A Phase 2 interventional study of Genetically attenuated PfSPZ Vaccine and Normal Saline (0.9% Sodium Chloride) in Malaria (Plasmodium Falciparum), sponsored by Sanaria Inc.. Recruiting at 1 site in Burkina Faso. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-01.
Sponsored by Sanaria Inc. · Phase 2, Interventional, and Prevention
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.
This is a randomized, double-blind, placebo-controlled, single-center phase 2 clinical trial in healthy adults.
The trial will compare a single dose regimen (6x10\^5 PfSPZ administered once) to a two dose regimen (4x10\^5 PfSPZ administered twice). There are three groups:
Group 1: two doses of PfSPZ-LARC2 Vaccine (4x10\^5 PfSPZ) four weeks apart.
Group 2: one dose of normal saline placebo and one dose of PfSPZ-LARC2 Vaccine (6x10\^5 PfSPZ) four weeks apart.
Group 3: two doses of normal saline placebo four weeks apart.
All participants will be cleared of any existing parasitemia by (minimally) a three day treatment course of artemether /lumefantrine. This will be done 5-6 weeks prior to the first dose of investigational product, to prevent the known immunosuppressive effects of parasitemia on the induction of protective immunity and to prevent such infections from recrudescing later in the trial. If, at a pre-immunization visit 2 weeks before the first dose, any participant is positive by TBS, they will be retreated with the same regimen of artemether/lumefantrine. Clearance will be repeated 2 weeks before the second dose in all participants.
For the first immunization (V1), group 1 will receive one dose of vaccine (4x10\^5 PfSPZ) and groups 2 and 3 will receive one dose of normal saline (NS placebo). Four weeks later, group 1 will receive a second dose of vaccine (4x10\^5 PfSPZ), group 2 will receive a first dose of vaccine (6x10\^5 PfSPZ) and group 3 will receive a second dose of normal saline. A syringe of vaccine and a syringe of normal saline are indistinguishable, facilitating the double-blind design. All administrations will be by direct venous inoculation (DVI).
Monitoring for adverse events (AEs) will take place during the 28-day interval between immunizations and for 28 days after the second immunization (56 days in total). Local (site of injection) AEs will be solicited for two days, systemic AEs will be solicited for 14 days and unsolicited AEs will be collected for 28 days after each immunization. In addition, participants will be instructed to notify the clinical team day or night should symptoms suggestive of malaria develop. Any symptoms consistent with malaria will be immediately investigated by TBS, which will be repeated if symptoms are ongoing - daily if the initial TBS is negative and symptoms are grade 1 or 2 in severity, or every 8 to 12 hours if initial TBS is negative and symptoms are grade 3 in severity. Malaria signs and symptoms include fever (axillary temperature in > 37.5°C [>99.5°F]), subjective fever, headache, dizziness, malaise, fatigue, chills, rigors, sweats, myalgia, arthralgia, nausea, vomiting, diarrhea, abdominal pain, cough and chest pain. Finally, medically-attended adverse events (MAAEs) and serious adverse events (SAEs) will be monitored throughout the trial. Laboratory tests (white blood count, neutrophil count, lymphocyte count, hemoglobin, platelets, creatinine, alanine aminotransferase) will be done on the day of each immunization and 7 days after each immunization.
Two weeks following immunization, active and passive surveillance for clinical malaria and malaria infection will begin. Passive detection will be achieved by encouraging all participants to immediately report any signs or symptoms consistent with malaria to the clinical team, which will be available 24/7. A TBS will be obtained as quickly as possible and read.
Active surveillance will consist of obtaining a TBS every two weeks from the entire study cohort starting two weeks after the second immunization, regardless of symptoms. These will be read in real-time only if there are malaria signs and symptoms. At each two week visit, participants will be reminded of the importance of contacting the clinical team if they develop malaria symptoms. The primary efficacy endpoint will be after 24 weeks of surveillance (26 weeks after immunization). Efficacy will also be calculated after the full 40 weeks of follow-up.
