Challenge Trial of PfSPZ-LARC2 Vaccine in Burkina Faso

NCT07730177 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: BFSPZL3
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, placebo-controlled, Phase 1 trial of Plasmodium falciparum (Pf) late liver stage-arresting replication-competent (LARC) sporozoite (SPZ) malaria vaccine (Sanaria® PfSPZ-LARC2 Vaccine) administered to healthy, malaria-exposed adults by direct venous inoculation (DVI) to determine safety, immunogenicity, and efficacy against controlled human malaria infection (CHMI). 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. CHMI will be performed using PfSPZ Challenge (NF54), composed of PfSPZ that are genetically intact and fully infectious. Because PfSPZ-LARC2 vaccine is also based on the Pf strain NF54, CHMI using PfSPZ Challenge (NF54) is considered homologous to the vaccine. It will be performed 6 weeks after the single administration of PfSPZ-LARC2 Vaccine or normal saline placebo (with an option to shorten the interval to 4 weeks if logistical issues arise, such as a risk that CHMI follow-up will overlap with the rainy season).

Conditions

Malaria (Plasmodium Falciparum)

Keywords

PfSPZ Vaccine; PfSPZ-LARC2 Vaccine; PfSPZ Challenge; CHMI

Outcome Measures

Primary Outcomes (5)

• Efficacy of PfSPZ-LARC2 Vaccine against infection with Plasmodium falciparum malaria (defined as asexual parasitemia) after Controlled Human Malaria Infection (CHMI)

  Frequency of P. falciparum asexual parasitemia in each vaccine group relative to controls after controlled human malaria infection (CHMI). Participants will be followed as outpatients for malaria diagnosis, treatment, and follow-up for four weeks after CHMI until day CHMI+28. Malaria positivity will be determined in real time by TBS microscopy read immediately and with qPCR diagnostics based on concurrent DBS completed retrospectively.

  Study day 43 (day of CHMI) to Study day 71 (28 days after CHMI)

• Safety and tolerability of PfSPZ-LARC2 Vaccine administration in malaria-exposed Burkinabe adults- grade 3 solicited AEs

  Incidence of grade 3 solicited adverse events (AEs) in the 14 days after PfSPZ-LARC2 Vaccine administration

  Study day 1 (day of immunization) to study day 15

• Safety and tolerability of PfSPZ-LARC2 Vaccine administration in malaria-exposed Burkinabe adults- grade 3 unsolicited AEs

  Incidence of grade 3 unsolicited AEs in the 28 days after PfSPZ-LARC2 Vaccine administration

  study day 1 (day of immunization) to study day 29

• Safety and tolerability of PfSPZ-LARC2 Vaccine administration in malaria-exposed Burkinabe adults- grade 3 laboratory AEs

  Incidence of grade 3 abnormal laboratory values one week after PfSPZ-LARC2 Vaccine administration

  study day 1 (day of immunization) to study day 8

• Safety and tolerability of PfSPZ-LARC2 Vaccine administration in malaria-exposed Burkinabe adults- related SAEs

  Incidence of possibly related, probably related or definitely related serious adverse events (SAEs) throughout the study period

  Study day 1 to Study day 183 (end of study visit)

Secondary Outcomes (2)

• Humoral immune responses to PfCSP (circumsporozoite protein) after vaccination

  study day 1 to study day 71

• Correlation of humoral immune responses to PfCSP (anti-PfCSP antibody levels 2 weeks after immunization) with protection (frequency of Pf asexual parasitemia in vaccinees relative to controls after CHMI)

  Study day 1 to Study day 71

Study Arms (3)

Group 1 Low dose Vaccine group

EXPERIMENTAL

one dose of PfSPZ-LARC2 Vaccine (2x10\^5 PfSPZ)

Biological: PfSPZ-LARC2 Vaccine; Biological: PfSPZ Challenge

Group 2 High Dose Vaccine group

EXPERIMENTAL

one dose of PfSPZ-LARC2 Vaccine (6x10\^5 PfSPZ)

Biological: PfSPZ-LARC2 Vaccine; Biological: PfSPZ Challenge

Group 3 control

PLACEBO COMPARATOR

one dose of normal saline placebo

Biological: PfSPZ Challenge; Other: Normal Saline

Interventions

PfSPZ-LARC2 Vaccine BIOLOGICAL

PfSPZ-LARC2 Vaccine is composed of aseptic, purified, vialed, cryopreserved, genetically altered PfNF54 sporozoites (SPZ) that are stored in liquid nitrogen vapor phase (LNVP).

