Fractional Inactivated Poliovirus Vaccine Booster and Rotavirus Study
Condition: Poliomyelitis
MeSH terms: Poliomyelitis
Study type: Interventional
Phase: Phase 4

Summary: 
      This is an open-label phase IV, randomized controlled trial of inactivated poliovirus vaccine
      (IPV) and rotavirus vaccines. This trial will assess immunogenicity of a booster dose of
      fractional IPV (fIPV) in comparison with a full dose of IPV when given after varying IPV and
      fIPV schedules. Differences in immunogenicity of the varying schedules of IPV and fIPV will
      also be examined. Concomitantly, immunogenicity to two different rotavirus vaccines will be
      evaluated.
    

Detailed description: 
      With the switch from trivalent to bivalent oral poliovirus vaccine (OPV) in 2016, the Global
      Polio Eradication Initiative (GPEI) is recommending inactivated poliovirus vaccine (IPV) use
      as one of the potential strategies to respond to outbreaks of type 2 wild type and/or
      circulating vaccine-derived polioviruses. However, the current global inactivated poliovirus
      vaccine (IPV; 0.5 mL, full-dose) supply shortage dramatically limits the number of doses
      available for an effective outbreak response. Therefore, GPEI has proposed use of intradermal
      administration of a booster of fractional IPV (fIPV; 0.1 mL, one-fifth the full-dose) as a
      dose-sparing strategy to increase the number of children vaccinated and stretch IPV supplies.
      No study has compared immunogenicity of a fIPV booster in children previously vaccinated with
      a single IPV. Furthermore, the IPV shortage has led to reconsideration of fIPV use in routine
      immunization programs. Previous studies found that in one and two dose head-to-head
      comparisons, fIPV induced a lower proportion of seroconversion and antibody responses than
      IPV. However, recent studies of seroconversion and priming suggest two fIPV given at least
      eight weeks apart may be more immunogenic than one IPV. Because of these findings and the
      global IPV shortage, the most recent WHO position paper suggests that countries consider
      administering two fIPV at 6 and 14 weeks of age as an alternative to one IPV after the OPV2
      cessation in April 2016. However, no trial has conducted a direct comparison of the
      immunogenicity of IPV at 14 weeks of age with that of fIPV at 6 and 14 weeks of age.

      The immunogenicity of rotavirus (RV) vaccines will also be assessed when given concomitantly
      with IPV/fIPV. Currently, WHO recommends either of two licensed, live attenuated oral
      rotavirus vaccines for all children worldwide: the pentavalent RotaTeq (RV5) and monovalent
      Rotarix (RV1). Many lower income countries where IPV is being introduced are also poised to
      introduce rotavirus vaccine in the coming years. The first dose of OPV interferes with RV
      vaccines and RV vaccines may be more immunogenic when delivered with IPV compared with OPV.
      The proposed study presents an opportunity to compare the two and three dose responses of RV1
      and RV5 when delivered with IPV compared with previous studies in Bangladesh when
      co-administered with OPV.

      In addition, recent studies have suggested that host genetic factors (i.e., Secretor status
      and Lewis and salivary ABO blood group phenotype) mediate susceptibility to rotavirus
      infection. More precisely, non-secretors (i.e., children lacking a functional fucosyl
      transferse-2 [FUT2] gene) have substantially reduced risk of rotavirus infection of certain
      genotypes. Furthermore, certain rotavirus genotypes infected mainly Lewis negative children,
      independent of secretor status. In addition, blood group antigen status has been proposed to
      be associated with infection (or lack of infection) by particular rotavirus genotypes. The
      proposed trial will assess whether Secretor status, Lewis and salivary ABO blood group
      phenotype are also associated with vaccine response.
    

Intervention name(s): IPV at 14 and 22 weeks of age, Rotarix; IPV at 14 and 22 weeks of age, RotaTeq; IPV at 14 and fIPV at 22 weeks, Rotarix; IPV at 14 and fIPV at 22 weeks, RotaTeq; IPV at 6 and fIPV at 22 weeks, Rotarix; IPV at 6 and fIPV at 22 weeks, RotaTeq; fIPV at 6-14-22 weeks of age, Rotarix; fIPV at 6-14-22 weeks of age, RotaTeq
Intervention type(s): Biological; Biological; Biological; Biological; Biological; Biological; Biological; Biological
Intervention description(s): Participants in this arm will receive a full dose of inactivated poliovirus vaccine (IPV) at 14 weeks of age and a full dose IPV booster at 22 weeks of age. They will also receive the rotavirus vaccine, Rotarix, at 6 and 10 weeks of age.; Participants in this arm will receive a full dose of inactivated poliovirus vaccine (IPV) at 14 weeks of age and a full dose IPV booster at 22 weeks of age. They will also receive the rotavirus vaccine, RotaTeq, at 6, 10, and 14 weeks of age.; Participants in this arm will receive a full dose of inactivated poliovirus vaccine (IPV) at 14 weeks of age and a fractional dose IPV (fIPV) booster at 22 weeks of age. They will also receive the rotavirus vaccine, Rotarix, at 6 and 10 weeks of age.; Participants in this arm will receive a full dose of inactivated poliovirus vaccine (IPV) at 14 weeks of age and a fractional dose IPV (fIPV) booster at 22 weeks of age. They will also receive the rotavirus vaccine, RotaTeq, at 6, 10, and 14 weeks of age.; Participants in this arm will receive a full dose of inactivated poliovirus vaccine (IPV) at 6 weeks of age and a fractional dose IPV (fIPV) booster at 22 weeks of age. They will also receive the rotavirus vaccine, Rotarix, at 6 and 10 weeks of age.; Participants in this arm will receive a full dose of inactivated poliovirus vaccine (IPV) at 6 weeks of age and a fractional dose IPV (fIPV) booster at 22 weeks of age. They will also receive the rotavirus vaccine, RotaTeq, at 6, 10, and 14 weeks of age.; Participants in this arm will receive a fractional doses of inactivated poliovirus vaccine (fIPV) at 6 and 14 weeks of age and a fIPV booster at 22 weeks of age. They will also receive the rotavirus vaccine, Rotarix, at 6 and 10 weeks of age.; Participants in this arm will receive a fractional doses of inactivated poliovirus vaccine (fIPV) at 6 and 14 weeks of age and a fIPV booster at 22 weeks of age. They will also receive the rotavirus vaccine, RotaTeq, at 6, 10, and 14 weeks of age.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: inactivated poliovirus vaccine; fractional inactivated poliovirus vaccine; Rotavirus; Rotarix; RotaTeq; fIPV; IPV