Surveillance will continue past the 24 week primary endpoint until at least 40 weeks, with an option to continue for a second season of surveillance if merited by efficacy demonstrated during the first rainy season and identification of funding for additional follow-up. If there is no continuation, the last study visit will be at 40 weeks of surveillance (42 weeks after second immunization).
At each two week visit when blood is sampled for TBS and at any time that TBS is made for the purpose of diagnosing clinical malaria, dried blood spots will be collected for possible later analysis by qPCR as an exploratory objective.
Prior to treating any malaria infection, blood samples will be obtained to allow for conducting genetic analyses of parasites. After treatment for malaria, 28 days of person-time at risk will be discounted (because of protection afforded by piperaquine), and then surveillance will continue to collect data on any additional parasitemias or clinical cases.
Exclusion Criteria:
Group 2: one dose of normal saline placebo and one dose of PfSPZ-LARC2 Vaccine (6x10\^5 PfSPZ) four weeks apart.
Biological: Genetically attenuated PfSPZ Vaccine · Other: Normal Saline (0.9% Sodium Chloride)
Group 1: two doses of PfSPZ-LARC2 Vaccine (4x10\^5 PfSPZ) four weeks apart.
Biological: Genetically attenuated PfSPZ Vaccine
Group 3: two doses of normal saline placebo four weeks apart.
Other: Normal Saline (0.9% Sodium Chloride)
PfSPZ-LARC2 Vaccine is composed of aseptic, purified, vialed, cryopreserved, genetically altered PfNF54 sporozoites (SPZ).
The placebo control is normal saline solution (0.9% sodium chloride) and is also administered by DVI.
Vaccine efficacy of PfSPZ-LARC2 Vaccine as compared to normal saline, placebo against first Pf infection as detected by thick blood smear (TBS).
TBS positive for asexual Pf at any parasite density collected every 2 weeks and at any time participants present with symptoms of malaria, starting 2 weeks after last dose of vaccine or placebo and extending 24 additional weeks.
Time frame: 2-24 weeks after last dose of vaccine or placebo
Safety and tolerability of PfSPZ-LARC2 Vaccine - solicited AEs
Incidence of grade 3 solicited adverse events (AEs) in the 14 days post each administration of vaccine or placebo
Time frame: 14 days post each administration of vaccine or placebo
Safety and tolerability of PfSPZ-LARC2 Vaccine- laboratory abnormalities
Incidence of laboratory abnormalities at 1 week post each administration of vaccine or placebo
Time frame: 1 week post each administration of vaccine or placebo
Safety and tolerability of PfSPZ-LARC2 Vaccine- unsolicited AEs
Incidence of related grade 3 unsolicited AEs in the 28 days post each administration of vaccine or placebo
Time frame: 28 days post each administration of vaccine or placebo
Safety and tolerability of PfSPZ-LARC2 Vaccine- SAEs
Incidence of related serious adverse events (SAEs) after the first administration of vaccine or placebo until the end of the study
Time frame: After the first administration of vaccine or placebo until the end of the study
Safety and tolerability of PfSPZ-LARC2 Vaccine- break-through vaccine strain blood stage infections
Incidence of any break-through vaccine strain blood stage infections
Time frame: After the first administration of vaccine or placebo until the end of the study
Vaccine efficacy against naturally transmitted first Pf clinical malaria
Assess incidence of clinical malaria (primary case definition): Positive TBS at any parasite density plus 1. measured axillary temperature ≥ 37.5 degrees Celsius or history of fever in the last 24 hours; or 2. at least two of the following symptoms/ symptom groups: headache; chills and/or rigors; malaise and/or fatigue; dizziness and/or lightheadedness; myalgias and/or arthralgias; or (c) meeting criteria for severe malaria.
Time frame: 2 weeks after last dose of vaccine or placebo and extending 24 additional weeks.
Antibody responses following vaccination and their association with vaccine efficacy
Anti-Plasmodium falciparum (Pf) circumsporozoite protein (CSP) antibody levels measured by ELISA before immunization, at least two weeks and 24 weeks after the last immunization and the association of these levels with vaccine efficacy against Pf infection and/or Pf clinical malaria.
Time frame: Two weeks to 24 weeks after the last immunization
Plan to share: No
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Sanaria Inc.