Comment Period Extended to 3/23/2015 for Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials
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Rotavirus Efficacy and Safety Trial (REST)(V260-006)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00090233
First received: August 25, 2004
Last updated: November 10, 2014
Last verified: November 2014
History of Changes
Results First Received: June 29, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Single Group Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Prevention
Condition: Rotavirus Infections
Interventions: Biological: Rotateq™
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
Participants were recruited at 356 sites in Belgium, Costa Rica, Finland, Germany, Guatemala, Italy, Jamaica, Mexico, Puerto Rico, Sweden, Taiwan, and the United States from 12 Jan 2001 first patient in (FPI) to 06 Oct 2004 last patient in (LPI).

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

Participants with: history of congenital abdominal disorders, intussusception, or abdominal surgery; history of

known prior rotavirus disease, chronic diarrhea, or failure to thrive were excluded from the trial before

assignment to groups.

Reporting Groups
  Description
RotaTeq™ Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart with up to 42 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) through the first rotavirus season postvaccination. The rotavirus season for each site was prospectively determined using historical epidemiologic data.
Placebo Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart with up to 42 days of safety follow-up after each vaccination, and follow-up for acute gastrointestinal episodes (AGEs) through the first rotavirus season postvaccination. The rotavirus season for each site was prospectively determined using historical epidemiologic data.

Participant Flow:   Overall Study
    RotaTeq™     Placebo  
STARTED     34644 [1]   34630 [2]
Vaccinated at Visit 1     34035 [3]   34003 [4]
Vaccinated at Visit 2     31052     31066  
Vaccinated at Visit 3     29667     29598  
COMPLETED     29645 [5]   29565 [5]
NOT COMPLETED     4999     5065  
Randomized Not Vaccinated (Visit 1)                 609                 627  
Adverse Event                 214                 198  
Lost to Follow-up                 68                 95  
Protocol Violation                 960                 1022  
Withdrawal by Subject                 182                 211  
Moved                 203                 189  
Not Specified                 1211                 1160  
Data not available at data cut-off point                 1552                 1563  
[1] Evaluated by data safety monitoring board (DSMB) when they recommended stopping enrollment
[2] Evaluated by data safety monitoring board when they recommended stopping enrollment
[3] Randomized Not vaccinated 609
[4] Randomized Not vaccinated 627
[5] Does not include participants who discontinued prior to the 42 day safety follow-up



  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™ Three oral doses (~6.5x10^7 to ~1.2x10^8 IU/dose) of RotaTeq™ (rotavirus vaccine, live, oral, pentavalent) administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
Placebo Placebo matching RotaTeq™ administered at 3 separate visits scheduled 4 to 10 weeks (28 to 70 days) apart.
Total Total of all reporting groups

Baseline Measures
    RotaTeq™     Placebo     Total  
Number of Participants  
[units: participants]
 		  34644     34630     69274  
Age, Customized [1]
[units: Participants]
 		     
5 Weeks of Age and Under     1     4     5  
6 to 12 Weeks of Age     34551     34527     69078  
Over 12 Weeks of Age     92     99     191  
Gender  
[units: participants]
 		     
Female     17058     17101     34159  
Male     17586     17529     35115  
Race/Ethnicity  
[units: participants]
 		     
White     23772     23788     47560  
Hispanic American     4963     4911     9874  
Black     2908     2941     5849  
Multi Racial     1815     1817     3632  
Asian     536     552     1088  
Native American     531     514     1045  
Other     119     107     226  
[1] The eligibility for this study was to enroll infants 6-12 weeks of age; however infants that were 5 weeks and under, and infants who were 12 weeks and over were inadvertently enrolled outside these ranges. Those infants who received at least 1 dose of study vaccine, were followed for safety.



