Sanaria™ PfSPZ Challenge Vaccine
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will randomize 30 healthy adult participants to one of three cohorts comprised of
      six groups of 5 individuals per group to simultaneously receive PfSPZ Challenge via the ID
      route. The goal will be to determine the optimal dose required to achieve 100% infectivity
      (ID100) of adult volunteers with P. falciparum malaria.
    

Detailed description: 
      Study Phase and Design Phase I with experimental malaria challenge. The study will enroll 30
      healthy adult participants randomized to one of three cohorts comprised of six groups of 5
      individuals per group to simultaneously receive PfSPZ Challenge via the ID route. The goal
      will be to determine the optimal dose required to achieve 100% infectivity (ID100) of adult
      volunteers. The parameters of 1) dose (number of sporozoites) 2) number of injections and 3)
      aliquot volume will be studied; adding to previous data collected at the University of
      Nijmegen. The following single time point inoculation regimens (a-f) will be assessed: Cohort
      1: Medium dose, medium aliquot volume: a. 10,000 PfSPZ ID in 2 divided doses of 50 microliter
      aliquot volume b. 10,000 PfSPZ ID in 8 divided doses of 50 microliter aliquot volume Cohort
      2: Medium dose, low aliquot volume: c. 10,000 PfSPZ ID in 2 divided doses of 10 microliter
      aliquot volume d. 10,000 PfSPZ ID in 8 divided doses of 10 ml aliquot volume Cohort 3: High
      dose, low aliquot volume: e. 50,000 PfSPZ ID in 2 divided doses of 10 ml aliquot volume f.
      50,000 PfSPZ ID in 8 divided doses of 10 ml aliquot volume. Safety, tolerability and efficacy
      of the inoculation regimens will be evaluated. All 30 volunteers will be evaluated as part of
      an inpatient stay (Days 8-18 post-injection) to diagnose and treat Pf malaria infection with
      chloroquine. Following review, and with the assistance of an independent SMC, 2 regimens will
      be chosen for further testing in DMID 11-0042. The following criteria strategy will be
      employed in the order listed: 1. Regimen necessary to achieve ID100 of adult volunteers; 2.
      Regimen eliciting Pf patency and parasite density (as detected by qRT-PCR) that most closely
      approximates patency rates experienced after mosquito challenge; 3. Regimen requiring the
      least number of injections; 4. Regimen utilizing the fewest number of PfSPZ; 5. Volume of
      administration considered to be the easiest to administer by the clinicians. Chloroquine
      sub-study: Eighteen of thirty participants (3 volunteers from each of the six groups
      comprised of 5-subjects/group) will be assigned to participate in a CQ and possibly
      desethylchloroquine blood and urine study designed to assess the drug kinetics of CQ over the
      course of four weeks after standard CQ dose administration.
    

Intervention name(s): Sanaria™ PfSPZ Vaccine; Chloroquine
Intervention type(s): Biological; Drug
Intervention description(s): 30 subjects in 3 cohorts, 6 groups in different doses of PfSPZ vaccine via the intradermal route. Cohort 1 Medium Dose, Medium Aliquot: Group a: 10,000 PfSPZ in 2 divided doses (e.g., 5000 PfSPZ per 50 microliter (mcL) dose), Group b: 10,000 PfSPZ in 8 divided doses (e.g., 1250 PfSPZ per 50 mcL dose). Cohort 2: Medium dose, Low Aliquot: Group c: 10,000 PfSPZ in 2 divided doses (e.g., 5000 PfSPZ per 10 mcL dose), Group d: 10,000 PfSPZ in 8 divided doses (e.g., 1250 PfSPZ per 10 mcL dose), Cohort 3: High Dose, Low Aliquot; Group e: 50,000 PfSPZ in 2 divided doses (e.g., 25,000 PfSPZ per 10 mcL dose), Group f: 50,000 PfSPZ in 8 divided doses (e.g., 6,250 PfSPZ per 10 mcL dose); Rescue therapy after challenge: 1500 mg chloroquine base orally, over 48 hours (600 mg at time 0 followed by 300 mg oral base at hours 6, 24 and 48)
Intervention MeSH terms: Chloroquine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Keywords: Malaria, vaccine, PfSPZ, challenge