Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study of AERAS-404 Tuberculosis (TB) vaccine administered intramuscularly in Bacille Calmette-Guerin (BCG) primed infants.

This is a Phase I/II, randomized, double-blind, placebo-controlled, safety, immunogenicity and dose-range finding study in HIV-uninfected, HIV-unexposed, BCG-primed infants. The study vaccine AERAS-404 or placebo will be administered without concomitant EPI vaccines (Cohorts 1 to 5, N = 159 subjects) and with concomitant EPI vaccines (Cohort 6, N = 70 subjects). Study vaccine or placebo will be administered as a single dose (injection) at Study Day 0 ( ≥168 to ≤ 196 days of age, Cohorts 1 and 2), a 2-dose schedule at Study Day 0 (≥ 168 to ≤ 189 days of age) and Study Day 28 (Cohorts 3A and 3B) or a 3-dose schedule at Study Day 0 (≥ 84 to ≤ 98 days of age), Study Day 42 and Study Day 98 (Cohorts 4 and 5). Subjects in Cohort 6 will receive the study vaccine or placebo at Study Day 0 (≥ 64 to ≤ 83 days of age), Study Day 28 (≥ 91 to ≤ 105 days of age), and Study Day 210 (≥ 273 to ≤ 287 days of age). A cohort will enroll once safety in the previous cohort has been established. AERAS-404 is an investigational vaccine manufactured by Sanofi Pasteur (SP) and Statens Serum Institute (SSI).

INCLUSION CRITERIA

1. Age at time of entry:

   Cohorts 1 to 6

   • Cohorts 1 and 2: ≥ 168 to ≤ 196 days
   • Cohorts 3A and 3B: ≥ 168 to ≤ 189 days
   • Cohorts 4 and 5: ≥ 84 to ≤ 98 days (≥ 2 weeks after receipt of EPI vaccine doses at 10 weeks of age)
   • Cohort 6 - coincident with EPI vaccine doses at 10 weeks of age (≥ 64 to ≤ 83 days of age)

2. Source documentation of birth weight ≥ 2.5 kg.

3. Documented BCG vaccination within 72 hours of birth.

4. Documented receipt of all age-appropriate EPI vaccines, except Rotavirus, for Cohorts 4 to 6 (see Appendix II).

5. Source documentation of a negative HIV status in the mother, from any time during pregnancy with this child through randomization.

6. Documentation of infant HIV negative exposure or infection status with negative HIV ELISA and HIV DNA PCR tests.

7. Parent or legal guardian able and willing to provide signed informed consent.

8. Participant/parent/legal guardian able to attend all scheduled visits and to comply with all trial procedures.

EXCLUSION CRITERIA

1. History of TB exposure in household or non-household contact.

2. History/Evidence of TB disease or infection.

3. Quantiferon positive.

4. Prior TST test.

5. Any one of Anemia, Neutropenia, Thrombocytopenia, SGPT (ALT), SGOT (AST) or Creatinine ≥ Grade 2

6. Receipt of a live vaccine within 28 days prior to randomization.

7. Receipt or planned receipt of any investigational vaccine.

8. Known or suspected congenital immunodeficiency.

9. Receipt of immunosuppressive therapy or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

10. Known or suspected autoimmune disease

11. Hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to a vaccine containing any of the same substances as the vaccine used in the trial.

12. Participation in another clinical trial for an investigational product (IP).

13. Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding randomization, contraindicating IM vaccination.

14. Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.

15. Febrile illness (temperature ≥ 100.4°F [≥ 38.0°C]) within 24 hours prior to randomization.

    Note: A subject may enroll after recovery from febrile illness if the subject is still within the age window.

16. Systemic antibiotic use within 48 hours prior to randomization.