Safety, Immunogenicity, and Protective Efficacy of Two Regimens of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Natural Transmission Season in Healthy African Adults in Mali
Condition: Malaria
MeSH terms: Malaria
Intervention: PfSPZ Vaccine; Normal Saline; artemether 20mg/lumefantrine 120mg (AL)
Intervention description: PfSPZ Vaccine is Radiation attenuated, aseptic, purified, vialed, cryopreserved, NF54 P. falciparum sporozoites produced by Sanaria, Inc.; Clear liquid indistinguishable from the study product will be used as a placebo rather than a comparator vaccine.; Licensed antimalarial in the US and Mali for use for uncomplicated malaria.
Intervention MeSH terms: Lumefantrine; Artemether
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 478.0
Sex: All
Minimum age: 18 Years
Maximum age: 35 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: PfSPZ Vaccine; Malaria; Plasmodium falciparum

Summary:

      Background:

      The disease malaria affects many people in Mali and other parts of Africa and the world. It
      is caused by germs spread by mosquito bites. Malaria may be mild. But it can also be serious
      or lead to death if it is not treated promptly. Researchers want to find a safe vaccine that
      prevents malaria.

      Objective:

      To study how safe and tolerable the malaria vaccine called PfSPZ Vaccine is for healthy
      adults.

      Eligibility:

      Healthy adults:

        -  ages 18-35 in Ouelessebougou, Mali

        -  not infected with HIV, hepatitis B, or hepatitis C

        -  for females, not pregnant or breastfeeding and must use reliable birth control during
           the study

      Design:

      Participants will be screened with questions about malaria and will undergo blood, urine, and
      heart tests.

      Participants will be randomly assigned to 1 of 4 groups. They will get injections of either
      the PfSPZ Vaccine or a salt-water placebo. They will not know which one they get.

      Vaccinations will occur leading into the malaria transmission each year with 3 injections
      leading into Year 1 (malaria transmission season in 2018) and 1 injection prior to Year 2
      (malaria transmission season 2019).

      One vaccine group and one placebo group will get an injection 3 times over 4 weeks with an
      additional vaccination ~10 months later.

      The other two groups (vaccine group and placebo) will get an injection 3 times over 16 weeks
      with an additional vaccination ~10 months later.

      All participants will be treated with an antimalarial medication prior to the third injection
      and prior to fourth injection.

      They will be followed for approximately 6 months after third and fourth injection.

      At vaccine visits, female participants will have a pregnancy test before injection. All
      participants will have an arm cleaned and the vaccine injected in a vein. They will be
      watched for 30 minutes.

      At non-vaccine visits, participants will have a physical exam and be asked how they are
      feeling. They will usually have blood tests.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

               1. Age greater than or equal to 18 and less than or equal to 35 years

               2. Able to provide proof of identity to the satisfaction of the study clinician
                  completing the enrollment process

               3. In good general health and without clinically significant medical history

               4. Willing to have blood samples stored for future research

               5. Available for the duration of the study

               6. Females of childbearing potential must be willing to use reliable contraception
                  (as defined below) from 21 days prior to Study Day 1 to 28 days after last
                  vaccination.

                    -  Reliable methods of birth control include:

                         -  one of the following: confirmed pharmacologic contraceptives
                            (parenteral) delivery; intrauterine or implantable device. OR

                         -  two of the following: a documented oral or transdermal or vaginal ring
                            contraceptives; PLUS condoms with spermicide or diaphragm with
                            spermicide.

                    -  Note, Coartem (artemether specifically) may reduce the effectiveness of
                       systemic hormonal contraceptives, therefore additional barrier methods such
                       as condoms must also be used during the 3 days of Coartem dosing.

                    -  Women who are not able to get pregnant will also be required to report date
                       of last menstrual period, history of surgical sterility (i.e. tubal
                       ligation, hysterectomy) or premature ovarian insufficiency (POI), and will
                       have urine or serum pregnancy test performed per protocol.

        EXCLUSION CRITERIA:

          1. Pregnancy, as determined by a positive urine or serum human chorionic gonadotropin
             (beta-hCG) test (if female). NOTE: Pregnancy is also a criterion for discontinuation
             of any further dosing or non-safety related interventions for that subject.

          2. Currently breast-feeding (if female)

          3. Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator
             affects the ability of the participant to understand and comply with the study
             protocol

          4. Hemoglobin (Hb), WBC, absolute neutrophils, and platelets outside the local
             laboratory- defined limits of normal (subjects may be included at the investigator s
             discretion for not clinically significant values)

          5. Alanine transaminase (ALT) or creatinine (Cr) level above the local laboratory-defined
             upper limit of normal (subjects may be included at the investigator s discretion for
             not clinically significant values)

          6. Infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or
             hepatitis B (HBV)

          7. Known or documented sickle cell disease by history (Note: known sickle cell trait is
             NOT exclusionary)

          8. Clinically significant abnormal electrocardiogram (ECG) such as abnormal QTc.

          9. Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, endocrine,
             rheumatologic, autoimmune, hematological, oncologic, or renal disease by history,
             physical examination, and/or laboratory studies including urinalysis

         10. History of receiving any investigational product within the past 30 days

         11. Participation or planned participation in a clinical trial with an investigational
             product prior to completion of the follow-up visit 28 days following last vaccination
             OR planned participation in an investigational vaccine study until the last required
             protocol visit

         12. Medical, occupational, or family problems as a result of alcohol or illicit drug use
             during the past 12 months

         13. History of a severe allergic reaction(Grade 3 or higher or per PI discretion) or
             anaphylaxis

         14. 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)

         15. Pre-existing autoimmune or antibody-mediated diseases including but not limited to:
             systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's
             syndrome, or autoimmune thrombocytopenia

         16. Known immunodeficiency syndrome

         17. Known asplenia or functional asplenia

         18. Use of:

               -  Chronic (greater than or equal to 14 days) oral or IV corticosteroids (excluding
                  topical or nasal) at immunosuppressive doses (i.e., prednisone >10 mg/day) or
                  immunosuppressive drugs within 30 days of vaccination

               -  Use of antimalarials or systemic antibiotics with known antimalarial activity
                  within 5 drug half-lives prior to the first vaccine (such as artemether,
                  artemether-lumefantrine, sulfadoxine-pyrimethamine,
                  trimethoprim-sulfamethoxazole, doxycycline, tetracycline, clindamycin,
                  erythromycin, fluoroquinolones or azithromycin)

         19. Receipt of a live vaccine within the past four weeks or a killed vaccine within the
             past two weeks prior to Vaccination #1 and every subsequent vaccination day

         20. Receipt of immunoglobulins and/or blood products within the past six months

         21. Previous receipt of an investigational malaria vaccine in the last five years

         22. Known allergies or other contraindications against Coartem

         23. Other condition(s) that, in the opinion of the investigator, would jeopardize the
             safety or rights of a participant participating in the trial, interfere with the
             evaluation of the study objectives, or would render the subject unable to comply with
             the protocol