Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules

Overview

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.

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 significant increase in fever, diarrhea, vomiting, or intussusception in the mixed schedule groups when compared with the recommended schedule of the single vaccine alone group. Normal healthy full-term infants who are scheduled to receive their routine infant immunizations and who are at least 6 weeks of age and no more than 14 weeks, 6 days of age at Visit 1 will be recruited from their primary care clinic. Infants will be randomized (open label) to one of 5 different rotavirus vaccine study groups. Two study groups will be administered the standard RotaTeq® or Rotarix® vaccines as 3 and 2 doses, respectively, and 3 study groups will be administered mixed sequences of RotaTeq® and Rotarix® given as 3 doses. All rotavirus vaccines will be administered concurrently with the other routinely administered childhood vaccines. Parents/legal guardians will be given a memory aid and a thermometer, and asked to record any suspected fever (with measured temperature documented) or adverse events for Days 1-8 after vaccination. At approximately 1 week after vaccination, study personnel will contact the parents/legal guardians, review the completed memory aid, and record the findings on the case report form. Blood for immunogenicity testing will be obtained 3-6 weeks after the last dose of vaccine. For the four 3-dose rotavirus vaccine study groups, blood will be obtained at approximately 7 months of age (3-6 weeks after the last rotavirus vaccine dose). For the single Rotarix® vaccine study group, blood will be obtained at approximately 5 months of age (3-6 weeks after the last dose of Rotarix® vaccine). The primary analysis will be based on rates of induction of anti-rotavirus serum immunoglobulin (Ig) A in the 5 study groups 3-6 weeks