NCT03510481

Safety, Immunogenicity, and Protective Efficacy of Two Regimens of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Natural Transmission Season in Healthy African Adults in Mali

Randomized, Placebo-Controlled, Double-Blind Study to Assess Safety, Immunogenicity, and Protective Efficacy of Two Regimens of Radiation Attenuated Plasmodium Falciparum NF54 Sporozoites (PfSPZ Vaccine) During Natural Transmission Season in Healthy African Adults in Mali

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 478 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

Background: The disease malaria affects many people in Mali and other parts of Africa and the world. It is caused by germs spread by mosquito bites. Malaria may be mild. But it can also be serious or lead to death if it is not treated promptly. Researchers want to find a safe vaccine that prevents malaria. Objective: To study how safe and tolerable the malaria vaccine called PfSPZ Vaccine is for healthy adults. Eligibility: Healthy adults: * ages 18-35 in Ouelessebougou, Mali * not infected with HIV, hepatitis B, or hepatitis C * for females, not pregnant or breastfeeding and must use reliable birth control during the study Design: Participants will be screened with questions about malaria and will undergo blood, urine, and heart tests. Participants will be randomly assigned to 1 of 4 groups. They will get injections of either the PfSPZ Vaccine or a salt-water placebo. They will not know which one they get. Vaccinations will occur leading into the malaria transmission each year with 3 injections leading into Year 1 (malaria transmission season in 2018) and 1 injection prior to Year 2 (malaria transmission season 2019). One vaccine group and one placebo group will get an injection 3 times over 4 weeks with an additional vaccination \~10 months later. The other two groups (vaccine group and placebo) will get an injection 3 times over 16 weeks with an additional vaccination \~10 months later. All participants will be treated with an antimalarial medication prior to the third injection and prior to fourth injection. They will be followed for approximately 6 months after third and fourth injection. At vaccine visits, female participants will have a pregnancy test before injection. All participants will have an arm cleaned and the vaccine injected in a vein. They will be watched for 30 minutes. At non-vaccine visits, participants will have a physical exam and be asked how they are feeling. They will usually have blood tests.

Detailed description

It is known that humans can be protected against malaria by repeated immunization with radiation-attenuated sporozoites. Sanaria, Inc. has developed a process for manufacturing, in compliance with current Good Manufacturing Practices (cGMPs) aseptic, purified, radiation- attenuated cryopreserved sporozoites from a well-characterized isolate of Plasmodium falciparum (Pf). This product, which is called PfSPZ Vaccine, can be administered by needle and syringe. A collaboration among the Malaria Research and Training Center (MRTC, Mali), the Laboratory of Malaria Immunology and Vaccinology (LMIV) National Institute of Allergy and Infectious Diseases (NIAID), and Sanaria, Inc. has shown that sterile protection against naturally occurring malaria infection can be achieved. In this study, five doses of 2.7 x 10\^5 PfSPZ during the dry season resulted in protective efficacies of about 48% by time to first positive blood smears (BS) and about 29% by proportion of participants with at least one positive BS during a full malaria transmission season (20 weeks), higher than those reported for other malaria vaccine candidates. A follow up study in 2015 (ClinicalTrials.gov Identifier: NCT02627456) that reduced the number of vaccinations (from 5 to 3) while increasing the dose of sporozoites at each vaccination (2.7 x10\^5 to 1.8x10\^6 PfSPZ Vaccine) was conducted. Preliminary results show that 42 of 55 (77.8%) participants from the placebo group and 32 of 54 participants (58.1%) from the vaccine group developed Pf infection. Per protocol, the vaccine efficacy (VE) was 51% (p=0.004, 95% CI 20-70) by time-to-infection analysis (intention to treat (ITT) 39%, p=0.033) and 24% (p=0.031, 95% CI 2-41) by proportional analysis (ITT 22%, p= 0.041), similar to the previous study. Studies are ongoing to establish a vaccination regimen, optimum dose and schedule, that will lead to improved sterile protection in endemic regions. Preliminary results from more recent studies in malaria-naïve and malaria-experienced participants have shown that 9.0x10\^5 PfSPZ Vaccine dose per vaccination (lower than 1.8 x10\^6 used in studies above) in a three-dose regimen may be an optimal dose for immunization. In addition, there is emerging evidence that a condensed, more practical regimen may also lead to development of sterile immunity. This proposed study is therefore designed to assess safety, immunogenicity and protective efficacy of two separate three-dose vaccination regimens during natural transmission season. Participants in the main phase were randomized into arms receiving either PfSPZ Vaccine or normal saline injections. Each group received three doses of the respective injection during Year 1. After completion of the follow up in the main phase, all participants that are still enrolled in the study will be offered continued participation to receive a booster dose of the vaccine (dose # 4) with 9.0x10\^5 PfSPZ or normal saline (depending on the group they were originally randomized to) at approximately 10 months post #3 vaccination. The booster dose is timed prior to ensuing malaria transmission season. Participants will be followed, similarly to the follow up during the main phase, for safety and vaccine efficacy for approximately 6 months during this second transmission season.

Conditions

• Malaria

Interventions

Type	Name	Description
BIOLOGICAL	PfSPZ Vaccine	PfSPZ Vaccine is Radiation attenuated, aseptic, purified, vialed, cryopreserved, NF54 P. falciparum sporozoites produced by Sanaria, Inc.
DRUG	Normal Saline	Clear liquid indistinguishable from the study product will be used as a placebo rather than a comparator vaccine.
DRUG	artemether 20mg/lumefantrine 120mg (AL)	Licensed antimalarial in the US and Mali for use for uncomplicated malaria.

Timeline

• Start date: 2018-05-14
• Primary completion: 2019-11-23
• Completion: 2020-02-13
• First posted: 2018-04-27
• Last updated: 2021-08-20
• Results posted: 2021-08-20

Locations

1 site across 1 country: Mali

Regulatory

• FDA-regulated drug study