Clinical Trial: Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules With RotaTeq® and Rotarix®

Brief Summary: Rotavirus, sometimes called the "stomach flu," is the most common cause of severe diarrhea in children. Vaccines can prevent many types of infections and work by causing the body to make proteins called antibodies that fight infection. For some vaccines, more than one vaccination is needed so that the body will make enough antibodies to fight infection. The vaccines (RotaTeq® or Rotarix® oral vaccines) given in this study are recommended for infants by the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP). These vaccines require either 2 or 3 vaccinations to be effective. Healthy infants between 6 weeks and 14 weeks, 6 days of age at Visit 1 will participate for about 10-12 months. Study procedures include reaction assessment and blood sample.

Detailed Summary: Rotavirus is the most common cause of severe gastroenteritis among children. The purpose of the proposed study is to determine the non-inferiority and safety of the 2 licensed rotavirus vaccines when both are administered to the same child during sequential vaccinations. Both Rotarix® and RotaTeq® vaccines have been evaluated for safety and efficacy in placebo-controlled trials with more than 70,000 infants each and it is likely that both vaccines delivered in various combinations will be safe and effective. Since RotaTeq® was licensed in the United States (US) in 2006, approximately 6 million doses have been administered in the US. In addition, Rotarix® has been licensed in over 100 nations worldwide and has been delivered to many children in Latin America where it has been recommended for universal vaccination for over 2 years. Now both RotaTeq® and Rotarix® are licensed in the US, and it is expected that health care providers will administer both vaccines. A 3-dose regimen is recommended for RotaTeq® and a 2-dose regimen for Rotarix®. From previous experience, it is likely that one of the vaccines may become unavailable for some period or pediatric offices may switch from one vaccine to the other. Thus, it is probable that mixed schedules will be administered to infants. The primary objective is to determine if the proportion of seroresponders in the sequential mixed rotavirus vaccine groups (RotaTeq® and Rotarix®) is non-inferior to the proportion of seroresponders in the recommended schedule of the single vaccine alone group. Secondary Objectives are: to determine the neutralizing rotavirus antibody responses to the most common rotavirus serotypes (G1-G4 and G9) at 3-6 weeks after the last vaccination for both the sequential, mixed rotavirus vaccine schedule and the single rotavirus vaccine recommended schedule; and to determine if sequential mixed rotavirus vaccine schedules are safe with no statistically signi
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

• Number of Participants Developing a Serum Anti-rotavirus Immunoglobulin (Ig) A Titer of 20 or Greater in the WC3 IgA Assay [ Time Frame: 3-6 weeks after the last vaccination ]
  Blood was collected from all participants at the follow up visit 3-6 weeks after the last vaccination for testing in the ELISA assay to determine the anti-rotavirus IgA antibody titer. A participant met the threshold of a positive response if the post vaccination anti-rotavirus IgA antibody titer was 20 or greater.
• Number of Participants Developing a Serum Anti-rotavirus Immunoglobulin (Ig) A Titer of 20 or Greater in the 89-12 IgA Assay [ Time Frame: 3-6 weeks after the last vaccination ]
  Blood was collected from all participants at the follow up visit 3-6 weeks after the last vaccination for testing in the ELISA 89-12 assay to determine the anti-rotavirus IgA antibody titer. A participant met the threshold of a positive response if the post vaccination anti-rotavirus IgA antibody titier was 20 or greater.
• Geometric Mean Serum Anti-rotavirus IgA Titer [ Time Frame: 3-6 weeks after the last dose of vaccine ]
  Blood was collected from all participants at the follow up visit 3-6 weeks after the last vaccination for testing in the ELISA assay to determine the anti-rotavirus IgA antibody titers. The geometric mean titers (GMT) for each group were calculated along with the 95% confidence intervals.

Original Primary Outcome:

• Geometric mean titer (GMT) serum anti-rotavirus immunoglobulin (Ig)A. [ Time Frame: 1 month after the last dose of vaccine. ]
• Seroresponse rate [proportion of subjects developing serum anti-rotavirus immunoglobulin (Ig) A >/=20 units]. [ Time Frame: 1 month after the last dose of vaccine. ]

Current Secondary Outcome:

• GMT of Neutralizing Rotavirus Antibody to the Most Common Rotavirus Serotypes (G1-G4 and G9) [ Time Frame: 3-6 weeks after the last dose of vaccine. ]
  Blood was collected from all participants at the follow up visit 3-6 weeks after the last vaccination for testing in the neutralizing antibody assay against the most common rotavirus serotypes, G1-G4 and G9. Antigen-specific geometric mean titers (GMT) for each group were calculated along with the 95% confidence intervals.
• Number of Participants Experiencing Solicited Systemic Reactions in the 8 Days After Vaccination [ Time Frame: Days 1-8 after each vaccination ]
  The participants' parent/guardian was given a memory aid to record for 8 days the presence of solicited reactions of fever, diarrhea and vomiting. Fever was considered experienced if the participant was assessed with an axillary temperature of 100.4F or greater on any day in the 8-day period after any vaccination. Diarrhea was considered experienced if the participant had 3 or more looser than normal stools in a day. Vomiting was considered experienced if the participant vomited 2 or more times in a day.
• Number of Participants Experiencing Hematochezia at Any Time During the Study [ Time Frame: Day 1 through 6 months after the last vaccination ]
  Hematochezia was defined as any stools that are black and tarry; maroon in color; or frank red blood. At each visit, signs of hematochezia were assessed and the participant's parent/guardian was instructed to contact the clinical site at any time if the participant had evidence of hematochezia.
• Number of Participants Developing Neutralizing Rotavirus Antibody to Rotavirus Serotypes G1, G2, G4P6 and G9 [ Time Frame: 3-6 weeks after the last dose of vaccine. ]
  Blood was collected from all participants at the follow up visit 3-6 weeks after the last vaccination for testing in the ELISA assay to determine the antibody titers to rotavirus serotypes G1, G2, G4P6 and G9. A participant met the threshold of a positive response if the post vaccination antigen-specific antibody titer was 10 or greater.
• Number of Participants Developing Neutralizing Rotavirus Antibody to Rotavirus Serotype G3 [ Time Frame: 3-6 weeks after the last dose of vaccine. ]
  Blood was collected from all participants prior to vaccination and at the follow up visit 3-6 weeks after the last vaccination for testing in the ELISA assay to determine the antibody titers to rotavirus serotype G3. A participant met the threshold of a positive response if the post vaccination antibody titer was 10 or greater.
• Number of Participants Developing Neutralizing Rotavirus Antibody to Rotavirus Serotypes G4P8 [ Time Frame: 3-6 weeks after the last dose of vaccine. ]
  Blood was collected from all participants at the follow up visit 3-6 weeks after the last vaccination for testing in the ELISA assay to determine the antibody titers to rotavirus serotype G4P8. A participant met the threshold of a positive response if the post vaccination antibody titer was 10 or greater.

Original Secondary Outcome:

• Seroresponse rate [proportion of subjects developing neutralizing rotavirus antibody to the most common rotavirus serotypes (G1-G4 and G9)]. [ Time Frame: 1 month after the last dose of vaccine. ]
• Comparison of systemic reaction incidences. [ Time Frame: After either the mixed vaccine or the single vaccine schedules. ]
• GMT of neutralizing rotavirus antibody to the most common rotavirus serotypes (G1-G4 and G9). [ Time Frame: 1 month after the last dose of vaccine. ]

Dates:
Date Received: December 23, 2010
Date Started: March 2011
Date Completion:
Last Updated: October 23, 2014
Last Verified: September 2014