Efficacy, Safety and Immunogenicity Study of GlaxoSmithKline(GSK) Biologicals' Candidate Malaria Vaccine 257049 in the Sporozoite Challenge Model in Healthy Malaria-naïve Adults
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 2

Summary: 
      This study is designed to evaluate safety, reactogenicity, immunogenicity, and efficacy of
      GSK Biological's malaria candidate vaccine 257049 administered as standard doses at 0 and 1
      months and 1/5th standard dose at 7 months (delayed fractional dose group) and 257049
      administered as three standard doses one month apart (0, 1, 2-month group) in healthy
      malaria-naïve volunteers aged 18-50 years in the sporozoite challenge model.

      An additional, delayed sporozoite challenge will assess persistence of protection induced by
      the primary immune schedule and if an additional dose can provide protection in those
      unprotected by the initial vaccination series.
    

Detailed description: 
      This protocol posting has been amended to reflect changes in Amendment 1 of the Protocol (20
      April 2014).

      Rationale for Protocol Amendment 1:

      • In order to assess whether protection is maintained over time, and assess boostability, the
      protocol has been amended to incorporate another sporozoite challenge, after a single boost
      of 1/5th standard dose of RTS,S/AS01B, or no boost.

      Study design:

        -  Dependent upon enrolment date during the screening period, the study duration will be
           approximately 19 months for each vaccinated subject in the delayed fractional dose
           group, 14 months for each vaccinated subject in the 0, 1, 2-month group, 7 months for
           each infectivity control subject in the challenge phase and 6 months for each
           infectivity control subject in the rechallenge phase.

        -  Vaccination schedules:

             -  0, 1, 7-month followed by sporozoite challenge 21 days (3 weeks) after the third
                vaccination, with subsequent boosting/no boosting at Booster Phase Study Day 0
                followed by sporozoite rechallenge 3 weeks post boost/no boost.

             -  0, 1, 2-month followed by sporozoite challenge 21 days (3 weeks) after the third
                vaccination, with subsequent boosting/no boosting at Booster Phase Study Day 0
                followed by sporozoite rechallenge 3 weeks post boost/no boost.

        -  Safety and immunogenicity will be evaluated during the study up to 3 months after
           rechallenge (Booster Phase Study Day 105).

        -  Treatment allocation:

             -  Non-randomized for primary phase; subjects will be enrolled to different study
                groups in a consecutive manner, to ensure the day of sporozoite challenge
                (conducted over two days) is the same for all.

             -  For the booster and rechallenge phase, subjects unprotected during the first
                challenge will receive a 1/5th RTS,S/AS01B booster dose while subjects from each
                group who were protected in the first challenge will be randomized to receive a
                1/5th RTS,S/AS01B booster dose or no booster dose.

      This protocol posting has been amended to reflect changes in Amendment 2 of the Protocol (08
      January 2015) Rationale for Protocol Amendment 2: In order to have sufficient blood samples
      for future assay development or testing, evaluation of Hepatitis B (HBs) cellular-mediated
      immunogenicity (CMI) was de-prioritised from a secondary outcome measure to a tertiary
      secondary outcome measure and will only be conducted if sufficient cells are available from
      the thawn cryotube(s) that will be used for circumsporozoite protein (CS) testing.
    

Intervention name(s): GSK257049 Dosage 1; GSK257049 Dosage 2; Sporozoite-infected mosquitoes challenge
Intervention type(s): Biological; Biological; Procedure
Intervention description(s): RTS,S/AS01B administered as 0.5 mL dose at 0 and 1 months and 0.1 mL dose at 7 months for 0,1,7 M Group (delayed fractional dose group). In subjects unprotected in the first challenge, to receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge. In subjects protected in the first challenge, randomization to receive or not receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge.; RTS,S/AS01B administered as three doses of 0.5mL given one month apart (0, 1, 2 M group) in the challenge model. In subjects unprotected in the first challenge, to receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge. In subjects protected in the first challenge, randomization to receive or not receive a booster with a fractional dose of RTS,S/AS01B followed by rechallenge.; Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the volunteers. For each volunteer, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored.
The challenge is scheduled to occur approximately 21 days (3 weeks) after the last vaccination visit (Study Day 196). Volunteers who reconsent for the boost/rechallenge phase will be rechallenged with sporozoite-infected mosquitoes, scheduled to occur approximately 21 days (3 weeks) after the booster dose (Booster Phase Study Day 21).
Other intervention name(s): S/AS01B; RTS; RTS; S/AS01B
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Efficacy; Sporozoite challenge model; Malaria; Immunogenicity; Malaria- naïve adults; Safety