PfSPZ-LARC2 Vaccine for Malaria

Not currently recruiting at 1 trial location

Overseen By Sean Murphy

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Immunosuppressants, Antimalarials, QT prolongers, others

Disqualifiers: Malaria history, Sickle cell, Seizures, others

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new malaria vaccine to determine its safety and effectiveness in preventing malaria infections. The vaccine uses a weakened version of the malaria parasite, aiming to trigger a strong immune response without causing the disease. Participants will be randomly assigned to receive either the PfSPZ-LARC2 Vaccine or a placebo (a shot with no active ingredients) for comparison. The trial seeks healthy adults between 18 and 45 years old who have never had malaria or participated in a malaria vaccine study. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Will I have to stop taking my current medications?

The trial does not specify that you must stop taking your current medications. However, you cannot use certain medications that have anti-malarial activity or those that interact with the trial drugs. It's best to discuss your specific medications with the trial team to ensure they don't pose any issues.

Is there any evidence suggesting that the PfSPZ-LARC2 Vaccine is likely to be safe for humans?

A previous study showed that the PfSPZ-LARC2 Vaccine is safe for adults. The vaccine was fully weakened, rendering it harmless, and did not cause any malaria infections. Some participants experienced moderate side effects after the second dose, possibly due to the vaccine. These findings suggest the vaccine is generally well-tolerated. However, as this is a Phase 1 trial, the primary goal is to assess safety, and further research will provide clearer information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard malaria treatments that typically involve antimalarial drugs like chloroquine or artemisinin-based therapies, the PfSPZ-LARC2 vaccine is unique because it targets the malaria-causing Plasmodium falciparum sporozoites directly. This vaccine uses a live, attenuated version of the parasite to stimulate a strong immune response, potentially offering long-lasting immunity after just a few doses. Researchers are excited because it could significantly reduce the risk of infection in malaria-naïve individuals, providing a proactive approach to malaria prevention rather than a reactive treatment after infection occurs.

What evidence suggests that the PfSPZ-LARC2 Vaccine might be an effective treatment for malaria?

Studies have shown that the PfSPZ-LARC2 Vaccine, which participants in this trial may receive, shows promise for protecting against malaria. Early findings suggest that the vaccine is safe and does not cause malaria. Research on a similar PfSPZ vaccine showed it could provide up to 90% protection against malaria in a controlled study. This vaccine uses genetically altered malaria parasites that stop growing before they can cause illness. These early results are encouraging and support further testing to evaluate the vaccine's effectiveness. ^{1 3 6 7 8}

Are You a Good Fit for This Trial?

This trial is for malaria-naïve adults aged 18-45 with a BMI of 18.0-35.0 kg/m^2. Participants must consent to study procedures, be available for visits, and use effective contraception if of childbearing potential. Pregnant women or those not using contraception are excluded.

Inclusion Criteria

I have signed a consent form to participate in the study.

I use effective birth control methods or have a vasectomized partner.

I understand and agree to follow the study's procedures and attend all visits.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive the PfSPZ-LARC2 vaccine or placebo on Days 1, 29, and 57

8 weeks

3 visits (in-person)

Controlled Human Malaria Infection (CHMI)

Participants undergo CHMI to measure protective efficacy compared to placebo

4 weeks

1 visit (in-person)

Follow-up

Participants are monitored for adverse events and evidence of blood-stage infection

28 days post-CHMI

What Are the Treatments Tested in This Trial?

Interventions

• PfSPZ-LARC2 Vaccine

Trial Overview The trial tests the PfSPZ-LARC2 Vaccine's safety and effectiveness against malaria in humans. It involves genetically modified Plasmodium falciparum sporozoites administered intravenously, aiming to provide better immunity than previous vaccines.

How Is the Trial Designed?

