A Phase 1 interventional study of PfSPZ-LARC2 Vaccine and PfSPZ Challenge in Malaria (Plasmodium Falciparum), sponsored by Sanaria Inc.. Not yet recruiting at 1 site in Burkina Faso. Open to participants aged 18 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-07-31.
Sponsored by Sanaria Inc. · Phase 1, Interventional, and Prevention
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).
This is a randomized, double-blind, placebo-controlled, single-center Phase 1 clinical trial of PfSPZ-LARC2 Vaccine to be conducted in healthy non-pregnant, non-lactating adults in Burkina Faso. PfSPZ-LARC2 Vaccine is composed of aseptic, purified, vialed, cryopreserved, genetically altered PfNF54 sporozoites (SPZ) that are stored in liquid nitrogen vapor phase (LNVP). After thawing, the vaccine is diluted and administered by direct venous inoculation (DVI).
The trial will compare a low dose of 2x10\^5 PfSPZ to a high dose of 6x10\^5 PfSPZ. There are three groups:
Group 1: one dose of PfSPZ-LARC2 Vaccine (2x10\^5 PfSPZ) Group 2: one dose of PfSPZ-LARC2 Vaccine (6x10\^5 PfSPZ) Group 3: one dose of normal saline placebo
The goal is to have one highly protective group (the high dose group) and one modestly protective group (2x10\^5 PfSPZ) so that there are adequate numbers of protected and non-protected participants to support the secondary and exploratory objectives of identifying immunological correlates of protection. Before study start, if evidence emerges that 4x10\^5 PfSPZ would address the aim of the high dose group (providing high level protection) as effectively as 6x10\^5 PfSPZ, the protocol permits using 4x10\^5 PfSPZ as the higher dose instead of 6x10\^5 PfSPZ.
All participants will be cleared of any existing parasitemia by a three-day treatment course of artemether/lumefantrine (AL). Before treatment, samples will be collected for thick blood smear (TBS) for real-time reading and dried blood spots (DBS) on filter paper for retrospective PCR. Assessment by rapid diagnostic test (RDT) may be included as an option for information purposes. Drug clearance will be done 5-6 weeks before the first dose of investigational product. AL will be administered by study staff using directly observed therapy (DOT).
Following initial clearance, all participants will be checked by TBS two weeks before immunization (DBS sample also collected for retrospective PCR). If a participant is positive by TBS at this timepoint, they will be retreated with the same regimen of AL (or an alternative regimen if clinically appropriate), even if asymptomatic. Because immunization will be done during the dry season when malaria is rarely transmitted, only a few retreatments (if any) may be required two weeks before immunization.
Immunization: TBS/DBS will be checked again on the day of immunization for retrospective reading. On study day 1, group 1 will receive one dose of 2x10\^5 PfSPZ, group 2 will receive one dose of 6x10\^5 PfSPZ, and group 3 will receive one dose of normal saline.
Safety monitoring: Monitoring for adverse events (AEs) will take place for 28 days after injections. 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 immunization. Laboratory tests (white blood count, neutrophil count, lymphocyte count, hemoglobin, platelets, creatinine, alanine aminotransferase and aspartate aminotransferase) will be done on the day of immunization and 7 days after. Medically attended adverse events (MAAEs) and serious adverse events (SAEs) will be monitored throughout the trial.
Surveillance and treatment for malaria post immunization: After vaccine or normal saline injection, surveillance for clinical malaria and malaria infection will be conducted. Although there have been no breakthrough blood stage infections to date in the 68 adults and children receiving PfSPZ-LARC2 Vaccine, breakthrough is still possible. Passive surveillance will be done by encouraging all participants to immediately report any signs or symptoms consistent with malaria to the clinical team, who will be available 24/7. Any symptom consistent with malaria will be 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. TBS will generally be made from finger-prick blood, but venipuncture can be used if preferred by the participant or if venipuncture needs to be done anyway for other tests.
In addition to passive surveillance, TBS/DBS will be obtained from all participants two, four and six weeks after immunization. If any participants are positive for malaria by TBS, they will be treated with AL and if this occurs within 21 days of CHMI, CHMI will be postponed for that participant (or the participant will be excluded from CHMI).
If parasitemia is detected post immunization and prior to CHMI, an additional 2 mL will be collected before treatment, as a back-up for the DBS to be used for the identity assay to differentiate between breakthrough and wildtype infections (this assay was used successfully in the BFSPZL1 trial using blood eluted from DBS). The 2 mL will enable whole genome sequencing if needed.
Surveillance and treatment for malaria post CHMI: Six weeks after vaccine or normal saline injection, participants will undergo CHMI using a dose of 3,200 PfSPZ of PfSPZ Challenge (NF54) administered by DVI. 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. Rapid diagnostic tests (RDTs), if available, may be included as an option for information purposes, although do not provide quantitative estimates of parasite density. Samples will be taken daily starting on day +5 after CHMI until day +18, then every other day until day CHMI+28. On these same days, body temperature will be measured, and malaria symptoms will be solicited. Clinical events will also be recorded. Participants who test positive for malaria will be treated with a three-day oral regimen of dihydroartemisinin-piperaquine (DHA-P). As mentioned, DBS will be collected on filter paper with every TBS, for retrospective analysis by PCR. On day CHMI+28, all participants who have not been treated already will be presumptively treated with the same DHA-P regimen.
