Safety, Tolerability and Efficacy of PfSPZ Vaccine in Healthy Children and Infants 5 Months - 9 Years Living in Kenya
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This study will be conducted in Siaya County in Nyanza Province, western Kenya. Healthy
      children aged 5 months through 9 years of age living within approximately 10 km of the study
      clinic(s) (Siaya County Referral Hospital, or Wagai dispensary, a government health facility
      in Wagai division) will be eligible for participation in Part 1; healthy infants aged 5
      months - 12 months inclusive will be eligible for Part 2.
    

Detailed description: 
      Part 1: Age De-Escalation and Dose Escalation Part 1 of this trial is a randomized blinded
      evaluation of the safety and tolerability of PfSPZ Vaccine administered by DVI in healthy
      children and infants living in an area of high malaria transmission. A maximum of 156
      children from 5 months to 9 years inclusive at vaccination will be enrolled and randomized to
      receive vaccine or normal saline (NS) placebo by DVI. Total participation time in the dose
      escalation trial ranges from 5-16 weeks per participant from screening visit to close out or
      4 - 12 weeks from enrolment to close out.

      Vaccination will begin in the 5-9 year age group at a dosage of 4.5 x10^5 PfSPZ. A single
      vaccination will be administered by DVI to each of 12 participants aged 5-9 years (inclusive)
      of age, 8 receiving PfSPZ vaccine and 4 participants receiving NS placebo by DVI, with
      treatment allocation randomized and double-blind. Once the initial dose has been shown to be
      well tolerated and without safety concerns, the next higher dose of 9.0 x 10^5 PfSPZ will be
      administered to a second group of 5-9 year olds. Once this has been shown to be well
      tolerated and without safety concerns, the highest dose of 1.8 x 10^6 PfSPZ will be given to
      a third group of 5-9 year olds and concurrently the lowest dose (1.35 x10^5) will be given to
      a same-sized group of younger children aged 13-59 months. Two weeks later, this dose will be
      escalated to 2.7 x10^5 PfSPZ in a second group of children aged 13-59 months. Only once this
      dose is shown to be well-tolerated and without safety concerns will PfSPZ Vaccine, at the
      lowest dose, be given to infants aged 5 - 12 months. Within each age group, dosages will
      increase stepwise until they reach 1.8 x 10^6 PfSPZ, with the initiation of each group
      staggered by at least 2 weeks, provided that no safety thresholds are surpassed. In each
      dosage level, the PfSPZ Vaccine or placebo will be provided to a limited number of
      participants each day (e.g. 3 participants from one age group on days 1 through 4). The PfSPZ
      Vaccine dose will only be increased to the next dose level when safety has been assessed in
      subjects of the first group. The same procedures will be followed for all doses. Children in
      all age groups who are enrolled to receive the 2 highest doses, i.e. 9.0 x 10^5 or 1.8 x 10^6
      PfSPZ, or placebo, will receive a second vaccination of the same dose after 8 weeks, provided
      the first vaccination at this dose level did not show safety signals.

      Part 2: Safety and Efficacy Part of this study will be conducted in the outpatient areas of
      Siaya County Referral Hospital, a large referral hospital in western Kenya and in Wagai
      dispensary. A maximum of 416 infants from 5 M to 12 M inclusive at vaccination will be
      enrolled into this safety and efficacy trial and randomized to receive PfSPZ Vaccine at a
      dose determined during Part 1 of the trial (dose escalation), but likely to be 4.5x10^5, 9.0
      x10^5and 1.8 x 10^6 administered x 3 doses ; and NS placebo administered x 3 doses, all by
      DVI administered at 8 week intervals.

      Participants (N = 416, with 104 in each study arm) will be randomly assigned in a double
      blinded fashion to receive one of the following PfSPZ Vaccine regimes:

      Group 1 (N=104): The highest dose that is determined to be safe and well tolerated in the
      Part 1 trial, administered in 3 doses by DVI at 0, 8 and 16 weeks. Likely dosage will be 1.8
      x 10^6 PfSPZ per dose.

      Group 2 (N=104): The second highest dose, which is half of the highest dose, administered in
      3 doses by DVI at 0, 8 and 16 weeks. Likely dosage will be 9.0 x 10^5 PfSPZ per dose.

      Group 3 (N=104): A lower dose (half of the second highest dose) administered in 3 doses by
      DVI at 0, 8, 16 weeks. Likely dosage will be 4.5x 10^5 PfSPZ per dose.

      Group 4 (N=104): A placebo arm, will receive NS by DVI, 3 times at 8 week intervals.
    

Intervention name(s): PfSPZ Vaccine; Normal Saline
Intervention type(s): Biological; Other
Intervention description(s): Aseptic, purified, cryopreserved, radiation-attenuated Plasmodium falciparum sporozoites; 0.9% Sodium chloride
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Plasmodium falciparum; PfSPZ Vaccine