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Developing World Study for RotaTeq™ (V260-015)(COMPLETED)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00362648
First received: August 8, 2006
Last updated: November 3, 2014
Last verified: November 2014
Results First Received: March 11, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Conditions: Vomiting
Diarrhea
Fever
Interventions: Biological: RotaTeq™ - Rotavirus Vaccine, Live, Oral, Pentavalent
Biological: Comparator: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

The study was conducted at 5 international sites – Ghana, Kenya, Mali, Bangladesh, and Vietnam from 29 March 2007 (first patient in) to 13 October 2008 (last dose given).

Last subject completed follow-up: 31 March 2009

All data corrections applied (Frozen File): 20 July 2009


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Excluded from the trial before assignment to groups were subjects: with history of active gastrointestinal illness (vomiting, diarrhea, elevated temperature); who were participating in (or expected to participate in) other investigational-product studies; who could not be followed adequately for safety.

Reporting Groups
  Description
RotaTeq™ - Africa Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
Placebo - Africa Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
RotaTeq™ - Asia Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
Placebo - Asia Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Participant Flow:   Overall Study
    RotaTeq™ - Africa     Placebo - Africa     RotaTeq™ - Asia     Placebo - Asia  
STARTED     2733 [1]   2735 [1]   1018 [1]   1018 [1]
Vaccinated at Visit 1     2733     2735     1018     1018  
Vaccinated at Visit 2     2657     2666     1013     1009  
Vaccinated at Visit 3     2613     2612     1009     1007  
COMPLETED     2607 [2]   2601 [2]   1009 [2]   1007 [2]
NOT COMPLETED     126     134     9     11  
Adverse Event                 12                 21                 1                 0  
Lost to Follow-up                 62                 69                 4                 3  
Protocol Violation                 4                 2                 2                 2  
Withdrawal by Subject                 48                 42                 2                 6  
[1] Subjects who passed all entry criteria and who were randomized in to the study
[2] Subjects vaccinated and followed up to 14 days after each dose



  Baseline Characteristics
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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
RotaTeq™ - Africa Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
Placebo - Africa Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
RotaTeq™ - Asia Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
Placebo - Asia Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
Total Total of all reporting groups

Baseline Measures
    RotaTeq™ - Africa     Placebo - Africa     RotaTeq™ - Asia     Placebo - Asia     Total  
Number of Participants  
[units: participants]
  2733     2735     1018     1018     7504  
Age, Customized  
[units: participants]
         
<27 Days     0     1     0     0     1  
27 to 41 Days     536     569     3     7     1115  
42 to 84 Days     2197     2165     1015     1011     6388  
Gender  
[units: participants]
         
Female     1359     1370     464     492     3685  
Male     1374     1365     554     526     3819  
Race/Ethnicity, Customized  
[units: participants]
         
Black     2733     2735     0     0     5468  
Asian     0     0     1017     1016     2033  
Multi-Racial     0     0     1     2     3  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose   [ Time Frame: At least 14 days following the third vaccination ]
  Hide Outcome Measure 1

Measure Type Primary
Measure Title Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose
Measure Description No text entered.
Time Frame At least 14 days following the third vaccination  
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.
Per Protocol Population

Reporting Groups
  Description
RotaTeq™ - Africa Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
Placebo - Africa Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
RotaTeq™ - Asia Three doses of RotaTeq™ (Rotavirus vaccine, live, oral, pentavalent) administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.
Placebo - Asia Three doses of Placebo matching RotaTeq™ administered 28 to 70 days apart, with up to 14 days of safety follow-up after each vaccination and follow-up for acute gastrointestinal episodes (AGEs) until the end of the study.

Measured Values
    RotaTeq™ - Africa     Placebo - Africa     RotaTeq™ - Asia     Placebo - Asia  
Number of Participants Analyzed  
[units: participants]
  2357     2348     991     978  
Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose  
[units: Subjects]
       
Subjects with rotavirus gastroenteritis cases     79     129     38     71  
Subjects without rotavirus gastroenteritis cases     2278     2219     953     907  


Statistical Analysis 1 for Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose
Groups [1] RotaTeq™ - Africa vs. Placebo - Africa
Method [2] Exact binomial test
P Value [3] <0.001
Efficacy = 1-Relative Risk [4] 39.3
95% Confidence Interval ( 19.1 to 54.7 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The number randomized is different from the number analyzed because some data were excluded from the analysis: subjects were classified as unevaluable due to wildtype rotavirus in stool before 14 days Postdose 3, incomplete clinical and/or laboratory results, or stool samples collected out of day range. Rotavirus gastroenteritis cases are subjects with one or more positive episodes. The most severe positive episode is used for the date of the case.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Efficacy>0%. Based on p< 1/(1+k), where p is proportion of subjects with outcome in vaccine group relative to total number of subjects with outcome, and k is ratio of follow-up time; placebo / vaccine. Based on conditional binomial approach.
[4] Other relevant estimation information:
  Efficacy = 1-RR, expressed as a percentage; the RR is the incidence in the vaccine group / the incidence in the placebo group.

Statistical Analysis 2 for Occurrence of Severe Clinical Rotavirus Disease Caused by Any Rotavirus Serotype More Than 14 Days Following the Third Dose
Groups [1] RotaTeq™ - Asia vs. Placebo - Asia
Method [2] Exact binomial test
P Value [3] <0.001
Efficacy = 1-Relative Risk [4] 48.3
95% Confidence Interval ( 22.3 to 66.1 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The number randomized is different from the number analyzed because some data were excluded from the analysis: subjects were classified as unevaluable due to wildtype rotavirus in stool before 14 days Postdose 3, incomplete clinical and/or laboratory results, or stool samples collected out of day range. Rotavirus gastroenteritis cases are subjects with one or more positive episodes. The most severe positive episode is used for the date of the case.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  Efficacy>0%. Based on p< 1/(1+k), where p is proportion of subjects with outcome in vaccine group relative to total number of subjects with outcome, and k is ratio of follow-up time; placebo / vaccine. Based on conditional binomial approach.
[4] Other relevant estimation information:
  Efficacy = 1-RR, expressed as a percentage; the RR is the incidence in the vaccine group / the incidence in the placebo group.



2.  Secondary:   Africa - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8]   [ Time Frame: 14 days following the 3rd vaccination ]

3.  Secondary:   Asia - Serum Anti-rotavirus IgA Responses and Serum Neutralizing Antibody (SNA) Responses Against Rotavirus Serotypes G1, G2, G3, G4, and P1A[8]   [ Time Frame: 14 days following the 3rd vaccination ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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.


  More Information