Study of Safety and Effectiveness of Intravenous Immunization With PfSPZ Vaccine in Healthy African Adults
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Malaria is caused by small germs carried by mosquitoes. People can get malaria if an
      infected mosquito bites them. Malaria destroys red blood cells and reduces oxygen in the
      blood. Most malaria is mild, but severe malaria kills at least 660,000 people each year.
      About 75% of these are children in Sub-Saharan Africa, most under age 5. Researchers want to
      find a safe vaccine that helps prevent malaria.

      Objectives:

      - To see if a new malaria vaccine is well tolerated and effective.

      Eligibility:

      - Healthy adults 18 35 years old who are not pregnant and live in Mali.

      Design:

        -  Participants will be screened with medical history, physical exam, and blood test. They
           will also have an ECG. Soft electrodes will be stuck to the skin. A machine will record
           the heart s electrical signals.

        -  Study participation will last about 1 year.

        -  Participants will be randomly placed in 5 groups. Some will get 2 doses of the PfSPZ
           vaccine weeks apart; some will get 3 or 5 doses of vaccine; some will get 3 or 5 doses
           of placebo.

        -  Doses will be given through a needle in the arm directly into the bloodstream. Then
           participants must stay at the clinic for 2 hours.

        -  After each dose, participants will return to the clinic several times for blood tests
           and physical exam.

        -  A week before the first dose and 2 weeks after the last, participants will take a full
           course of anti-malaria drugs.

        -  If a participant gets malaria during the study, they will take another course of
           anti-malaria drugs.
    

Detailed description: 
      For decades it is known that humans can be protected against malaria by repeated immunization
      with radiation-attenuated sporozoites. Traditionally, those sporozoites are administered by
      exposing the vaccinee to at least 1000 bites of sporozoite-infected irradiated mosquitoes, an
      approach that is unsuitable for mass vaccination campaigns. Recently, Sanaria Inc. 1 has
      developed a process for manufacturing, in compliance with current Good Manufacturing
      Practices (cGMPs) aseptic, purified, radiation attenuated cryopreserved sporozoites from a
      wellcharacterized isolate of P. falciparum. This product, which is called PfSPZ Vaccine, can
      be administered by needle and syringe. Previous studies conducted by the Vaccine Research
      Center, National Institutes of Health (NIH) and the Navy have established that IV
      administration of PfSPZ Vaccine can induce sterile protection against controlled human
      malaria infection (CHMI) with a homologous strain of P. falciparum in up to 100% of malaria
      na(SqrRoot) ve individuals.

      The next logical step is to test the safety and immunogenicity of PfSPZ Vaccine in malaria
      experienced individuals. As an exploratory objective, this study will collect initial data to
      find out if the vaccine can protect against naturally occurring infection. Here, we propose a
      randomized double blind controlled trial to assess the safety and immunogenicity of IV
      administration of PfSPZ Vaccine in African adults.

      Subjects will be recruited from a rural village in Mali. The study will be conducted as
      collaboration among the Malaria Research and Training Center (MRTC, Mali), the Laboratory of
      Malaria Immunology and Vaccinology (LMIV) National Institute of Allergy and Infectious
      Diseases (NIAID), and Sanaria, Inc. Group 1 (n=12), will receive 135,000 PfSPZ Vaccine,
      followed by 270,000 PfSPZ Vaccine 2 weeks later for safety purposes. An independent Data
      Safety Monitoring Board (DSMB) will determine whether it is safe to proceed with 270,000
      PfSPZ Vaccine.

      At Study Week 4, Group 4 (n=50) will receive their first of 5 doses of 270,000 PfSPZ Vaccine
      given at 4, 8, 12, 16, and 24 weeks, alongside Group 5 (n=50) receiving a similar volume
      placebo. Safety data will be collected at defined time points after each immunization. From
      Week 28 until Week 48 all subjects will be monitored for parasitemia detected by slide
      microscopy every 14 days and by passive case detection.
    

Intervention name(s): PfSPZ Vaccine; Placebo
Intervention type(s): Biological; Drug
Intervention description(s): Aseptic, purified, vialed, cryopreserved, radiation attenuated NF54 p.falciparum sporozoites produced by Sanaria, Inc.; Placebo
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Randomized; Double Blinded; Mali; Malaria; Transmission