Safety, Tolerability and Efficacy of PfSPZ Vaccine Against Heterologous CHMI in US Malaria naïve Adults
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a randomized, double blind, placebo-controlled, single site, trial of a condensed
      regimen of PfSPZ Vaccine administered on Days 1, 8 and 29 by direct venous inoculation (DVI)
      to assess safety, tolerability, immunogenicity and vaccine efficacy (VE) against heterologous
      controlled human malaria infection (CHMI) conducted at varying time intervals after the third
      immunization (14, 42 or 70 days). The trial is designed to simulate pre-deployment
      immunization of military personnel. Prior studies with this regimen show high level
      protection (>80%) against CHMI at 21 days, but the onset and duration of protection have not
      been fully defined.
    

Detailed description: 
      USSPZV6 is a single site, double-blind, randomized, placebo-controlled, clinical trial. Study
      groups will be randomized in a 14:4 ratio (vaccine to NS placebo) among healthy,
      malaria-naive adults aged 18-50 years. There will be three groups of subjects. Each of the 3
      groups will have 14 subjects who receive 3 injections with 9 x 10^5 PfSPZ of PfSPZ Vaccine
      and 4 subjects who receive 3 injections with normal saline placebo. Subjects who complete all
      immunizations will receive a total 2.7 x 10^6 PfSPZ. VE will be assessed by exposure to PfSPZ
      Challenge (7G8) (cryopreserved infectious sporozoites originating from a Pf strain isolated
      in Brazil, and thus heterologous to the vaccine). The day of CHMI will vary per group with
      Groups A, B and C receiving PfSPZ Challenge (7G8) on days 14, 42 or 70 after Vaccination 3
      (V3), respectively. Direct observation will be for 30 minutes following each dose of PfSPZ
      Vaccine or PfSPZ Challenge. A research/safety monitor and a Safety Monitoring Committee (SMC)
      will provide safety oversight. Clinical study monitoring will be the responsibility of
      Sanaria or Sanaria's designated and authorized representative. Screening will not precede
      enrollment by more than 90 days. For the second and third immunizations, allowable windows
      are assigned. The entire study will take approximately 8 months to complete, including 2
      months of recruitment because the study will be conducted in two sequential cohorts. The
      period of follow-up for each immunized subject and placebo controls is through 8 weeks
      post-CHMI. Study participation will last between 99 and 154 days (not including screening)
      depending upon group assignment.

      Case report forms (CRFs) will serve as the repository of source documents and other relevant
      data for each study subject. Only information that cannot be collected initially into the CRF
      (for instance, EKGs and AE medical records) will first be collected onto separate source
      documents before transcription into the CRF. Laboratory results will be entered from source
      documents directly into the database.

      Solicited adverse events (AEs) will be collected for 7 days after each immunization.
      Unsolicited AEs will be collected from the first immunization (V1) until 28 days after the
      third immunization (V3) and for 28 days after CHMI. Physical exams and medical history will
      be assessed as indicated. Safety laboratories will be collected at screening, day of V1, 14
      days after V2, 7 days after V3, day of CHMI and 28 days after CHMI. Surveillance for SAEs
      will occur for the duration of the study. Follow-up of AEs (including SAEs) occurs until
      resolution or stability.

      If clinical laboratories expire (meaning they were obtained greater than 90 days prior to
      planned enrollment), specific safety labs will be repeated for screening purposes. Safety
      evaluation includes an electrocardiogram (ECG) performed at screening. Subjects with abnormal
      cardiovascular symptoms or findings that appear clinically significant will be excluded and
      if appropriate, referred to a cardiologist for further evaluation.Clinical laboratory
      testings will be conducted by Fred Hutchinson Cancer Research Center.

      Detection of parasitemia post CHMI will be based upon qRT-PCR. Subjects who have 2 positive
      qRT-PCR results separated by greater than or equal to 12 hours or a single qRT-PCR result
      reading > 250 estimated parasites/mL will be treated with anti-malaria therapy. Anti-malarial
      therapy will consist of: First-line: Malarone, Second-line: Coartem.
    

Intervention name(s): PfSPZ Vaccine; PfSPZ Challenge (7G8) for CHMI; Normal Saline
Intervention type(s): Biological; Biological; Other
Intervention description(s): Metabolically active, non-replicating, radiation attenuated, aseptic, purified, cryopreserved NF54 P. falciparum (Pf) sporozoites (PfSPZ Vaccine); Live, infectious, aseptic, purified, vialed, cryopreserved, Plasmodium falciparum sporozoites, strain 7G8; normal saline placebo control
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: PfSPZ Vaccine; Malaria; Plasmodium falciparum; Controlled human malaria infection