Immune Equivalence Between Multi-dose and Single Dose Formulation of Vi-DT and Their Overall Safety (Phase III)
Condition: Typhoid
MeSH terms: Typhoid Fever
Study type: Interventional
Phase: Phase 3

Summary: 
      This is a multicenter, randomized, observer-blinded, controlled, immune equivalence study of
      a multi-dose (MD) formulation with 2PE preservative of SK bioscience Vi-DT compared to single
      dose (SD) formulation without preservative of SK bioscience Vi-DT in participant (6 months -
      45 years) including safety population.

      The study objectives are as follows:

        -  Primary objective. Demonstrate the immune equivalence as measured by anti-Vi IgG
           Geometric Mean Titer (GMT) of multi dose formulation against single dose formulation of
           Vi-DT (18-45 year age stratum), at 4 weeks after a single dose.

        -  Secondary objective 1. Demonstrate the immune equivalence as measured by seroconversion
           rates of anti-Vi IgG antibody titres of multi dose formulation against single dose
           formulation of Vi-DT vaccine (18-45 year age stratum) at 4 weeks after a single dose.

        -  Secondary objective 2. Describe safety profile in all age strata combined (age 6 months
           - 45 years old) and in each age stratum, at 4 weeks after a single dose of SD/MD
           formulation/control (Meningococcal Conjugate Vaccine).

      There are total 5 scheduled visits as follows:

        -  Visit 1(D-7 to 0): Screening

        -  Visit 2(D0): Enrollment, vaccination, safety follow-up and blood collection for
           immunogenicity assessment (only for subjects 18 years old and above)

        -  Visit 3(D7): Safety follow-up

        -  Visit 4(D28): Safety follow-up and blood collection for immunogenicity assessment (only
           for subjects 18 years old and above)

        -  V5(D168): Safety follow-up
    

Detailed description: 
      The vaccines will be administered to 1,500 healthy participants of 6 months to 45 years of
      age and followed up for 24 weeks after the injection for safety. Adult participants (N=500)
      will be followed up for immunogenicity at 4 weeks and all participants till 24 weeks for
      safety post single dose of either MD & SD formulations. 300 healthy participants will be
      given control vaccine (locally available licensed Meningococcal conjugate vaccine) to check
      the background safety events. The primary objective is to demonstrate the equivalence of
      immunogenicity as measured by anti-Vi IgG GMT titer at 4 weeks after a single dose of MD/SD
      formulation in adults. The secondary objective is to demonstrate the equivalence of
      immunogenicity in terms of seroconversion rates as measured by anti-Vi IgG ELISA antibody
      titers, at 4 weeks after a single dose of MD/SD formulation in adults. A descriptive
      evaluation of safety at 4 and 24 weeks post single dose of (SD/MD/Meningococcal vaccine),
      will be performed. The Vi-DT vaccine from both MD & SD formulations will be administered as a
      single dose of 25 µg/0.5 mL.

      Eligible participants enrolled into the study will be randomized into one of the three study
      groups within each age stratum of 6 months to less than 2 years, 2 to less than 18 years, and
      18 to 45 years. Participants will be observed at the study site for 30 minutes after
      vaccination for safety assessment. Solicited adverse events will be recorded on a diary card
      during 7 days after vaccination. Unsolicited adverse events will be recorded during the 4
      weeks after vaccination. Serious adverse events will be recorded during the entire study
      period. With the exception of designated study site personnel responsible for vaccine
      administration, site investigators, study nurse, and those assessing clinical outcomes, and
      data analysts will be blinded to vaccine allocation until data base lock for the final
      analysis.

      Blood samples will be collected at baseline prior to vaccination and at 4 weeks post
      vaccination from adults (18-45 years) for immunogenicity assessment
    

Intervention name(s): Vi-DT (Multi-dose formulation); Vi-DT (Single dose formulation); Control Vaccine
Intervention type(s): Biological; Biological; Biological
Intervention description(s): Manufacturer: SK bioscience Co., Ltd.
Dose formulation: 25 µg Vi polysaccharide /0.5 mL, presented in Type I glass vial (multi dose Vi-DT with preservative 2 PE)
Mode of Administration: 0.5 mL by intramuscular injection in the left anterolateral thigh or left arm deltoid region in participants below 2 years of age, less dominant arm deltoid region in age group 2 to 45 years
Storage Conditions: +2 to +8°C; Manufacturer: SK bioscience Co., Ltd.
Dose formulation: 25 µg Vi polysaccharide /0.5 mL, presented in Type I glass vial (single dose Vi-DT without any preservative)
Mode of Administration: 0.5 mL by intramuscular injection in the left anterolateral thigh or left arm deltoid region in participants below 2 years of age, less dominant arm deltoid region in age group 2-45 years
Storage Conditions: +2 to +8°C; For participant ≥ 1 year one dose of locally licensed Meningococcal conjugate vaccine will be administered
For participants 6 months to 1 year one dose of locally licensed Meningococcal conjugate vaccine will be administered during the study and the next dose will be provided after the study unblinding at the completion of 6 months follow up of last subject.
Other intervention name(s): Vi polysaccharide typhoid vaccine conjugated with Diphtheria toxoid protein; Vi polysaccharide typhoid vaccine conjugated with Diphtheria toxoid protein; Locally available Meningococcal conjugate vaccine
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants age 6 months to 45 years
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Typhoid conjugate vaccine; Vi-DT; Safety; Immunogenicity