Safety, Tolerability and Immunogenicity of PfSPZ Vaccine in an Age De-escalation Trial in Equatorial Guinea.
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This trial will evaluate the safety, tolerability, and immunogenicity of PfSPZ Vaccine in
      healthy Equatoguinean adults, adolescents, children and infants who receive doses of
      0.9x10^6, 1.8x10^6 or 2.7x10^6 PfSPZ Vaccine via direct venous inoculation (DVI) compared
      with control groups receiving normal saline (NS) placebo by DVI. In addition, the study will
      also assess a second PfSPZ-based vaccination approach known as PfSPZ-CVac- the administration
      of non-irradiated, infectious PfSPZ (PfSPZ Challenge) (1x10^5 PfSPZ) under anti-malarial
      chemoprophylaxis (chloroquine) in younger adults ages 18 to 35 years for safety,
      tolerability, immunogenicity and efficacy against controlled human malaria infection (CHMI).
    

Detailed description: 
      EGSPZV2 is a single center, double-blind, placebo-controlled trial. The study is to take
      place at the Baney Temporary Research Facility (BTRF) located in Baney City. One hundred and
      thirty-five healthy male and female; adults, adolescents, children and infant volunteers,
      aged from 6 months to 65 years who live in the Baney district and Malabo city on Bioko Island
      will be enrolled based on pre-defined inclusion and exclusion criteria implemented according
      to international ethical standards.

      The trial will consist of seven groups (Group 1a: younger adults, ages 18-35; Group 2: older
      adults, ages 36-65; Group 3: adolescents, ages 11-17; Group 4: older children, ages 6-10;
      Group 5: younger children, ages 1-5; Groups 6a/b: infants, ages 6 months - 11 months) of
      volunteers. Vaccination will begin in Group 1a (younger adults), with three doses of 2.7x10^6
      PfSPZ Vaccine given eight weeks apart by DVI. An eighth group (Group 1b: younger adults, ages
      18- 35), will be uniquely immunized with the comparator vaccine PfSPZ Challenge given under
      chloroquine prophylaxis (PfSPZ-CVac approach), rather than with PfSPZ Vaccine. A single
      PfSPZ-CVac younger adult group (group 1b) is included to provide a direct comparison with
      PfSPZ Vaccine (group 1a) for the ability to protect against CHMI. Each of the first two
      groups (1a and 1b) will have 20 participants receiving either PfSPZ Vaccine or PfSPZ
      Challenge and 6 participants receiving NS placebo by DVI, with treatment allocation
      randomized and double-blind. Volunteers in Group 1b will receive vaccinations 8 weeks after
      the initial vaccination of Group 1a. Volunteers in Group 1 (younger adults) will receive CHMI
      between 10 and 14 weeks post last vaccination (with a window of +/- 7 days on each side) and
      will be followed for 8 weeks following CHMI.

      Group 2 (older adults) will receive three doses of 2.7x10^6 PfSPZ Vaccine. Group 2 will
      consist of 12 participants receiving PfSPZ Vaccine and 4 participants receiving NS placebo by
      DVI, given eight weeks apart. Group 3, 4, 5 and 6b will each have 12 participants receiving
      three doses of 1.8x10^6 PfSPZ Vaccine and 4 participants receiving NS, also given eight weeks
      apart. Group 6a will consist of 3 volunteers who will receive a single dose of 9.0 x10^5
      PfSPZ Vaccine.

      Sequential age groups will be staggered to allow assessment of safety and tolerability before
      further age de-escalation. To assure safety, vaccinations will start in younger adults and
      will progress to younger and older age groups using staggered start dates at approximately
      weekly intervals. Age escalation and initial age de-escalation will take place at the same
      time, hence Group 2 and 3 will be vaccinated at the same time. Progressively younger age
      groups will then be immunized. The decision to proceed with each of these steps will be made
      by the study team after a review of safety data from the previously vaccinated group(s).
      Three Safety Monitoring Committee (SMC) meetings are scheduled to review data prior to
      initiating the younger children and infant groups.
    

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