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

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
Conditions:	Gastroenteritis Caused by Rotavirus Prophylaxis Rotavirus
Interventions:	Biological: Rotarix™ Biological: Placebo

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

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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).

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

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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

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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 ]

Show Outcome Measure 8

9. 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 1 year of age to study end ]

Show Outcome Measure 9

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 ]

Show Outcome Measure 10

11. 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 1 year of age to study end ]

Show Outcome Measure 11

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 ]

Show Outcome Measure 12

13. 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 1 year of age to study end ]

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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 ]

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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 ]

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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 ]

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17. Secondary:

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

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18. Secondary:

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

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19. Secondary:

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

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Serious Adverse Events

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Other Adverse Events

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More Information

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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
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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.

Responsible Party:	Cheri Hudson; Clinical Disclosure Advisor, GSK Clinical Disclosure
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:	February 9, 2012
Health Authority:	South Africa: Medicines Control Council