Poliovirus Vaccine Trial in Bangladesh
Condition: Healthy Infants
Study type: Interventional
Phase: Phase 4

Summary: 
      This randomized clinical trial will assess the immune response in infants following
      administration of three types of oral poliovirus vaccine trivalent OPV (tOPV), monovalent OPV
      type 1 (mOPV1), bivalent OPV types 1 and 3 (bOPV) using two different schedules: a short
      schedule with administration at two week intervals and the usual schedule at four week
      intervals. The results of this study will guide the Global Polio Eradication Program in the
      implementation of new strategies that may: 1) improve the quality of the response to
      outbreaks following importation of wild poliovirus type 1 by shortening the interval at which
      several OPV doses are provided; 2) prevent alternate outbreaks of type 1 and type 3
      poliovirus by using bOPV in outbreak responses in countries with weak routine immunization
      systems; and 3) prevent the emergence of type 2 vaccine-derived poliovirus through the
      replacement of tOPV with bOPV in immunization campaigns and routine immunization programs.
    

Detailed description: 
      This is a phase IV, randomized controlled clinical trial of three types of oral poliovirus
      vaccines provided at 2-week or 4-week intervals.

      The study will enroll 1,000 participants from rural Matlab and urban Dhaka.

      In this study infants will be given two different types of oral poliovirus vaccine,
      monovalent OPV type 1 (mOPV1) and bivalent OPV types 1 and 3 (bOPV) using two different
      schedules: a short schedule with administration at two week intervals and the usual schedule
      at four week intervals. The immune responses to these vaccines and schedules will be compared
      with the response to the routine oral polio vaccine schedule in Bangladesh of trivalent oral
      polio vaccine (tOPV) given at 4 week intervals.

      The study will use a randomized controlled trial design. Eligible infants will be randomized
      at 6 weeks of age to one of five study arms: A) 3 doses of bOPV at 6, 8 and 10 weeks of age
      (2-week interval between doses); B) 3 doses of bOPV at 6, 10 and 14 weeks of age (4-week
      interval between doses); C) 3 doses of mOPV1 at 6, 8 and 10 weeks of age (2-week interval
      between doses); D) 3 doses of mOPV1 at 6, 10 and 14 weeks of age (4-week interval between
      doses); and E) 3 doses of tOPV at 6, 10 and 14 weeks of age (4-week interval between doses).
      Currently, tOPV is provided in routine immunization in Bangladesh at the same age as proposed
      in this study. bOPV, mOPV1 and mOPV3 are licensed in several countries and the World Health
      Organization (WHO) has recommended its use in immunization campaigns among children 0 to 5
      years in response to circulation of type 1 and type 3 wild poliovirus, and to prevent
      outbreaks in countries at risk.

      To assess the immunogenicity of each study vaccine and vaccination schedule, antibody titers
      against poliovirus types 1, 2 and 3 will be determined in sera extracted from blood collected
      before (at 6 weeks of age) and after receiving 3 doses of study vaccine. Seroconversion will
      be defined as a titer 4-fold higher than the expected fall in maternally derived antibodies,
      assuming a half life of 28 days. The initial antibody titer at 6 weeks of age will be used as
      the starting point for the expected decline in maternal antibody. We will calculate a
      one-sided 95% confidence interval for the difference between the proportion of
      seroconversions achieved in the short interval study arms and the longer interval study arms.
      If the confidence interval does not include 10%, we will conclude that the short interval is
      not inferior to the longer interval. This same analysis will be applied to the difference
      between bOPV and mOPV1.

      This study will answer the following questions:

        1. Is the immunogenicity of 3 doses of bOPV non inferior to that of 3 doses of mOPV1
           against type 1 poliovirus?

        2. Is an interval of 2 weeks between bOPV or mOPV1 doses non inferior to an interval of 4
           weeks?

        3. Will replacement of tOPV with bOPV in the routine immunization schedule achieve similar
           or higher proportions of children immune to type 1 and 3 polioviruses? The answers to
           these questions will guide the Global Polio Eradication Program in implementing new
           strategies that may: 1) improve the quality of the response to outbreaks following
           importation of wild poliovirus type 1 by shortening the interval at which several OPV
           doses are provided; and 2) prevent alternate outbreaks of type 1 and type 3 poliovirus
           by using bOPV instead of monovalent OPVs; and 3) prevent the emergence of type 2
           vaccine-derived poliovirus through the replacement of tOPV with bOPVin immunization
           campaigns and in routine immunization programs.
    

Intervention name(s): Bivalent OPV 2 week interval; Bivalent OPV 4 week interval; Monovalent OPV 2 week interval; Monovalent OPV 4 week interval; Trivalent OPV 4 week interval
Intervention type(s): Biological; Biological; Biological; Biological; Biological
Intervention description(s): Group A will receive 3 doses of bOPV at 6, 8 and 10 weeks of age (2-week interval between doses).; Group B will receive 3 doses of bOPV at 6, 10 and 14 weeks of age (4-week interval between doses).; Group C will receive 3 doses of mOPV1 at 6, 8 and 10 weeks of age (2-week interval between doses).; Group D will receive 3 doses of mOPV1 at 6, 10 and 14 weeks of age (4-week interval between doses).; Group E will receive 3 doses of tOPV at 6, 10 and 14 weeks of age (4-week interval between doses and similar to the current routine immunization schedule).
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: poliovirus,; trivalent oral polio vaccine,; bivalent oral polio vaccine,; monovalent oral polio vaccine