This is a first-in-human phase I, open-label, single-site, dose escalation study to determine the safety, tolerability and Plasmodium falciparum transmission reducing activity of the R0.6C vaccine in two different adjuvant combinations.
Thirty-two healthy adult volunteers will be recruited and divided over the study arms that will receive four vaccinations on days 0, 28, 56 and 168 with either 30μg or 100μg of R0.6C adjuvanted with Alhydrogel alone, or combined with Matrix-M1. Three volunteers (Group 1A, n=3) will receive four vaccinations with the lower dose of 30μg R0.6C with Alhydrogel, and, in parallel, three volunteers (Group 1B, n=3) will receive four vaccinations with the lower dose of 30μg R0.6C with Alhydrogel and Matrix-M1. Volunteers will be closely monitored for adverse events for a period of minimally 14 days after the first vaccination. If safe, an additional 5 volunteers per adjuvant arm (groups 2A and 2B) will then receive four vaccinations with the lower dose (30μg R0.6C). If considered safe following a minimum of 14 days of follow-up after the first R0.6C administration of groups 2A and 2B, three volunteers per adjuvant arm (groups 3A and 3B) will start the vaccination regimen with the higher dose of 100μg R0.6C. Finally, a minimum of 14 days after administration of the first vaccination in groups 3A and 3B, if considered safe, an additional 5 volunteers per adjuvant arm (groups 4A and 4B) will initiate the vaccination regimen with the higher dose of 100μg R0.6C. There will be no placebo group. All volunteers will be followed up for adverse events until 84 days after the last immunisation. Total trial duration is approximately 8 months for each subject. Blood will be collected to assess functional Plasmodium falciparum transmission reducing activity (TRA) and transmission blocking activity (TBA) by standard membrane feeding assay (SMFA), as well as immunogenicity, at pre-specified time points after R0.6C vaccinations compared to pre-vaccination values.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
32
Vaccination with R0.6C transmission blocking vaccine. Volunteers will sequentially receive four administrations of R0.6C intramuscularly in the deltoid muscle on alternating sides on days 0, 28, 56 and 168.
Radboud university medical center
Nijmegen, Gelderland, Netherlands
Number of Serious Adverse Events and Grade 3 Adverse Events
The number of serious adverse events and solicited and unsolicited grade 3 adverse events possibly, probably or definitely related to the vaccine in the period from first R0.6C administration up to 84 days after the last immunization.
Time frame: From first immunization up to 84 days after the last immunization
Transmission Reducing Activity
The functional transmission reducing activity in the standard membrane feeding assay of volunteer sera collected two weeks after the fourth R0.6C immunization (I4+14), compared to baseline (I1-1) within each of the four dose-adjuvant groups. The TRA was calculated by dividing the total number of oocysts in mosquitoes fed with I4+14 sera by total number of oocysts in mosquitoes fed with I1-1 sera.
Time frame: 14 days after the fourth immunization
Number of Grade 1 and 2 Adverse Events
The number of solicited and unsolicited grade 1 and 2 adverse events possibly, probably or definitely related to the vaccine in the period from first R0.6C administration up to 84 days after the last immunization.
Time frame: From first immunization up to 84 days after the last immunization
Transmission Reducing Activity
The transmission reducing activity at other timepoint (I1+14, I2+14, I3+14, I3+111 \[I4-1\], and I4+84) compared to baseline (I1-1) in each of the four dose-adjuvant groups. The TRA was calculated by dividing the total number of oocysts in mosquitoes fed with I1+14, I2+14, I3+14, I3+111 \[I4-1\], and I4+84 sera by total number of oocysts in mosquitoes fed with I1-1 sera.
Time frame: 14 days after immunization 1, 2 and 3. One day before immunization 4 and 84 days after immunization 4.
Anti-6C Antibody Quantities
The anti-6C antibody quantity in volunteer sera collected two weeks after fourth R0.6C immunization (I4+14) and at other time points (I1+14, I2+14, I3+14, I3+111 \[I4-1\], and I4+84) compared to baseline (I1-1) in each of the four dose-adjuvant combinations, as determined by ELISA.
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Time frame: 14 days after each immunization. One day before immunization 4 and 84 days after immunization 4.