PfSPZ Vaccine Trial in Malian Children
Condition: Malaria; Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 2

Summary: 
      In this randomized, double-blind, placebo-controlled trial, 268 healthy Malian children aged
      6-10 years, residing in Bancoumana and surrounding villages, will be administered three doses
      of 9.0x10^5 Pf sporozoites (PfSPZ) of PfSPZ Vaccine (or placebo) at 1, 8, and 29-days using
      direct venous inoculation (DVI).

      The study is composed of a single cohort with two arms (categorized by placebo
      control/experimental groups) designed to assess the safety, immunogenicity and protective
      efficacy of PfSPZ Vaccine.

      All subjects will receive artemether-lumefantrine (AL) approximately 1- 2 weeks before the
      first dose of PfSPZ Vaccine or normal saline for clearance of Pf parasitemia. Vaccinated
      participants and non-immunized controls will be followed for safety and monitored for
      development of parasitemia through the natural malaria transmission season to estimate
      vaccine efficacy (VE).
    

Detailed description: 
      This phase 2 study will enroll healthy Malian children between 6 and 10 years of age residing
      in Bancoumana and surrounding villages to participate in a randomized, double blind, placebo-
      controlled study to assess the safety, immunogenicity and protective efficacy of PfSPZ
      Vaccine.

      Participants will be immunized with a 3-dose series of 9.0 x10^5 PfSPZ of PfSPZ Vaccine or
      normal saline (placebo) at 1, 8, and 29 days. Subjects will be screened for eligibility for
      enrollment. Enrollment will begin with AL dosing approximately 1-2 weeks prior to their first
      dose of vaccine. Volunteers will be randomized into two arms (1 vaccine arm, 1 control arm)
      in a 1:1 ratio.

      Vaccinated subjects and controls will then be followed for safety and assessment for malaria
      infection during the subsequent malaria transmission season.

      268 children between the ages of 6 and 10 years old inclusive will be enrolled as follows:

      Arm 1(PfSPZ Vaccine): (n = 134) children ages 6 - 10 will receive three doses of PfSPZ
      Vaccine (9.0x10^5 PfSPZ) via direct venous inoculation (DVI) at 1, 8, and 29 days

      Arm 2 (normal saline): (n = 134) children ages 6 - 10 will receive normal saline via DVI at
      1, 8, and 29 days All subjects will receive artemether-lumefantrine (AL) approximately 1- 2
      weeks before the first dose of PfSPZ Vaccine or normal saline for clearance of Pf
      parasitemia.

      Vaccinated participants and non-vaccinated controls will be monitored for development of Pf
      malaria with symptoms and Pf malaria (parasitemia) through the natural malaria transmission
      season to estimate vaccine efficacy (VE). During the surveillance period, both active and
      passive surveillance will be used to identify Pf malaria with symptoms. Blood smears will be
      made at any time a participant presents with a clinical syndrome consistent with malaria and
      read in real time, with all infections treated.

      In addition, blood smears will be made every four weeks in all participants as active
      surveillance for Pf malaria (parasitemia). However, to avoid confounding the primary clinical
      endpoint, these blood smears will be read retrospectively at the end of the primary
      surveillance period.

      Primary Case Definition:

      Pf malaria with symptoms is defined as a positive thick blood smear at a density of >1000
      parasites/uL (P/uL) plus:

        -  Measured auxiliary temperature ≥ 37.5 degrees Celsius or history of fever (subjective or
           objective) in the last 24 hours, or,

        -  Symptoms of malaria -

             -  Verbal individual (individual able and willing to answer questions): A verbal
                individual is considered symptomatic if reporting at the time of evaluation at
                least two of the following symptoms/symptom groups: headache, chills and/or rigors,
                malaise and/or fatigue, dizziness and/or light-headedness, myalgias and/or
                arthralgias; or

             -  Non-verbal individual (small child or any individual unable or unwilling to answer
                questions): A non-verbal individual is considered symptomatic if manifesting at the
                time of evaluation at least two of the following signs/sign groups: drowsiness,
                irritability and/or fussiness, inability and/or refusal to eat or drink,
                prostration; or

             -  Any individual: Signs of severe malaria (e.g. impairment of consciousness, severe
                anemia, hemoglobinuria, acute kidney injury, etc.)

      Secondary Case Definition:

      Pf malaria with symptoms is defined as a positive thick blood smear at a density of > 0 P/uL
      plus:

        -  Measured axillary temperature ≥ 37.5 degrees Celsius or history of fever (subjective or
           objective) in the last 24 hours, or,

        -  Symptoms of malaria as defined in the primary case definition; or

        -  Meeting criteria for severe malaria

      Pf malaria is defined as:

      - At least one unambiguous asexual parasite on thick blood smear identified by two
      independent microscopists after each examining 0.50 μL of blood in a study participant
    

Intervention name(s): Sanaria® PfSPZ Vaccine; Normal Saline
Intervention type(s): Biological; Other
Intervention description(s): non-adjuvanted, live (metabolically active), radiation-attenuated, non-replicating, whole sporozoite (SPZ) vaccine designed to prevent malaria infection caused by Plasmodium falciparum (Pf).; placebo control- saline
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: randomized, placebo controlled, with concurrent arms
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: PfSPZ Vaccine; Malaria; Plasmodium falciparum