Safety, Tolerability, and Immunogenicity of the Vaccine Candidates ID93 + AP10-602 and ID93 + GLA-SE Administered Intramuscularly in Healthy Adult Subjects

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.

Inclusion Criteria:

1. Males and nonpregnant females between the ages of 18 and 49 years, inclusive. 2. Women
of childbearing potential* must agree to practice adequate contraception** for the 28-day
period before Day 0 through 90 days after the third study injection. * A woman is
considered of childbearing potential unless surgically sterile (tubal ligation, bilateral
oophorectomy, or hysterectomy) or post-menopausal (>/=1 year). **Acceptable birth control
methods include but are not limited to: abstinence from sexual intercourse with men;
monogamous relationship with a vasectomized partner; barrier methods (condoms, diaphragms,
spermicides, and intrauterine devices); and licensed hormonal methods. 3. In good health,
as judged by the investigator and determined by vital signs*, medical history, and a
targeted physical examination. * Temperature <38°C, heart rate 54 bpm,
systolic blood pressure 89 mmHg, diastolic blood pressure >/=60 mmHg. NOTE: Athletically trained subjects with a pulse >/=45 may be enrolled at the
discretion of the principal investigator or designated licensed clinical investigator. 4.
Screening laboratory values must be within site normal limits, though trace urine protein
is acceptable. -Blood hemoglobin -White blood cell (WBC) count -Neutrophil count -Platelets
-Creatinine -AST -ALT -Bilirubin (total) -Glucose (random, must be less than 140) -Urine
dipstick for protein and glucose (negative to trace protein are acceptable) -Negative
Quantiferon-TB Gold test -Negative HIV 1/2 antibody, (HBsAg), and Hepatitis C virus (HCV)
antibody NOTE: See Appendix D for site normal values. Creatinine values lower than the
normal range may be acceptable if the PI or a designated licensed clinician determines that
these laboratory findings are not clinically significant. HIV and hepatitis C viral load
PCR testing may be performed for individuals suspected of having indeterminate antibody
testing. For African American participants, a WBC of >/= 3.5 k/mm^3 is acceptable. 5. Able
to understand and comply with planned study procedures and willing to be available for all
study-required procedures, visits and calls for the duration of the study. 6. Provide
written informed consent before initiation of any study procedures. 7. Willing to abstain
from donating whole blood or blood derivatives until 90 days after the final study
injection.

Exclusion Criteria:

1. History of treatment for active or latent tuberculosis infection or history of positive
PPD. 2. History or evidence of active tuberculosis. 3. Has received vaccination or
immunotherapy with a BCG product at any time prior to randomization. 4. Shared a residence
within the last year prior to randomization with an individual on anti-tuberculosis
treatment or with culture or smear positive tuberculosis. 5. Received a tuberculin skin
test within 3 months (90 days) prior to the time of randomization through study day 85. 6.
Body temperature >/=100.4°F (>/=38°C) or acute illness within 3 days before study injection
days (subject may be rescheduled). 7. A positive serum* or urine pregnancy test at
screening or within 24 hours prior to study injection**, women who are planning to become
pregnant***, or women who are breastfeeding. * At screening visit only ** If female of
childbearing potential as defined in Inclusion Criterion #2 ***from 28 days prior to
entering the study until 90 days after the final study injection 8. Immunosuppression as a
result of an underlying illness or treatment or use of anticancer chemotherapy or radiation
therapy (cytotoxic) within the preceding 36 months. 9. An active neoplastic disease*
(excluding nonmelanoma skin cancer) or a history of any hematologic malignancy. * defined
as neoplastic disease or treatment for neoplastic disease within the past 5 years 10. A
history of autoimmune disease (systemic lupus, rheumatoid arthritis, scleroderma,
polyarteritis, thyroiditis, etc). 11. Used an immunosuppressive or immunomodulatory drug*
for 2 or more consecutive weeks within 6 months prior to the first study injection (nasal
and topical steroids are allowed). *such as >0.5 mg/kg/day or >/=20 mg total dose/day of
prednisone orally or >800 µg of inhaled beclomethasone 12. A diagnosis of schizophrenia,
bipolar disease, or history of hospitalization for a psychiatric condition or previous
suicide attempt. 13. A history of treatment for any other psychiatric disorder in the past
3 years that increases the risk to the subject in the opinion of the investigator. 14. A
history of receiving immunoglobulin or other blood product within 3 months prior to
enrollment through study day 85. 15. Received or plan to receive any live licensed vaccines
within 4 weeks or inactivated licensed vaccines within 2 weeks of any study injection. 16.
An acute or chronic medical condition that* would render study injections unsafe or would
interfere with the evaluation of responses or is not generally seen in healthy, normal
subjects. * in the opinion of the investigator NOTE: This includes, but is not limited to,
known cardiac disease, pulmonary disease, liver disease, renal disease, unstable or
progressive neurological disorders, diabetes mellitus, and transplant recipients. 17.
History of anaphylaxis or severe allergic reaction to vaccines or history of allergic
reaction to eggs, kanamycin-related antibiotics or other components in the antigen and
adjuvant formulations. 18. Receipt of an experimental agent* within 1 month before study
injections in this study or expectation to receive an experimental agent during the
15-month study period. * vaccine, drug, biologic, device, blood product, or medication 19.
Any condition that would* place the subject at an unacceptable injury risk, render him/her
unable to meet the requirements of the protocol, or that may interfere with successful
study completion. * in the opinion of the investigator 20. A history of alcohol or drug
abuse during the previous 1 year* or chronic marijuana abuse or any other illicit drug use.
* for example, daily excessive alcohol use or frequ ent binge drinking as determined by the
investigator 21. Presence of tattoos that would preclude evaluation of the injection site.