Field Trial of PfSPZ-LARC2 Vaccine in Burkinabe Adults (BFSPZL2)

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.

Study Overview

• Status: Recruiting
• Conditions: Malaria (Plasmodium Falciparum)
• Intervention / Treatment: Biological: Genetically attenuated PfSPZ Vaccine; Other: Normal Saline (0.9% Sodium Chloride)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Prof Sodiomon Bienvenu SIRIMA, MD PhD; Phone Number: +226 7020 0444; Email: s.sirima@gras.bf
• Study Contact Backup: Name: Dr Alphonse Ouedraogo, MD PhD; Phone Number: +22625355690; Email: a.ouedraogo@gras.bf

Study Locations

• Burkina Faso
  • Ouagadougou, Burkina Faso, 06
    • Recruiting
    • Groupe de Recherche Action en Santé (GRAS), Unité de Recherche Clinique de Banfora 06 BP 10248
    • Contact: Prof Sodiomon B SIRIMA, MD PhD; Phone Number: +226 7020 0444; Email: s.sirima@gras.bf

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy males and females, based on clinical and laboratory findings
2. From the age 18 to 50 years
3. Adults with a Body Mass Index (BMI) 18 to 30 Kg/m2.
4. Residence in the study area for the duration of the study.
5. Agreement to release medical information and to inform the study doctor concerning contraindications for participation in the study.
6. Willingness to be attended to by a study clinician and take all necessary medications prescribed during study period.
7. Agreement to provide contact information of a third party household member or close friend to study team.
8. Agreement not to participate in another clinical trial during the study period.
9. Agreement not to donate blood during the study period (until final clearance is completed)
10. Able and willing to complete the study visit schedule over the study follow up period.
11. Willingness to undergo HIV, hepatitis B (HBV), hepatitis C (HCV), and sickle cell anemia tests.
12. 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).
13. Signed written informed consent, in accordance with local practice.
14. Has not been treated with any antimalarial medication for at least two weeks prior to the initial clearance treatment.
15. 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.
16. Demonstration of the ability to complete pre-vaccination drug clearance without significant untoward effects.

Exclusion Criteria:

1. Unable to provide informed consent including inability to pass the test of understanding.
2. Receipt of a malaria vaccine in a prior clinical trial.
3. History of a splenectomy or sickle cell disease.
4. History of a neurologic disorder (including non-febrile seizures or complex febrile seizures) or formal history of migraine headache.
5. Current use of systemic immunosuppressant pharmacotherapy.
6. Receipt of a live vaccine within 4 weeks of first immunization or of 3 or more non-live vaccines within 2 weeks of first immunization.
7. Women who are breast-feeding, pregnant or planning to become pregnant during the study period.
8. Known allergy to artemether-lumefantrine (AL), dihydroartemisinin-piperaquine (DHA-P), or any component of the investigational products.
9. History of anaphylaxis or other life-threatening reaction to a vaccine.
10. Participation in any study involving investigational vaccine or drug within 4 weeks prior to enrollment that in the estimation of the site PI might adversely affect the individual's safety or the quality of data to be collected.
11. Evidence of increased cardiovascular disease risk; defined as >10% five-year risk by non-laboratory method (Gaziano, 2008).
12. Plan to participate in another investigational vaccine/drug research during the study.
13. Plan for major surgery between enrollment until last study visit.
14. Use or planned use of any drug with anti-malarial activity that is not specified by the protocol.
15. Anticipated use of medications known to cause drug interactions with DHA-P (antiarrhythmics, neuroleptics, macrolide antibiotics, fluoroquinolones, imidazole and triazole antifungal agents, quinine, halofantrine, pentamidine and saquinavir, certain non-sedating antihistamines, all of which can affect QT intervals ) or AL (the same list of drugs affecting QT intervals plus rifampin, carbamazepine, phenytoin, St. John's wort and antiretroviral drugs).
16. Positive HIV, HBsAg or HCV serology.
17. History of or evidence for other chronic disease conditions including cancer, diabetes, renal failure, hypertension, tuberculosis, etc.
18. History of arrythmias or cardiac disease, or an abnormal electrocardiogram, defined as one showing prolonged QT interval, pathologic Q waves and significant ST-T wave changes; left ventricular hypertrophy; any non-sinus rhythm including isolated premature ventricular contractions, but excluding isolated premature atrial contractions; right or left bundle branch block; or advanced (secondary or tertiary) A-V heart block; or other clinically significant abnormalities on the electrocardiogram.
19. Any clinically significant deviation from the normal range in biochemistry or hematology tests measured at screening and not resolving (grade 1 abnormalities are allowed).
20. Any medical, psychiatric, social, behavioral or occupational condition or situation (including active alcohol or drug abuse affecting social function) that, in the judgment of the site PI, impairs the participant's ability to give informed consent, increases the risk to the participant of participation in the study, affects the ability of the participant to participate fully in the study, or might negatively impact the quality, consistency, integrity or interpretation of data derived from their participation in the study.
21. Inability to complete a course of malaria treatment prior to receipt of investigational product.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 2 SIngle Dose Vaccine Group; 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; PfSPZ-LARC2 Vaccine is composed of aseptic, purified, vialed, cryopreserved, genetically altered PfNF54 sporozoites (SPZ).; Other: Normal Saline (0.9% Sodium Chloride); The placebo control is normal saline solution (0.9% sodium chloride) and is also administered by DVI.
Experimental: Group 1 Double Dose Vaccine Group; Group 1: two doses of PfSPZ-LARC2 Vaccine (4x10^5 PfSPZ) four weeks apart.	Biological: Genetically attenuated PfSPZ Vaccine; PfSPZ-LARC2 Vaccine is composed of aseptic, purified, vialed, cryopreserved, genetically altered PfNF54 sporozoites (SPZ).
Placebo Comparator: Group 3 Placebo; Group 3: two doses of normal saline placebo four weeks apart.	Other: Normal Saline (0.9% Sodium Chloride); The placebo control is normal saline solution (0.9% sodium chloride) and is also administered by DVI.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	2-24 weeks after last dose of vaccine or placebo

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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	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	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	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; measured axillary temperature ≥ 37.5 degrees Celsius or history of fever in the last 24 hours; or; 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.	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.	Two weeks to 24 weeks after the last immunization
Safety and tolerability of PfSPZ-LARC2 Vaccine- break-through vaccine strain blood stage infections	Incidence of any break-through vaccine strain blood stage infections	After the first administration of vaccine or placebo until the end of the study

Collaborators and Investigators

• Sponsor: Sanaria Inc.
• Collaborators: University of Maryland, Baltimore; University of California, Los Angeles; Seattle Children's Hospital; Fred Hutchinson Cancer Center
• Investigators: Principal Investigator: Sodiomon B Sirima, MD PhD, Groupe de Recherche Action en Sante

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: January 27, 2026
• First Submitted That Met QC Criteria: January 27, 2026
• First Posted (Actual): February 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 1, 2026
• Last Update Submitted That Met QC Criteria: May 28, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: PfSPZ Vaccine; Plasmodium falciparum; malaria; PfSPZ-LARC2 Vaccine
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Parasitic Diseases; Malaria; Malaria, Falciparum; Pharmaceutical Preparations; Inorganic Chemicals; Chlorine Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Sodium Compounds; Chlorides; Hydrochloric Acid; Saline Solution; Sodium Chloride
• Other Study ID Numbers: BFSPZL2; 6003.04 (Other Grant/Funding Number: Gates Foundation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No