Safety and Immunogenicity of Sequential Rotavirus Vaccine Schedules
Condition: Rotavirus Infection
MeSH terms: Rotavirus Infections
Study type: Interventional
Phase: Phase 4

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 description: 
      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
    

Intervention name(s): Rotarix®; RotaTeq®
Intervention type(s): Biological; Biological
Intervention description(s): Each 1-mL dose of Rotarix® contains a suspension of at least 10^6 median Cell Culture Infective Dose (CCID50) of live, attenuated human G1P rotavirus after reconstitution. The lyophilized vaccine contains amino acids, dextran, Dulbecco's Modified Eagle Medium (DMEM), sorbitol, and sucrose. The liquid diluent contains calcium carbonate, sterile water, and xanthan. The diluent includes an antacid component (calcium carbonate) to protect the vaccine during passage through the acid environment of the stomach. Rotarix® contains no preservatives. Once reconstituted, the vaccine will appear white and turbid.; 2-mL ready-to-use oral solution of live reassortant rotaviruses, containing G1, G2, G3, G4, and P1A, which contains a minimum of 2.0 to 2.8 x 10^6 infectious units (IU) per individual reassortant dose, depending on the serotype, and not greater than 116 x 10^6 IU per aggregate dose. The buffered stabilizer solution contains sucrose, sodium citrate, sodium phosphate monobasic monohydrate, sodium hydroxide, polysorbate 80, cell culture media, and trace amounts of fetal bovine serum. RotaTeq® contains no preservatives. RotaTeq® is a pale yellow clear liquid that may have a pink tint.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: vaccine, rotavirus, gastroenteritis, infants