Clinical Trial of the PfSPZ Vaccine
Condition: Plasmodium Falciparum
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the safety and tolerability of a non-replicating,
      metabolically active Plasmodium falciparum sporozoite (PfSPZ) vaccine in malaria-naïve
      healthy volunteers following multiple-dose subcutaneous (SC) or intradermal (ID)
      administration.

      In addition, the investigators wish to evaluate PfSPZ vaccine-mediated protection against P.
      falciparum challenge in the following 4 groups (see below) and compare protective efficacy of
      the PfSPZ vaccine when given by SC v ID administration in all these groups:

        -  Group 1: 4 doses of 7,500 PfSPZ/immunization,

        -  Group 2: 4 doses of 30,000 PfSPZ/immunization,

        -  Group 3: 4 doses of 135,000 PfSPZ/immunization

        -  Group 4: 4 or 6 doses of 135,000 PfSPZ/immunization.

      If > 80% protective efficacy is not achieved in Groups 1, 2, or 3, volunteers in Group 4 will
      receive a fifth and sixth dose.
    

Detailed description: 
      The first clinical trial of the Pf SPZ vaccine is a Phase 1 trial in non-immune healthy adult
      volunteers. Sanaria is the Sponsor and PATH MVI is funding the trial. The study will be
      conducted as a collaborative effort between Sanaria, PATH MVI, the NMRC Malaria Program (U.S.
      Military Malaria Vaccine Program), and the Center for Vaccine Development at the University
      of Maryland at Baltimore (CVD-UMB). The study will take place at the NMRC Malaria Program
      Clinical Trials Center on the campus of the National Naval Medical Center in Bethesda, MD and
      at the CVD and/or General Clinical Research Center, UMB. The study is designed to evaluate
      the safety, tolerability, immunogenicity and protective efficacy of successively higher doses
      of the vaccine administered by the subcutaneous (SC) or intradermal (ID) route.

      There will be 4 groups of volunteers with each group comprised of a subset of volunteers who
      receive the vaccine by the SC route and a subset who receive the vaccine by the ID route.

      Groups 1-3: The first 3 groups will receive 3 ascending doses of vaccine administered as 4 SC
      or ID injections separated by 4 week intervals (7,500 PfSPZ/dose, 30,000 PfSPZ/dose, and
      135,000 PfSPZ/dose respectively). Each of these groups will be challenged a minimum of 3
      weeks after the final dose by exposure to A. stephensi mosquitoes infected with P. falciparum
      sporozoites. All 3 groups will be followed for safety until 48 weeks after the first
      immunization.

      Group 4: Group 4 will start a minimum of 3 weeks after the first immunization of Group 3. If
      there is > 80% efficacy in one or more of the subsets of Groups 1, 2, or 3 (SC or ID), Group
      4 volunteers will receive 4 immunizations (just like Group 3) but will not have experimental
      challenge; they will simply be followed for safety for 12 months after the first
      immunization. The FDA has requested that we follow a group of volunteers receiving the
      highest dose (135 PfSPZ/immunization) without challenge at 3 weeks. However, if there is NOT
      > 80% efficacy in one of more subsets of Groups 1, 2, or 3, after a 6 month observation
      period, Group 4 volunteers will receive two additional monthly immunizations (Immunizations
      #5 and #6) followed by challenge at approximately 3 weeks after the sixth immunization. All
      volunteers in Group 4 will be followed for safety until 52 weeks after the first
      immunization.
    

Intervention name(s): Plasmodium falciparum Sporozoite (strain NF-54; Anopheles stephensi mosquitoes) Vaccine, Live, Inactivated (gamma irradiation)
Intervention type(s): Biological
Intervention description(s): Group 1: 4 doses of 7,500 PfSPZ/immunization,
Group 2: 4 doses of 30,000 PfSPZ/immunization,
Group 3: 4 doses of 135,000 PfSPZ/immunization, and
Group 4: 4 or 6 doses of 135,000 PfSPZ/immunization.
If > 80% protective efficacy is not achieved in Groups 1, 2, or 3, volunteers in Group 4 will receive a fifth and sixth dose.
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Malaria Vaccine; Plasmodium falciparum