Safety and Immunogenicity in Age De-Escalation of PfSPZ Vaccine in Tanzanian Adults, Children, and Infants
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The present trial will evaluate safety and tolerability as well as the vaccine-induced
      humoral and cellular immune responses in healthy Tanzanian adults, adolescents, children, and
      infants who receive doses of 1.8x10^6, 9.0x10^5, 4.5x10^5 or 2.7x10^5 PfSPZ of PfSPZ Vaccine
      by direct venous inoculation (DVI),compared with control groups receiving normal saline (NS)
      placebo by DVI. In addition, as an exploratory objective, controlled human malaria infection
      (CHMI) will be used to assess efficacy in adults three weeks following immunization.
    

Detailed description: 
      This is a single center trial to assess the safety, tolerability and immunogenicity of PfSPZ
      Vaccine administered by direct venous inoculation (DVI) to healthy Tanzanian adults,
      adolescents, and children and infants. 105 healthy male and female; adults, adolescents,
      children and infant volunteers, aged from 6 months to 45 years, who live in the Bagamoyo
      Township will be enrolled based on pre-defined inclusion and exclusion criteria implemented
      according to international ethical standards.

      The safety and tolerability of PfSPZ Vaccine administered as three doses of either 9.0x10^5
      PfSPZ or 1.8x10^6 PfSPZ to healthy Tanzanian adults, adolescents, and children 6 years of age
      or older; and three doses of 4.5x10^5 PfSPZ or 9.0x10^5 PfSPZ to healthy Tanzanian children 1
      to 5 years of age and infants 6 to 11 months of age, in each case compared to NS controls,
      will be evaluated. In addition, as an exploratory objective, controlled human malaria
      infection (CHMI) will be used to assess efficacy in adults three weeks following
      immunization.

      Study Design: This is a single center trial with ten groups (Groups 1a/b: ages 18-45; Group
      2a/b: ages 11-17; Group 3a/b: ages 6-10; Group 4a/b: ages 1-5; and Group 5b/c: ages
      6months-11 months) each with 6 subjects receiving PfSPZ Vaccine and 3 subjects receiving NS
      and an eleventh smaller group (Group 5a: ages 6months-11months) with 3 subjects receiving
      PfSPZ Vaccine; two of these groups (Group 1a/b) contain adult volunteers and will have
      infectivity controls (CHMI 1 and 2) each having 3 subjects, after the vaccination phase of
      the study. The adult volunteers will undergo CHMI 3 weeks after the last immunization.

      For the first immunization, two volunteers (out of six) in Group 1a will receive 9x10^5 of
      PfSPZ Vaccine by DVI as sentinels, to demonstrate safety and tolerability. At the same time,
      one (out of three) corresponding control volunteers will receive NS, in order to maintain
      blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting
      are not met, the remaining four volunteers in Group 1a will also receive a 9x10^5 PfSPZ dose
      of the vaccine and the remaining two placebo recipients will receive NS.

      After review of at least +14 days post vaccination safety data for Group 1a by the SMC, if
      there are no significant safety concerns, two volunteers (out of six) in Group 1b will
      receive 1.8x10^6 PfSPZ, and two volunteers (out of six) in each of the Groups 2a and 3a will
      receive 9x10^5 PfSPZ, of the PfSPZ Vaccine, to demonstrate safety and tolerability, and each
      of these sentinel groups will be joined by one corresponding NS control in order to maintain
      blinding. Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting
      are not met, the remaining four volunteers in Group 1b will receive 1.8x10^6 PfSPZ and the
      remaining four volunteers in each of Groups 2a and 3a will receive 9x10^5 PfSPZ of the PfSPZ
      Vaccine, and the remaining placebo recipients will receive NS.

      After review of at least +14 days post vaccination safety data for Groups 1b, 2a and 3a by
      the SMC, if there are no significant safety concerns, two volunteers (out of six) in each of
      the Groups 2b and 3b will receive 1.8x10^6 PfSPZ, those in Group 4a will receive 4.5x10^5
      PfSPZ and all 3 volunteers in Group 5a will receive 2.7x10^5 PfSPZ of PfSPZ Vaccine, to
      demonstrate safety and tolerability, and each of the sentinel groups (two volunteers from
      Groups 2b, 3b and 4a) will be joined by one NS control in order to maintain blinding.
      Approximately 24 hours later, provided criteria for calling an ad hoc SMC meeting are not
      met, the remaining four volunteers in Groups 2b, 3b and 4a will receive their appropriate
      dose of PfSPZ Vaccine (1.8x10^6 PfSPZ, 1.8x10^6 PfSPZ, and 4.5x10^5 PfSPZ, respectively), and
      the placebo recipients will receive NS.

      Escalation from the small group of infants, (Group 5a, n=3) receiving a single dose of
      2.7x10^5 PfSPZ, to the full group (Group 5b, n=6) receiving three doses of 4.5x10^5 PfSPZ,
      will proceed without SMC review if criteria for calling an ad hoc SMC meeting are not met.
      However, if the criteria are met, an ad hoc SMC meeting will be called to review the data,
      and dose escalation to 4.5x10^5 PfSPZ will be postponed until the recommendations of the SMC
      are available. The interval between the 2.7x10^5 PfSPZ small group and the 4.5x10^5 PfSPZ
      larger group will be a minimum of three days.

      After review of at least +14 days post vaccination, safety data for Groups 2b, 3b, 4a, 5a and
      5b by the SMC, if there are no significant safety concerns, two volunteers (out of six) in
      each of the Groups 4b and 5c will receive 9x10^5 PfSPZ, to demonstrate safety and
      tolerability. At the same time, one (out of three) corresponding control volunteers will
      receive NS, in order to maintain blinding. Approximately 24 hours later, provided criteria
      for calling an ad hoc SMC meeting are not met, the remaining four volunteers in Group 4b and
      5c will receive 9x10^5 PfSPZ dose of the vaccine, and the placebo recipients will receive NS.
    

Intervention name(s): PfSPZ Vaccine; Normal Saline; PfSPZ Challenge (for CHMI)
Intervention type(s): Biological; Other; Biological
Intervention description(s): Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine); 0.9% Sodium chloride; live, infectious, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Challenge) Controlled human malaria infection (CHMI) by direct venous inoculation of 3,200 PfSPZ Challenge
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: PfSPZ Vaccine; Plasmodium falciparum