  Outcome Measures
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1.  Primary:   Intussusception Within 42 Days Following Any Dose of RotaTeq™/Placebo   [ Time Frame: Within 42 days following any dose of RotaTeq™/placebo ]
  Show Outcome Measure 1

2.  Primary:   Occurrence of Rotavirus Disease Caused by Serotypes G1, G2, G3 and G4 That Occurs 14 Days Following the 3rd Vaccination   [ Time Frame: At least 14 days following the 3rd vaccination through the first full rotavirus season ]
  Show Outcome Measure 2

3.  Secondary:   G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus   [ Time Frame: 14 days following the 3rd vaccination ]
  Hide Outcome Measure 3

Measure Type Secondary
Measure Title G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus
Measure Description Number of participants with a 3-fold rise or greater in G1 Serum neutralizing antibody (SNA) responses against rotavirus from baseline to postdose 3.
Time Frame 14 days following the 3rd 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 among participants in Finland using Per-Protocol Case Definition

Reporting Groups
  Description
RotaTeq™ Participants randomized to treatment with RotaTeq™ tested with data available for analysis excluding protocol violators, participants with invalid data based on laboratory determinations, participants with wildtype rotavirus detected in the stool, or with samples taken outside the range of 9 to 33 days postdose 3.
Placebo Participants randomized to treatment with Placebo tested with data available for analysis excluding protocol violators, participants with invalid data based on laboratory determinations, participants with wildtype rotavirus detected in the stool, or with samples taken outside the range of 9 to 33 days postdose 3.

Measured Values
    RotaTeq™     Placebo  
Number of Participants Analyzed  
[units: participants]
 		  117     89  
G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus  
[units: Participants]
 		  95     8  


Statistical Analysis 1 for G1 Serum Neutralizing Antibody (SNA) Responses Against Rotavirus
Groups [1] RotaTeq™
Method [2] Exact binomial test
P Value [3] <0.001
Proportion [4] 81.2
95% Confidence Interval ( 72.9 to 87.8 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  No text entered.
[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:
  p≥42%, where p is proportion of participants with ≥3-fold rise in antibody titer from Predose 1 to Postdose 3 in vaccine group. Based on binomial approach.
[4] Other relevant estimation information:
  No text entered.



4.  Secondary:   Occurrence of Hospital Admissions and Visits to Emergency Departments (or the Equivalent at International Sites) for Rotavirus Disease Associated With Serotypes G1, G2, G3, or G4   [ Time Frame: At least 14 days following the 3rd vaccination ]
  Show Outcome Measure 4

5.  Secondary:   Efficacy of a 3-dose Regimen of RotaTeq™ Against Moderate-to-severe Rotavirus Disease (Clinical Score >8) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose.   [ Time Frame: At least 14 days following the 3rd vaccination through the first rotavirus season ]
  Show Outcome Measure 5

6.  Secondary:   Efficacy of a 3-dose Regimen of RotaTeq™ Against Severe Rotavirus Disease (Clinical Score > 16) Caused by Serotypes G1, G2, G3, and G4 Occurring at Least 14 Days Following the Third Dose   [ Time Frame: At least 14 days following the 3rd vaccination through the first rotavirus season ]
  Show Outcome Measure 6

7.  Secondary:   Seroprotection/Seroconversion for Hepatitis B, Haemophilus Influenzae Type b, Diphtheria, Tetanus, & Polio Types 1,2,& 3 Who Received COMVAX™, INFANRIX™, IPOL™ & PREVNAR™ Concomitantly With RotaTeq™ Versus Placebo   [ Time Frame: 42 days following third dose ]
  Show Outcome Measure 7

8.  Secondary:   Geometric Mean Antibody Titer(s) (GMT) to Pertussis Toxin (PT), Pertussis Filamentous Haemagglutinin (FHA), and Pertussis Pertactin   [ Time Frame: 42 days following third dose ]
  Show Outcome Measure 8

9.  Secondary:   Geometric Mean Antibody Titer(s) (GMT) to Pneumococcal Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F   [ Time Frame: 42 days following third dose ]
  Show Outcome Measure 9


  Serious Adverse Events
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  Other Adverse Events
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  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
70,301 participants randomized, 69,274 evaluated, when DSMB first recommended ending enrollment.


  More Information
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