Group 1 Low dose Vaccine group; Group 2 High Dose Vaccine group

PfSPZ Challenge BIOLOGICAL

PfSPZ Challenge (NF54) is composed of PfSPZ that are genetically intact and fully infectious. The aseptic, purified, vialed, cryopreserved PfNF54 sporozoites (SPZ) are stored in liquid nitrogen vapor phase (LNVP).

Group 1 Low dose Vaccine group; Group 2 High Dose Vaccine group; Group 3 control

Normal Saline OTHER

saline control comparator

Group 3 control

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males and females, based on clinical and laboratory findings (note: an effort will be made to recruit roughly equal numbers of males and females, although a balanced sex ratio is not required)
• From 18 to 50 years of age
• Adults with a Body Mass Index (BMI) 18 to 30 Kg/m\^2
• 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 testing
• Able to 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 before the initial clearance treatment.
• Female volunteers 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 the study and safety follow-up period. Acceptable measures to not become pregnant include oral or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner, or sterile sexual partner during the entire study. 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.

You may not qualify if:

• Unable to provide informed consent including inability to pass the test of understanding
• Receipt of a malaria vaccine in a prior clinical trial
• History of a splenectomy or sickle cell disease.
• History of a neurologic disorder (including non-febrile seizures or complex febrile seizures) or formal history of migraine headache
• Current use of systemic immunosuppressant pharmacotherapy
• 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
• Women who are breast-feeding, pregnant or planning to become pregnant during the study period
• Known allergy to artemether-lumefantrine (AL), dihydroartemisinin-piperaquine (DHA-P), or any component of the investigational products
• History of anaphylaxis or other life-threatening reaction to a vaccine
• Participation in any study involving investigational vaccine or drug within 4 weeks before enrollment that in the estimation of the site PI might adversely affect the individual's safety or the quality of data to be collected
• Evidence of increased cardiovascular disease risk; defined as \>10% five-year risk by non-laboratory method
• Plan to participate in another investigational vaccine/drug research during the study
• Plan for major surgery between enrollment until last study visit
• Use or planned use of any drug with anti-malarial activity that would precede or coincide with vaccination through to 56 days after controlled human malaria infection (CHMI)
• 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)

Sponsors & Collaborators

• Sanaria Inc.: lead
• University of Maryland, Baltimore: collaborator
• Seattle Children's Hospital: collaborator
• University of California, Los Angeles: collaborator
• Groupe de Recherche Action en Sante: collaborator

Study Sites (1)

Groupe de Recherche Action en Santé (GRAS)/Unité de Recherche Clinique de Sabou

Ouagadougou, 06, Burkina Faso

Location

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

Saline Solution

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Sodiomon B Sirima, MD PhD

  Groupe de Recherche Action en Sante

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Prof Sodiomon Bienvenu SIRIMA, MD PhD, MD PHD

CONTACT

+226 7020 0444; s.sirima@gras.bf

Dr Alphonse Ouedraogo MD, PhD, MD PhD

CONTACT

+22670140811; a.ouedraogo@gras.bf

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study participants, clinical investigators (including the PI) and all other staff involved in measuring study outcomes will remain blinded to treatment allocation until the data are cleaned and locked. Similarly, Sanaria clinical and regulatory teams will be blinded. The site PI will be responsible for strict maintenance of the blind. Only the Pharmaceutical Operations team responsible for syringe preparation and the unblinded statistician from the data management vendor will be unblinded from the onset of the trial.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: low and high dose of PfSPZ-LARC2 Vaccine

Study Record Dates

• First Submitted: July 16, 2026
• First Posted: July 28, 2026
• Study Start (Estimated): March 1, 2027
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): January 1, 2028
• Last Updated: July 31, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

BU (1)