One month after the last vaccine dose
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ATP cohort for immunogenicity, only for initially seronegative subjects.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	106	115	221	111
Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects [units: Units per milliliter (U/mL)] Geometric Mean ( 95% Confidence Interval )	56.6 ( 38.9 to 82.3 )	79.4 ( 54.7 to 115.2 )	67.5 ( 51.9 to 87.8 )	23.4 ( 16.8 to 32.5 )

No statistical analysis provided for Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies in Initially Seronegative Subjects

17. Secondary:

Number of Seroconverted Subjects [ Time Frame: One month after the last vaccine or placebo dose ]

Measure Type	Secondary
Measure Title	Number of Seroconverted Subjects
Measure Description	Seroconverted subjects are defined as subjects with appearance of anti-rotavirus IgA antibody concentration ≥ 20 U/mL in subjects initially (i.e. prior to the first dose of vaccine or placebo) seronegative for rotavirus.
Time Frame	One month after the last vaccine or placebo dose
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ATP cohort for immunogenicity, only for inititally seronegative subjects.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	106	115	221	111
Number of Seroconverted Subjects [units: subjects]	57	72	129	25

No statistical analysis provided for Number of Seroconverted Subjects

18. Secondary:

Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies [ Time Frame: One month after the last vaccine or placebo dose ]

Measure Type	Secondary
Measure Title	Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies
Measure Description	Geometric mean concentrations are given as Units per milliliter (U/mL).
Time Frame	One month after the last vaccine or placebo dose
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ATP cohort for immunogenicity.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1160	1138	2298	1125
Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies [units: U/mL] Geometric Mean ( 95% Confidence Interval )	72.5 ( 65.2 to 80.6 )	67.9 ( 60.8 to 75.9 )	70.2 ( 65.0 to 75.8 )	21.8 ( 19.8 to 24.0 )

No statistical analysis provided for Geometric Mean Concentration of Anti-rotavirus Immunoglobulin A (IgA) Antibodies

19. Secondary:

Number of Seropositive Subjects [ Time Frame: One month after the last vaccine or placebo dose ]

Measure Type	Secondary
Measure Title	Number of Seropositive Subjects
Measure Description	Seropositive subjects are defined as subjects with anti-rotavirus IgA antibody concentration ≥ 20 U/mL.
Time Frame	One month after the last vaccine or placebo dose
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Analysis was performed on the ATP cohort for immunogenicity.

Reporting Groups

	Description
Rotarix 2-dose Group	Subjects received 1 dose of placebo followed by 2 doses of Rotarix™ (rotavirus vaccine).
Rotarix 3-dose Group	Subjects received 3 doses of Rotarix™ (rotavirus vaccine).
Rotarix Pooled Group	For some data analyses, the 2 Groups receiving Rotarix (Rotarix 2-dose Group & Rotarix 3-dose Group) were pooled into Rotarix pooled Group.
Placebo Group	Subjects received 3 doses of placebo.

Measured Values

	Rotarix 2-dose Group	Rotarix 3-dose Group	Rotarix Pooled Group	Placebo Group
Number of Participants Analyzed [units: participants]	1160	1138	2298	1125
Number of Seropositive Subjects [units: subjects]	756	706	1462	262

No statistical analysis provided for Number of Seropositive Subjects

Serious Adverse Events

Show Serious Adverse Events

Other Adverse Events

Show Other Adverse Events

More Information

Hide More Information

Certain Agreements:

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

There IS 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.

The agreement is:

	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: GSK Response Center
Organization: GlaxoSmithKline
phone: 866-435-7343

Publications:

Madhi SA, Cunliffe NA, Steele D, Witte D, Kirsten M, Louw C, Ngwira B, Victor JC, Gillard PH, Cheuvart BB, Han HH, Neuzil KM. Effect of human rotavirus vaccine on severe diarrhea in African infants. N Engl J Med. 2010 Jan 28;362(4):289-98.

Publications automatically indexed to this study:

Steele AD, Neuzil KM, Cunliffe NA, Madhi SA, Bos P, Ngwira B, Witte D, Todd S, Louw C, Kirsten M, Aspinall S, Van Doorn LJ, Bouckenooghe A, Suryakiran PV, Han HH. Human rotavirus vaccine Rotarix™ provides protection against diverse circulating rotavirus strains in African infants: a randomized controlled trial. BMC Infect Dis. 2012 Sep 13;12:213. doi: 10.1186/1471-2334-12-213.

Responsible Party:	GlaxoSmithKline
ClinicalTrials.gov Identifier:	NCT00241644 History of Changes
Obsolete Identifiers:	NCT00598468
Other Study ID Numbers:	102248
Study First Received:	October 18, 2005
Results First Received:	June 18, 2009
Last Updated:	April 11, 2013
Health Authority:	South Africa: Medicines Control Council

To Top