This is a Phase I, open-label, dose-escalation study with three study groups. This study will be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection (LTBI) and 8 of whom will not have LTBI at study enrollment. The investigational product is AERAS-456 at a dose of 15 ug of H56 antigen with IC31 500 nmol KLK (15/500), and a dose of 50 ug of H56 antigen with IC31 500 nmol KLK (50/500). The vaccine is administered by intramuscular injection.
This is a Phase I, open-label, dose-escalation study with three study groups. This study will be conducted in 25 HIV negative subjects, 17 of whom will have Latent Tuberculosis Infection (LTBI) and 8 of whom will not have LTBI at study enrollment. The investigational product is H56:IC31 (AERAS-456) at a dose of 15 ug of H56 antigen with IC31 500 nmol KLK (15/500), and a dose of 50 ug of H56 antigen with IC31 500 nmol KLK (50/500). The vaccine is administered by intramuscular (IM) injection. Subjects will be assigned to a study group based on LTBI status at enrollment and time of completion of screening. Subjects without LTBI will be assigned to Group 1. Subjects with LTBI will be sequentially assigned to Groups 2 and 3 based on the order in which they complete screening. All subjects will receive a first dose of study vaccine on Study Day 0, a second dose of study vaccine on Study Day 56, and a third dose of study vaccine on Study Day 112. Enrollment of subjects into Group 2 will begin only after a review of safety data from the 14-day period after initial vaccination of all subjects in Group 1. Likewise, enrollment of subjects into Group 3 will begin only after the corresponding review of safety data from Group 2. The total duration of study follow-up for all subjects is 210 days. Study groups 1-2 will enroll 8 subjects each and study group 3 will enroll 9 subjects. This study is planned at a single clinical site in South Africa. The sizes specified for each study group were selected because they are judged to be adequate for preliminary safety and immunogenicity evaluations for a Phase I study rather than for statistical reasons.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
25
H56:IC31 contains a fusion protein (referred to as H56 antigen, or H56) of 3 mycobacterial antigens (the early secreted antigens Ag85B and ESAT-6, and the latency antigen Rv2660c) formulated in the Th1-stimulating IC31 adjuvant.
SATVI Project Office, Brewelskloof Hospital
Worcester, South Africa
Number of Participants With at Least One Adverse Event (AE) Through Day 210
Solicited AEs: through 14 days after each vaccination Unsolicited AEs: post-vaccination on Study Days 0, 56, and 112 through 28 days after vaccination Injection site reactions and axillary lymphadenopathy: post-injection on the day of each vaccination, and Study Days 2 , 7, 14, and 28 days after each vaccination Serious adverse events (SAE): through Study Day 210
Time frame: Through Study Day 210
Median % Change in Response to Peptides From Vaccine Antigen Ag85B From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations
Whole blood ICS Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response Antigen: Ag85B Cytokine(s): G+2+17+T+ %CD4+ T Cell Response
Time frame: Study Day 70
Median % Change in Response to Peptides From Vaccine Antigen ESAT-6 From Pre-vaccination to Day 70 in Participants Who Received Two Vaccinations
Percent Antigen-Specific T Cell UNS-subtracted Cytokine Response 12-Hour Whole Blood Intracellular Cytokine Staining (ICS) Assay Antigen: ESAT6 Cytokine(s): G+2+17+T+ %CD4+ T Cell Response
Time frame: Study Day 70
Number of Participants Who Received at Least Two Vaccinations and Tested Positive for Mtb Infection on Day 210
Measure of Mtb positivity by QuantiFERON-TB Gold In-Tube Number of Positive Responses and Shift from Screening to Study Day 210 Post-Vaccination Responses
Time frame: Study Day 210
Median % Change in Response to Peptides From Vaccine Antigen Ag85AB From Pre-vacc to Day 210
Responses to vaccine antigen Ag85B measure by Interferon gamma (IFN-γ) ELISpot assay Unstimulated-subtracted IFN-γ ELISpot Response (Spot forming units/10\^6 PBMC) Antigen: Ag85B
Time frame: Study Day 210
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.