This is a first-in-humans safety, immunogenicity and efficacy study with recombinant protein VMP001, a Plasmodium vivax circumsporozoite (CS) protein based vaccine. This open label study will be performed in malaria-naïve adults in the United States. Three doses of VMP001 formulated in AS01B (adjuvant system) will be given intramuscularly at different intervals followed by a challenge with P. vivax infected mosquitoes. Safety, immunogenicity and efficacy parameters will be studied.
This is a Phase 1/2a, non-randomized, open label, dose escalation study in healthy, malaria-naïve adults aged 18 to 55 years (inclusive). The vaccine will be administered with GlaxoSmithKline Biologicals' adjuvant system AS01B. This is a first-in-human study of VMP001; therefore the study design will incorporate a dose-escalation phase evaluating 15 µg, 30 µg, and 60 µg doses of VMP001 in 500 µL of AS01B. A total of 30 volunteers, divided into 3 groups (10 in each group), will receive 3 doses of the VMP001/AS01B vaccine. Group 1 will receive 15 µg of VMP001, Group 2 will receive 30 µg of VMP001, and Group 3 will receive 60 µg of VMP001 at each immunization. The dose of AS01B will be 500 µL for all groups. The first and second dose in each group will be separated by 28 days. The third dose in the three groups will be given at intervals scheduled to normalize the time to challenge between the last immunization and challenge. The second and third dose in Group 1 will be separated by 56 days, Group 2 by 42 days and Group 3 by 28 days. The challenge will occur 2 weeks following the third immunization. A group of 6-12 infectivity controls will begin participation in the study at the challenge stage. They will not receive any immunizations or placebos prior to challenge. All volunteers will receive a standard treatment regimen consisting of chloroquine and primaquine on the day that parasitemia is detected. Volunteers who do not become parasitemic will also begin the same treatment regimen on day 28 following the challenge (study day 126). \> \> Safety and immunogenicity will be evaluated during the study through the final study visit 6 months after challenge (study day 280).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Plasmodium vivax malaria protein 001 (VMP001) with GSK Biologicals' Adjuvant System AS01B
P. vivax sporozoite challenge
Clinical Trials Center, Walter Reed Army Institute of Reserach
Silver Spring, Maryland, United States
Occurrence of Solicited Adverse Events Over a 7 Day Follow-up Period After Each Immunization (the Day of the Immunization and 6 Subsequent Days) During the Vaccination Phase
Adverse events were evaluated for 7 days after each vaccination during the vaccine phase.
Time frame: 7 days after immunization
Occurrence of Unsolicited Adverse Events Over a 28 Day Follow-up Period After Each Immunization (the Day of the Immunization and 27 Subsequent Days) During the Vaccination Phase
Adverse events were evaluated over a 28 day follow-up period after each vaccination during the vaccine phase
Time frame: 28 days following immunization
Occurrence of Serious Adverse Events at Any Time During the Study Period (Enrollment to Final Follow up Visit)
Occurrence of serious adverse events at any time during the approximately 463 day study period
Time frame: up to 463 days
Time to Parasitemia for Immunogenicity Population
Subjects were ranked according to time of onset of parasitemia and a non-parametric rankorder statistical test (eg, Log-Rank or Mann-Whitney) was performed to evaluate delays in parasitemia induced by vaccination. Cox Proportional Hazards model was used to calculate days to parasitemia and Kaplan-Meier plots were used to display time to first positive malaria blood smear. Hazard Ratio (HR). Time starts once subject has received t infectious bites. Time stops when subject has first positive blood smear. If subject does not become parasitemic then time stops the day he/she begins anti-malarial therapy.
Time frame: 280 day (during the study through 6 months aftr challenge)
Geometric Mean of Anti-VMP001 Antibody Titers in Serum Per Immunogenicity Population
Anti-VMP001 antibody concentrations were measured and summarized by geometric mean titers (GMT) with 95% confidence interval (CI). Peak responses were compared by performing Student's t-test on data normalized by log transformation to ascertain the presence or absence of significant dose response differences. ELISA Units (EU) were converted to log10 values for calculations and statistical comparison of geometric means. Units that were reported as '\>50' were converted to '1'.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Masking
NONE
Enrollment
41
Time frame: study duration
Geometric Mean of Anti-VMP001 Anti-body Titers in Serum Per Efficacy Population
Anti-VMP001 antibody concentrations were measured and summarized by geometric mean titers (GMT) with 95% confidence interval (CI). Peak responses were compared by performing Student's t-test on data normalized by log transformation to ascertain the presence or absence of significant dose response differences. ELISA Units (EU) were converted to log10 values for calculations and statistical comparison of geometric means. Units that were reported as '\>50' were converted to '1'.
Time frame: study duration