NCT05468606

Coadministration of GA2 Sporozoites With Adjuvants

Coadministration of Genetically Attenuated Plasmodium Falciparum ∆mei2 (GA2) Sporozoites With Adjuvants - a Proof of Principle Study

• Status: Unknown
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 45 (estimated)
• Sponsor: Leiden University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

This study will assess the coadministration of genetically attenuated Plasmodium falciparum ∆mei2 (GA2) sporozoites with adjuvants (BCG and YF-17D vaccination and imiquimod cream). Primary outcomes will be safety, tolerability and protective efficacy against CHMI.

Detailed description

This will be an adaptive design single center, randomized controlled partly blinded, partly open-label clinical proof-of-principle trial of the genetically attenuated parasite GA2 co-administered with adjuvants in healthy, malaria-naïve male and female participants with no prior history of BCG or YF-17D vaccination. A total of 45 participants will be immunized by the bites of 50 GA2 infected mosquitos. Additionally, ten participants will serve as infectivity controls and will be exposed to the bites of 50 uninfected mosquitoes in the immunization phase. During the 42 days following the immunization, there will be four out-patient visits and one phone call visit to evaluate adverse events and for hematology, biochemistry and immunology laboratory assessment. Six weeks after immunization, all 45 participants will undergo a CHMI through the bites of 5 mosquitos infected with wild-type 3D7 sporozoites. From day 6 to 21 after CHMI, participants will be followed daily on an out-patient basis to determine parasite loads detected by a quantitative polymerase chain reaction (qPCR). As soon as parasitemia is detected (cut-off \>100p/mL), or at the latest 28 days after CHMI, participants will be treated with a curative regimen of antimalarials. The trial will be held in two cohorts: the second cohort starting 4 weeks after the first. The first cohort will consist of 10 participants and the second cohort will consist of 15 participants. Both cohorts will be block randomized to the five different study groups. The study will consist of three stages. In stage A of the study, ten GA2 immunized participants will be compared to five infectivity controls in a blinded design. If the protective efficacy of the GA2 immunized group is ≤7/10 and some efficacy is seen in stage A (either ≥10% protection or significant increase in time to parasitemia) then the study will progress to stage B. In this stage, BCG (n=5), YF-17D (n=5) or imiquimod (n=5) will be applied/administered to the GA2 administration site. Additionally, two infectivity controls will participate in stage B. Stage B will be open label. Based on the data on safety, tolerability and immunogenicity, the most favorable adjuvant of stage B can be chosen to be further assessed in stage C. In stage C, additional participants will be immunized with 50 GA2 infected mosquitoes in combination with the selected adjuvant. Additionally, a group of five unadjuvanted GA2 immunized participants and three infectivity controls will participate. The adjuvanted group of stage C will be open-label, the unadjuvanted group and the infectivity controls will be blinded.

Conditions

• Malaria,Falciparum

Interventions

Type	Name	Description
BIOLOGICAL	GA2	GA2 sporozoites administered by 50 mosquito bites
BIOLOGICAL	BCG	0.1 mL BCG vaccine intradermally
BIOLOGICAL	YF-17D (fractional ID dose)	0.1 mL YF17D vaccine intradermally
DRUG	Imiquimod	250mg imiquimod 5% cream topical
OTHER	Mock immunization	50 bites by uninfected mosquitoes

Timeline

• Start date: 2023-02-03
• Primary completion: 2024-12-01
• Completion: 2024-12-01
• First posted: 2022-07-21
• Last updated: 2023-02-10

Locations

1 site across 1 country: Netherlands