Latent Tuberculosis Clinical Trial
Official title:
A Phase I/IIa Double-Blind, Randomized, Placebo-controlled Dose-Finding Study to Evaluate the Safety and Immunogenicity of AERAS-456 in HIV-Negative Adults With and Without Latent Tuberculosis Infection
This is a Phase I/IIa, double-blind, randomized, placebo-controlled, dose- and regimen-finding study in healthy adults with and without LTBI, who are BCG-vaccinated, HIV negative, and have no history or evidence of TB disease. The investigational product is AERAS-456 at 3 dose levels: 5, 15, and 50ug of H56 antigen with 500 nmol IC31. The vaccine is administered by IM injection.
This is a Phase I/IIa, double-blind, randomized, placebo-controlled, dose- and
regimen-finding study in healthy adults with and without latent Tuberculosis (TB) Infection,
who are Bacille Calmette Guerin (BCG)-vaccinated, HIV negative, and have no history or
evidence of TB disease. The investigational product is AERAS-456 at 3 dose levels: 5, 15, and
50ug of H56 antigen with 500 nmol IC31. The vaccine is administered by intramuscular (IM)
injection. The study will be conducted at two sites in South Africa.
A total of 98 subjects will be enrolled in 2 phases into 4 groups based on Latent TB
Infection (LTBI) status. The initial phase will be a dose ranging study of a 2-dose regimen
at 3 dosage levels in LTBI(-) subjects, to select a dosage for the second phase. In the
second phase, the study will be expanded to evaluate both 2-dose and 3-dose regimens and to
include LTBI(+) subjects. In the first phase, 50 LTBI(-) subjects will be enrolled in Group 1
and randomized at a ratio of 3:3:3:1 to receive 2 doses of 5/500, 15/500, or 50/500 of
AERAS-456, or placebo given at Study Days 0 and 56 (Table 0 1).
One dose level of AERAS-456 will be selected by the sponsor and SSI for the second phase of
the study, based on analysis of unblinded safety and immunogenicity data through 28 days
after the second dose in the first phase, in conjunction with safety and immunogenicity data
from study C-032-456. The criteria for dose-selection will be specified in a statistical
analysis plan to be finalized prior to the unblinded review. The selected dose, in
conjunction with the unblinded safety and immunogenicity data, will be submitted to the SMC
for review. In the second phase, 48 subjects will be enrolled concurrently into Group 2
(LTBI[-]) and into Groups 3 and 4 (LTBI[+], Table 0 2). In each of Groups 2 and 4, 16
subjects will be randomized at a ratio of 3:1 to receive 3 doses of AERAS-456 or placebo
given at Study Days 0, 56, and 112. In Group 3, 16 subjects will be randomized at a ratio of
3:1 to receive 2 doses of AERAS-456 or placebo given at Study Days 0 and 56.
All subjects will stay on the study for 292 days after receiving the first vaccination. The
subjects in Groups 1 and 3 will be followed up for 236 days after the second vaccination and
subjects in Groups 2 and 4 will be followed up for 180 days after the third vaccination. The
sample size for each study cohort was selected because it was judged to be adequate for
preliminary safety and immunogenicity evaluations for a Phase I/IIa study rather than for
statistical reasons. Given 12 and 15 subjects in individual AERAS-456 dosing groups, the
study will have an 80% probability of detecting at least 1 specified event which occurs at a
rate of 12.5% and 10.0%, respectively. If no such events are observed among 12 and 15
subjects receiving active study vaccine, an approximation to the upper one-sided 95%
confidence bound on the rate of occurrence for that event would be 22% and 18%, respectively.
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