All positive TBS endpoints will require retrospective PCR confirmation of Pf parasitemia before being considered final. If samples are negative by PCR, TBS results (and RDT results, if available) will be reviewed. If TBS results are determined to be correct (positive) while PCR is negative, the participant may be excluded from the efficacy analysis due to conflicting data. If TBS results (or RDT results) are determined to represent a false positive result, the participant will be considered negative at the time of treatment. If the time of treatment is later than that of any other participant developing parasitemia post CHMI, the participant will be classified as protected. If the time of treatment is not later than that of any other participant developing parasitemia post CHMI, the participant may be excluded from the efficacy analysis.
Definition of blood stage parasitemia during the immunization up until CHMI: Any positive TBS showing normal appearing malaria parasites at 2/ul or higher will be confirmed by a second reader (with a third reader used to resolve disagreements between the first two). RDT may also be included as an option. TBS will be read in real-time as collected, prioritizing the reading of TBS from symptomatic participants.
Following CHMI, the threshold for declaring a TBS positive will be maintained at 2/ul or higher for symptomatic participants; however, for asymptomatic persons, it will be increased to 1000 parasites/ul to reduce the chance of false positives and unneeded treatment (if false positives occur, the participant will be removed from the efficacy analysis data set and the power of the study would be diminished).
Any participant not already treated post CHMI will be presumptively treated with DHA-P on days 28, 29 and 30 post CHMI.
Last study visit: The last in-person study visit will be 26 weeks after immunization. This will be to record medically significant unsolicited AEs (termed clinical events because the time will be past the 28-day interval for unsolicited AEs) including malaria infections and any medical adverse events.
The study will be conducted by the Groupe de Recherche Action Santé (GRAS) in the Sabou Health District (SHD) area located about 100 km to the west of Ouagadougou, the capital city of Burkina Faso.
As described above, local solicited adverse events will be monitored for 2 days, systemic solicited adverse events for 14 days, and unsolicited adverse events collected daily until 28 days after vaccination. Local (site of injection) adverse events which will be recorded for 2 days after vaccination. In addition, laboratory testing (white blood count, neutrophil count, lymphocyte count, hemoglobin, platelets, creatinine level, alanine aminotransferase, aspartate aminotransferase) will be conducted before and one week after immunization. Serious adverse events (SAEs) and medically attended adverse events (MAAEs) will be recorded from the time of signing the consent to the end of the trial. Pausing rules are defined in the protocol (e.g., a cluster of grade 3 AEs/laboratory abnormalities or an SAE deemed related to the vaccine).
455 studies on the registry are indexed under Malaria, Falciparum; 37 are open to participants now.
This study's planned enrollment of 45 is below the median of 126 across 376 interventional studies indexed under Malaria, Falciparum.
Browse Malaria, Falciparum studies →Sanaria Inc. is the lead sponsor of 29 studies on the registry; 4 are open to participants now.
Of its 10 completed or terminated interventional studies of FDA-regulated products, 3 (30%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
one dose of PfSPZ-LARC2 Vaccine (2x10\^5 PfSPZ)
Biological: PfSPZ-LARC2 Vaccine · Biological: PfSPZ Challenge
one dose of PfSPZ-LARC2 Vaccine (6x10\^5 PfSPZ)
Biological: PfSPZ-LARC2 Vaccine · Biological: PfSPZ Challenge
one dose of normal saline placebo
Biological: PfSPZ Challenge · Other: Normal Saline
PfSPZ-LARC2 Vaccine is composed of aseptic, purified, vialed, cryopreserved, genetically altered PfNF54 sporozoites (SPZ) that are stored in liquid nitrogen vapor phase (LNVP).
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).
saline control comparator
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.
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Study day 1 to Study day 183 (end of study visit)
Humoral immune responses to PfCSP (circumsporozoite protein) after vaccination
Anti-P. falciparum circumsporozoite protein antibody levels measured by ELISA two weeks after vaccination.
Time frame: 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)
Statistical assessment of associations of humoral responses (level of anti-PfCSP antibodies) with protection (frequency of Pf asexual parasitemia) - specifically, the correlation between anti-PfCSP antibody levels, as measured by ELISA two weeks after vaccination, with vaccine efficacy, as measured by frequency of P. falciparum asexual parasitemia in each vaccine group relative to controls after 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.
Time frame: Study day 1 to Study day 71
Plan to share: No
No publications or documents are linked to this record.
Start is estimated for Mar 2027; primary completion for Dec 2027, 9 months later.
Of 49 phase 1 interventional studies under Malaria, Falciparum, half reached primary completion within 13 months of starting (the median), counting those still running; a quarter within 7 and three quarters within 18. This study's planned 9 months is below that.
How these figures are worked out, and which studies are left out of them.
This study is not yet recruiting, as verified in Jul 2026. You cannot join it, but the record below documents what was studied.
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