PfSPZ-LARC2 Vaccine for Malaria

Recruiting at 1 trial location

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

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

Trial Summary

What is the purpose of this trial?

This is a randomized, double-blind, placebo-controlled, two-part Phase 1 trial that will enroll up to 40 malaria-naïve adult participants to test safety, tolerability, immunogenicity, and efficacy of the genetically attenuated Plasmodium falciparum sporozoite vaccine (PfSPZ-LARC2) Vaccine administered by direct venous inoculation (DVI). PfSPZ-LARC2 Vaccine consists of late-arresting, replication-competent, cryopreserved Plasmodium falciparum sporozoites that are genetically attenuated. 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 am a man or a non-pregnant woman aged 18 to 45.

Treatment Details

Interventions

• PfSPZ-LARC2 Vaccine (Cancer 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: Arm 1 Part 2 Group 7 Experimental Treatment 2 Interventions

Healthy malaria-naïve participants aged between 18 and 45 years will receive 4x10\^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). Selection Criteria for Part 2 based on protection outcomes in Part 1 (protection = no evidence of infection by qRT-PCR endpoint after CHMI for vaccinated participants) N=15

Group II: Arm 1 Part 2 Group 6 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). Selection Criteria for Part 2 based on protection outcomes in Part 1 (protection = no evidence of infection by qRT-PCR endpoint after CHMI for vaccinated participants) N=3

Group III: Arm 1 Part 2 Group 5 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 followed by 3.2x10\^3 PfSPZ Challenge (7G8) Controlled Human Malaria Infection (CHMI) on Day 113 administered by direct venous inoculation (DVI). Selection Criteria for Part 2 based on protection outcomes in Part 1 (protection = no evidence of infection by qRT-PCR endpoint after CHMI for vaccinated participants) N=15

Group IV: Arm 1 Part 1 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 V: Arm 1 Part 1 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 VI: Arm 2 Part 1 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 VII: Arm 2 Part 1 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

Group VIII: Arm 2 Part 2 Group 8 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 Challenge (7G8) Controlled Human Malaria Infection (CHMI) on Day 141 administered by direct venous inoculation (DVI). Selection Criteria for Part 2 based on protection outcomes in Part 1 (protection = no evidence of infection by qRT-PCR endpoint after CHMI for vaccinated participants) N=3

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+