PfSPZ-LARC2 Vaccine for Malaria

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

22 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the PfSPZ-LARC2 Vaccine treatment for malaria?

Research shows that the PfSPZ Vaccine, a similar treatment, can provide long-lasting protection against malaria in adults, with up to 100% effectiveness against certain strains. However, its effectiveness in infants is limited, suggesting age and previous malaria exposure may influence the vaccine's success. ^{1 2 3 4 5}

Is the PfSPZ-LARC2 Vaccine for Malaria safe for humans?

The PfSPZ Vaccine, which is similar to the PfSPZ-LARC2 Vaccine, has been tested in over 1,526 people aged 6 months to 65 years in the United States, Europe, and Africa, and has been found to be safe and well tolerated. ^{3 4 6 7 8}

How is the PfSPZ-LARC2 Vaccine treatment for malaria different from other treatments?

The PfSPZ-LARC2 Vaccine is unique because it uses live-attenuated malaria parasites to stimulate the immune system, providing long-lasting protection against different strains of malaria. Unlike other treatments, it is administered intravenously (directly into the vein) and has shown effectiveness in both malaria-naive and experienced individuals. ^{3 4 6 9 10}

What is the purpose of this trial?

This randomized, double-blind, placebo-controlled, Phase 1 trial will enroll up to 22 malaria-naïve, adult participants to test safety, tolerability, immunogenicity, and efficacy of the genetically attenuated Plasmodium falciparum sporozoite vaccine (PfSPZ-LARC2) Vaccine. PfSPZ-LARC2 Vaccine is a late-arresting, replication-competent whole Plasmodium falciparum sporozoite product. We hypothesize that the PfSPZ-LARC2 Vaccine will be safe from breakthrough infection by virtue of deletion of two key parasite genes Mei2 and LINUP and may be more immunogenic and protective than previously tested early arresting sporozoite vaccines. The primary objective is to assess the tolerability and safety of administration of PfSPZ-LARC2 Vaccine, with special attention to the adequacy of attenuation.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

References

1. United States pubmed.ncbi.nlm.nih.gov

Safety, immunogenicity and efficacy of PfSPZ Vaccine against malaria in infants in western Kenya: a double-blind, randomized, placebo-controlled phase 2 trial. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

PfSPZ Vaccine learns a lesson. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Attenuated PfSPZ Vaccine induces strain-transcending T cells and durable protection against heterologous controlled human malaria infection. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Multidose Priming and Delayed Boosting Improve Plasmodium falciparum Sporozoite Vaccine Efficacy Against Heterologous P. falciparum Controlled Human Malaria Infection. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Safety and Differential Antibody and T-Cell Responses to the Plasmodium falciparum Sporozoite Malaria Vaccine, PfSPZ Vaccine, by Age in Tanzanian Adults, Adolescents, Children, and Infants. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Protection against malaria by intravenous immunization with a nonreplicating sporozoite vaccine. [2015]

8. United States pubmed.ncbi.nlm.nih.gov

Increase of Dose Associated With Decrease in Protection Against Controlled Human Malaria Infection by PfSPZ Vaccine in Tanzanian Adults. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Safety and efficacy of PfSPZ Vaccine against Plasmodium falciparum via direct venous inoculation in healthy malaria-exposed adults in Mali: a randomised, double-blind phase 1 trial. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Transient knockdown of Anopheles stephensi LRIM1 using RNAi increases Plasmodium falciparum sporozoite salivary gland infections. [2021]