Group I: Group 3 Experimental Treatment 2 Interventions

Healthy malaria-naïve participants aged between 18 and 45 years will receive 2x10\^5 PfSPZ of Plasmodium falciparum sporozoite vaccine (PfSPZ-LARC2) vaccine on Days 1, 29, and 57 followed by 3.2x10\^3 PfSPZ Challenge (7G8) Controlled Human Malaria Infection (CHMI) on Day 141 administered by direct venous inoculation (DVI). Placebo participants that drop out prior to CHMI will be replaced with infectivity controls. Infectivity controls will receive PfSPZ Challenge (7G8) CHMI N=12

Group II: Group 1 Experimental Treatment 2 Interventions

Healthy malaria-naïve participants aged between 18 and 45 years will receive 2x10\^5 PfSPZ of Plasmodium falciparum sporozoite vaccine (PfSPZ-LARC2) vaccine on Days 1, 29, and 57 followed by 3.2x10\^3 PfSPZ Challenge (7G8) Controlled Human Malaria Infection (CHMI) on Day 169 administered by direct venous inoculation (DVI). Placebo participants that drop out prior to CHMI will be replaced with infectivity controls. Infectivity controls will receive PfSPZ Challenge (7G8) CHMI N=3

Group III: Group 2 Placebo Group 2 Interventions

Healthy malaria-naïve participants aged between 18 and 45 years will receive saline placebo on Days 1, 29, and 57 followed by 3.2x10\^3 PfSPZ Challenge (7G8) Controlled Human Malaria Infection (CHMI) on Day 169 administered by direct venous inoculation (DVI). Placebo participants that drop out prior to CHMI will be replaced with infectivity controls. Infectivity controls will receive PfSPZ Challenge (7G8) CHMI N=1

Group IV: Group 4 Placebo Group 2 Interventions

Healthy malaria-naïve adult participants with no prior history of malaria vaccine study involvement and no exposure to Plasmodium parasites in the past two years, aged between 18 and 45 years will receive saline placebo on Days 1, 29, and 57 followed by 3.2x10\^3 PfSPZ Challenge (7G8) Controlled Human Malaria Infection (CHMI) on Day 141 administered by direct venous inoculation (DVI). Placebo participants that drop out prior to CHMI will be replaced with infectivity controls. Infectivity controls will receive PfSPZ Challenge (7G8) CHMI N=6

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Citations

1. sanaria.com sanaria.com/2025/06/03/sanaria-reports-positive-initial-safety-results-for-groundbreaking-pfspz-larc2-malaria-vaccine/

Sanaria Reports Positive Initial Safety Results for ... Crucially, the initial data in adults confirmed the vaccine was safe, fully attenuated, and caused no malaria infections. Why PfSPZ-LARC2 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06862453?term=vaccine%20paracetamol%20ibuprofen&viewType=Table&rank=5

Safety, Tolerability and Efficacy Against Controlled Human ... Safety, Tolerability and Efficacy Against Controlled Human Malaria Infection of PfSPZ-LARC2 Vaccine in Malaria-naïve Adults (LARC-Tu) · Study Overview · Contacts ...

3. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(25)00434-7/fulltext?rss=yes

a randomised, double-blind, placebo-controlled, phase 2 trial Data from malaria-endemic countries show that PfSPZ Vaccine is safe and well tolerated in infants, children, and adults (age range 5 months ...

4. reporter.nih.gov reporter.nih.gov/project-details/10602357

Progressing PfSPZ vaccines for malaria to licensure and ... The RTS,S/AS01 malaria vaccine, recommended in 2021 by WHO for use in young children, has limited efficacy in preventing malaria hospitalizations (21%) and ...

5. pharmacytimes.com pharmacytimes.com/view/single-dose-malaria-vaccine-demonstrates-90-efficacy-in-early-trials

Single-Dose Malaria Vaccine Demonstrates 90% Efficacy ... Data from a new study showed the vaccine provided 90% protection against controlled human malaria infection after a single injection.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11916963/

Safety, tolerability and immunogenicity of a condensed ... Green datapoints signify the four participants with possible vaccine-induced Grade 2 adverse reactions after the second dose of PfSPZ Vaccine.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1473309925004347

Safety, tolerability, and protective efficacy of a radiation ... Data from malaria-endemic countries show that PfSPZ Vaccine is safe and well tolerated in infants, children, and adults (age range 5 months ...

8. malariaworld.org malariaworld.org/news/sanaria-reports-positive-initial-safety-results-for-groundbreaking-pf-spz-larc-2-malaria-vaccine

Sanaria reports positive initial safety results for ... Crucially, the initial data in adults confirmed the vaccine was safe, fully attenuated, and caused no malaria infections. Read more. Read more.