This is a phase I randomized, double blind clinical trial designed to evaluate the safety, tolerability and immunogenicity of the ID93 recombinant protein antigen alone or formulated with GLA-SE or AP10-602 adjuvant in 70 healthy adults 18-49 years of age. Subjects will receive a total of 3 doses administered intramuscularly on Days 1, 29 and 57. Subjects will be monitored for approximately 422 days (365 days following the third study injection), including safety laboratory analyses done just prior to and 7 days following each study injection. Blood samples will be obtained for immunological assays (Luminex, intracellular cytokine staining at Days 1 and 71, and antibody analysis at Days 1 and 85). The primary objective is to evaluate the safety and tolerability of 10 µg ID93 + 5 or 10 µg AP10-602 compared to 10 µg ID93 + 5 µg GLA-SE and 10 µg ID93 alone following three consecutive intramuscular injections administered on Days 1, 29 and 57.
TB causes significant morbidity and mortality throughout the world. Strains of Mtb are becoming increasingly resistant to antimycobacterial drugs and therapy is often associated with poor compliance, which increases the likelihood of antimicrobial resistance. The current licensed BCG vaccine does not prevent reactivation or reinfection in adults so there is a great need for a more effective vaccine. ID93 is a recombinant antigen that, when mixed with the adjuvants GLA-SE and AP10-602, shows great promise in eliciting what is thought to be an important Th1 T cell response and limits the bacterial burden in Mtb challenged animals. This study is a phase I randomized, double blind clinical trial designed to evaluate the safety, tolerability and immunogenicity of the ID93 recombinant protein antigen alone or formulated with GLA-SE or AP10-602. This study will enroll 70 healthy males and non-pregnant females subjects, aged 18 to 49. Subjects who meet all eligibility criteria will be randomized to ID93 alone, ID93 + GLA-SE, or ID93 + AP10-602 at either dose level. Study injections will be performed and subjects will be observed in clinic for 30 minutes. All subjects will complete a written subject memory aid that solicits local and systemic reactogenicity adverse events for 7 days following each study injection. After subjects are reevaluated to ensure they continue to meet eligibility criteria they will undergo second and third study injections on Days 29 and 57. General safety will be evaluated on Days 1, 3, 8, 29, 31, 36, 57, 59, 64, 71, 85, 169, and 422 for each subject. The occurrence of serious adverse events and the new onset of any adverse events of special interest (AESI) will be collected throughout the study period (approximately 422 days). Each subject's duration of participation will be about 15 months. The Primary Objective is : To evaluate the safety and tolerability of 10 µg ID93 + 5 or 10 µg AP10-602 compared to 10 µg ID93 + 5 µg GLA-SE and 10 µg ID93 alone following three consecutive intramuscular injections administered on Days 1, 29 and 57. The Secondary Objective is: To assess the immunogenicity of 10 µg ID93 + 5 or 10 µg AP10-602 compared to 10 µg ID93 + 5 µg GLA-SE and 10 µg ID93 alone by quantifying T cell responses and IgG antibody responses to ID93 at specified time points.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
DOUBLE
Enrollment
70
AP10-602 contains GLA formulated with liposomes and an additional immunological adjuvant. The ID93 (10 mcg) + AP10-602 (5 mcg) arm will receive intervention on days 1, 29 and 57. The ID93 (10 mcg) + AP10-602 (10 mcg) arm will receive intervention on days 1, 29 and 57.
Glucopyranosyl Lipid A- Stable oil-in-water emulsion (GLA-SE). The ID93 (10 mcg) + GLA-SE (5 mcg) arm will receive intervention on days 1, 29 and 57
ID93 is a fusion polyprotein comprising four Mtb antigens (Rv2608, Rv3619, Rv3620, Rv1813). All arms will receive 10 mcg ID93 IM on days 1, 29 and 57
University of Iowa - Vaccine Research and Education Unit
Iowa City, Iowa, United States
The number of serious adverse events considered related to the study injection reported at any point during the study period.
Time frame: Day 1 through Day 422
The number of subjects experiencing solicited injection site reactions within 7 days following study injection.
Time frame: 7 days following each study injection
The number of subjects experiencing solicited systemic reactions within 7 days following study injection.
Time frame: 7 days following each study injection
The number of subjects spontaneously reporting adverse events considered related to the study injection at any point during the study period.
Time frame: Day 1 through Day 422
Mean fold change from baseline (Day 1) in IgG antibody responses to ID93 on Day 85.
Time frame: Day 1 and Day 85
Percentage of CD4 and CD8 T cells producing 1 or more cytokines (IFN-gamma, TNF and IL-2) simultaneously in response to stimulation with the ID93 antigen as measured by intracellular cytokine staining at Day 71 relative to baseline (Day 1).
Time frame: Day 1 and Day 71
The magnitude of Th1 and Th2 cytokine production in PBMCs in response to the ID93 antigen relative to baseline (Day 1) at Day 71, as assayed by Luminex.
Time frame: Day 1 and Day 71
The proportion of subjects with at least a 4-fold increase in IgG antibody responses to ID93 on Day 85 relative to baseline (Day 1).
Time frame: Day 1 through Day 85
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