PfSPZ Vaccine Trial in Malian Children
Condition: Malaria; Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Intervention: Sanaria® PfSPZ Vaccine; Normal Saline
Intervention description: 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
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: randomized, placebo controlled, with concurrent arms
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking description: double-blinded
Enrollment: 290.0
Sex: All
Minimum age: 6 Years
Maximum age: 10 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: PfSPZ Vaccine; Malaria; Plasmodium falciparum

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).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Parent(s) or guardian(s) willing and able to provide consent prior to initiation of
             any study procedures

          2. Stated willingness of parent(s) or guardian(s) to comply with all study procedures and
             availability for the duration of the study

          3. Malaria comprehension exam completed by parent(s) or guardian(s) and passed with a
             score of ≥80% or per investigator's discretion

          4. Healthy children 6-10 years of age at enrollment (inclusive)

          5. Parent(s) or guardian(s) are able to provide proof of identity to the satisfaction of
             the study clinician completing the enrollment process

          6. Willing to have blood samples stored for future research

        Exclusion Criteria:

          1. Medical, behavioral, cognitive, or psychiatric disease that in the opinion of the
             investigator affects the ability of the participant's parent and/or legal guardian to
             understand and comply with the study protocol

          2. Menstruating females (in order to avoid cultural implications of further assessing
             pregnancy potential i.e. sexual activity in this age group)

          3. Hemoglobin (Hgb), WBC, absolute neutrophils, and platelets outside the local
             laboratory-defined limits of normal and ≥ Grade 2 (subjects may be included at the
             investigator's discretion for 'not clinically significant' abnormal values)

          4. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined
             upper limit of normal and ≥ Grade 2 (subjects may be included at the investigator's
             discretion for 'not clinically significant' abnormal values)

          5. Infected with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C

          6. Sickle cell disease by history

          7. Taking or planning to take seasonal malaria chemoprophylaxis

          8. Clinically significant abnormal electrocardiogram (ECG) such as abnormal QTc

          9. History of receipt of the following:

               -  Investigational malaria vaccine in the last 2 years

               -  Immunoglobulins and/or blood products within 6 months of enrollment

               -  Investigational product within 3 months of enrollment

               -  Chronic (≥14 days) oral or IV corticosteroids (excluding topical or nasal) at
                  immunosuppressive doses (i.e., prednisone ≥20 mg/day or equivalent) or
                  immunosuppressive drugs within 30 days of enrollment

               -  Live vaccine within 30 days of enrollment

               -  Killed vaccine within 14 days of enrollment or planned receipt of a killed
                  vaccine within 14 days of scheduled vaccination

         10. Known medical problems:

               -  Pre-existing autoimmune or antibody-mediated diseases (e.g. systemic lupus
                  erythematosus, rheumatoid arthritis, multiple sclerosis, Sjögren's syndrome, or
                  autoimmune thrombocytopenia)

               -  Severe asthma (defined as asthma that is unstable or required emergent care,
                  urgent care, hospitalization, or intubation during the past two years, or that
                  has required the use of oral or parenteral corticosteroids at any time during the
                  past two years)

               -  Immunodeficiency disorder

               -  Asplenia or functional asplenia

               -  Diabetes

               -  Deep venous thrombosis or thromboembolic event

               -  Seizures (exception is simple febrile seizures during childhood)

         11. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine,
             rheumatologic, autoimmune, hematological, oncologic, or renal disease by history,
             physical examination, and/or laboratory studies