Pneumococcal Protein Vaccine Safety and Immunogenicity Trial
Condition: Adverse Effects
Study type: Interventional
Phase: Phase 1

Summary: 
      This is an observer-blind, randomised, vaccine-controlled, vaccine trial to determine the
      safety and immunogenicity of a pneumococcal protein vaccine. It will use an age step-down
      approach beginning with adults, then toddlers then infants, with data safety review at each
      stage before stepping down to the next age group. Adults and toddlers will receive the same
      dose of this three-protein (trivalent) vaccine (PcpA, PhtD, and PlyD1 proteins) at 50µg each.
      Infants will then be started at a low dose (10 µg), then medium dose (25µg) then high dose
      (50µg), with safety reviews at each stage before ascending to the next highest dose. Infants
      will also receive concomitant standard EPI childhood vaccines. Safety will be assessed by
      close monitoring beginning on the day of vaccination (day 0) and for the subsequent seven
      days, with recording of solicited and non-solicited adverse events. Immunogenicity will be
      assessed by specific antibody response to the three proteins. The study aims to recruit 280
      study subjects across all age groups.
    

Detailed description: 
      This is a Phase I, single-center, randomized, placebo-controlled, step-down observer-blind
      study to assess the safety and immunogenicity of a single injection PPrV vaccine containing
      50 µg of each protein (PcpA, PhtD and PlyD1) withadjuvant in healthy adults and toddlers, and
      of 3 injections in healthy infants (following the Expanded Program on Immunization [EPI]
      schedule) at 3 ascending dose levels (all adjuvanted 10, 25, and 50µg of each protein per
      dose level; with an additional un-adjuvanted formulation at 25 µg of each protein per dose
      level).

      Overall, there will be 5 Cohorts. In Cohort I, adults will receive 1 injection of adjuvanted
      50 µg PcpA, PhtD and PlyD1 PPrV vaccine (high dose) or placebo.

      In Cohort II, toddlers will receive 1 injection of adjuvanted 50 µg PcpA, PhtD and PlyD1 PPrV
      vaccine or placebo.

      In Cohorts III, IV and V, infants will receive 3 injections of one of the following PPrV
      vaccine formulations: adjuvanted 10 µg each PcpA, PhtD and PlyD1 (low dose), adjuvanted 25 µg
      each PcpA, PhtD and PlyD1 (middle dose), unadjuvanted 25 µg each PcpA, PhtD and PlyD1 (middle
      dose un-adjuvanted), or adjuvanted 50 µg each PcpA, PhtD and PlyD1 (high dose) or placebo,
      according to the EPI schedule (at 6 weeks, 10 weeks and 14 weeks), as well as concomitant
      applicable standard of care childhood vaccines ( Quinvaxem® [DTwP-HepB-Hib] vaccine, Bacillus
      Calmette-Guérin vaccine (BCG) (if not received at birth), and oral poliomyelitis vaccine
      [OPV]).

      As a safety precaution, this trial will use a step-down approach for enrollment: for adults,
      1 vaccination and acceptable review of safety data collected through Day 7 after injection,
      followed by enrollment of toddlers, 1 vaccination and acceptable review of safety data
      collected through Day 7 after injection, and then enrollment of infants (3 injections, EPI
      schedule). For infants, step-wise dose ascension is conditional upon acceptable safety
      reviews, which will be conducted after completion of the third vaccination of the EPI series
      at each dose level, using safety data collected through Day 7 after each of the vaccinations.

      An Independent Data Monitoring Committee (IDMC) will be established for safety oversight of
      this study, for which a formal IDMC charter will be developed. For all safety reviews,
      blinded safety data will be provided to the Sponsor's Safety Management Team (SMT). The
      review will be performed by the SMT with presentation of findings, as per standard early
      safety review process, to the Sponsor's Safety Management Oversight Team (SMOT) in order to
      assess whether proceeding to the next ascending dose level is appropriate. The results will
      be communicated to the IDMC after each review. A formal IDMC review is proposed following
      completion of the Cohort II (toddler) safety review, prior to enrollment of Cohorts III, IV,
      and V (infants).

      The study scheme is summarized in Figure 1, and details of safety reviews are described in
      the periodic safety data review (SDR) section. Electronic data capture (EDC) will be used for
      the collection of data generated in this study.
    

Intervention name(s): Pneumococcal protein vaccine; Pneumococcal protein vaccine; Pneumococcal protein vaccine; Pneumococcal protein vaccine; Pneumococcal protein vaccine
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): One dose of 50 µg of each of three proteins with adjuvant (aluminium hydroxide) IM; Three doses, 4 weeks apart, of 10 µg of each of three proteins with adjuvant (aluminium hydroxide) IM; Three doses, 4 weeks apart, of 25 µg of each of three proteins with adjuvant (aluminium hydroxide) IM; Three doses, 4 weeks apart, of 25 µg of each of three proteins without adjuvant IM; Three doses, 4 weeks apart, of 50 µg of each of three proteins with adjuvant (aluminium hydroxide) IM
Other intervention name(s): pneumococcal common protein vaccine; pneumococcal common protein vaccine; pneumococcal common protein vaccine; pneumococcal common protein vaccine; pneumococcal common protein vaccine
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Safety; immunogenicity; pneumococcal; protein; vaccine