Randomized, Double-Blind, Placebo-Controlled Trial to Assess Safety, Immunogenicity, and Protective Efficacy Against Naturally Transmitted Plasmodium Falciparum Malaria of One and Two Dose Regimens of a Late Liver Stage-arresting, Replication-competent Plasmodium Falciparum Sporozoite Vaccine (Sanaria® PfSPZ-LARC2 Vaccine) in Healthy Malaria-Exposed Adults in Burkina Faso
This is a phase 2 clinical trial of a Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) vaccine (Sanaria® PfSPZ-LARC2 Vaccine) that will assess field efficacy in Africa. The PfSPZ comprising PfSPZ-LARC2 Vaccine contain a double deletion of the genes encoding the Mei2 and LINUP proteins, both of which are required for transition from liver to blood stage malaria. As a result, mei2-/linup- parasites undergo developmental arrest in the late liver stages without releasing merozoites into the blood stream. No blood stage parasites are produced, either asexual or sexual, and the parasite life cycle does not progress. Because Pf parasites with the LARC phenotype replicate in the liver before disintegrating, they amplify and diversify parasite protein expression and are expected to be a potent immunogen to induce anti-malarial immunity, equaling or exceeding the potency and efficacy of the replication-competent chemo-attenuated Sanaria® PfSPZ-CVac (chloroquine) vaccine approach. Because the parasites are intrinsically attenuated, they are expected to be safe and well tolerated, similar to radiation-attenuated Sanaria® PfSPZ Vaccine, to the replication deficient, early arresting PfSPZ-GA1 Vaccine, and to the single-gene(mei2)-deleted GA2 (LARC1) parasites tested at the Leiden University Medical Center that provided 90% protection against CHMI after a single dose. The active treatments to be assessed for efficacy are one immunization of 6.0x10\^5 PfSPZ or two immunizations with 4.0x10\^5 PfSPZ of PfSPZ-LARC2 Vaccine four weeks apart, timed so that the immunization of the one dose regimen coincides with the second immunization of the two dose regimen. The alternative treatment is immunization with normal saline (placebo group), which is indistinguishable from the test article. The primary variable of interest is whether and when trial participants develop Pf malaria parasitemia during surveillance. Malaria parasitemia will be detected by thick blood smear (TBS), which will be performed every two weeks starting two weeks after the second vaccination (to allow time for the vaccine to work) and extending to week 26 after the second vaccination (24-week surveillance period). Surveillance will continue for 40 weeks but the primary outcome will be determined at 24 weeks of surveillance so the data are comparable to other studies of PfSPZ vaccines.
• Healthy males and females, based on clinical and laboratory findings
• From the age 18 to 50 years
• Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2.
• Residence in the study area for the duration of the study.
• Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study.
• Willingness to be attended to by a study clinician and take all necessary medications prescribed during study period.
• Agreement to provide contact information of a third party household member or close friend to study team.
• Agreement not to participate in another clinical trial during the study period.
• Agreement not to donate blood during the study period (until final clearance is completed)
⁃ Able and willing to complete the study visit schedule over the study follow up period.
⁃ Willingness to undergo HIV, hepatitis B (HBV), hepatitis C (HCV), and sickle cell anemia tests.
⁃ Volunteer participant can demonstrate their understanding of the study by responding correctly to 18 out of 20 true/false statements (in a maximum of two repeat attempts for those who failed to pass in the first attempt).
⁃ Signed written informed consent, in accordance with local practice.
⁃ Has not been treated with any antimalarial medication for at least two weeks prior to the initial clearance treatment.
⁃ Female volunteers aged 18 years and above must be non-pregnant (as demonstrated by a negative urine pregnancy test), and provide consent / assent of their willingness to take protocol-defined measures not to become pregnant during pre-treatment and immunization period and until 28 days after the second immunization. Acceptable measures to not become pregnant include oral or implanted contraceptives, IUD, abstinence, sterilization or sterile sexual partner. Women with a history of surgical or chemical sterilization (e.g., tubal ligation, hysterectomy, other) must provide written documentation of the procedure from a health care provider.
⁃ Demonstration of the ability to complete pre-vaccination drug clearance without significant untoward effects.