Study of AERAS-402 in Healthy Infants

• Adverse Events collected per subject [ Time Frame: 6 to 24 months post vaccination ] [ Designated as safety issue: Yes ]
  AEs are recorded for 28 days post vaccination SAEs are recorded for the entire study period to assess the safety profile
• Number of cases of TB are collected in the subjects entered in the study [ Time Frame: 24 months post vaccination ] [ Designated as safety issue: No ]
  To evaluate the efficacy of AERAS-402 in the prevention of TB in infants based on TB case definition endpoint #1 as described in the protocol.

• Percentage of cells expressing various cytokines will be measured in all subjects [ Time Frame: 24 months post vaccination ] [ Designated as safety issue: No ]
  To evaluate the immunogenicity of AERAS-402 compared to controls, flow cytometric intracellular cytokine staining (ICS) of CD4 and CD8 T cells producing one, two or three cytokines (IFN-γ, TNF-α, and/or IL-2) simultaneously after stimulation with a peptide pool of mycobacterial peptides.
• Number of subjects that have positive QuantiFERON tests after vaccination [ Time Frame: 24 months post vaccination ] [ Designated as safety issue: No ]
  To evaluate the proportion of on-study QuantiFERON conversions in infants that received AERAS-402 compared to controls.
• Number of subjects with probable TB [ Time Frame: 24 months post vaccination ] [ Designated as safety issue: No ]
  To evaluate the efficacy of AERAS-402 in the prevention of TB in infants based on TB case definition endpoints #2 and #3 as specified in the protocol.

AERAS-402 will be given to infants of at least 16 weeks of age who have already been vaccinated with BCG to determine if AERAS-402 will increase protection of infants to tuberculosis.

The only currently available tuberculosis vaccine, bacillus Calmette-Guérin (BCG), is estimated to reduce the risk of tuberculosis (TB) in children by up to 70-80%, but protection is incomplete. Efforts to increase TB protection in children include new vaccines for primary immunizations as well as combinations of vaccines given as primary and boosting vaccinations. AERAS 402 presents Mycobacterium tuberculosis (Mtb) antigens in the setting of a new, live, replication-deficient adenovirus vaccine that may increase T cell-mediated immunity and thus protection from tuberculosis. AERAS-402 appears safe and immunogenic in adults. Since BCG-vaccinated infants are the population for which AERAS-402 might be indicated, AERAS-402 will be administered to infants of at least 16 weeks of age who have already been vaccinated with BCG. This is the first Phase II study of AERAS-402 in infants.

• Experimental: Group One - Dose Finding - Low Dose
  Subjects enrolled in Study Group 1 will be randomized in a ratio of 3:1 to receive two doses of AERAS-402 at the lowest dose level or placebo, once on Study Day 0 and again on Study Day 28.
  Intervention: Biological: AERAS-402
• Experimental: Group 2 - Dose Finding - Middle dose -
  Subjects enrolled in Study Group 2 will be randomized in a ratio of 3:1 to receive two doses of AERAS-402 at the middle dose level or placebo, once on Study Day 0 and again on Study Day 28.
  Intervention: Biological: AERAS-402
• Experimental: Group 3 - Dose Finding - High Dose
  Subjects enrolled in Study Group 3 will be randomized in a ratio of 3:1 to receive two doses of AERAS-402 at the highest dose level or placebo, once on Study Day 0 and again on Study Day 28.
  Intervention: Biological: AERAS-402
• Experimental: Group 5 - Safety Cohort
  Subjects will receive three doses of AERAS-402 at the selected dose level or placebo, once on Study Day 0, again on Study Day 28, and again on Study Day 280.
  Intervention: Biological: AERAS-402
• Experimental: Group 4 - Dose Finding Group 2
  These additional 96 subjects will be randomized (1:1:1:1) in a parallel design to receive two doses of either AERAS-402 (1.5 x 1010, 3.0 x 1010, or 1.0 x 1011 vp) or placebo, once on Study Day 0 and again on Study Day 28.
  Intervention: Biological: AERAS-402

Inclusion Criteria:

1. Parent/legal guardian has completed the written informed consent process
2. Is age greater than or equal to 112 days (16 weeks) and less than or equal 182 days (26 weeks) on Study Day 0
3. Has general good health, confirmed by medical history and physical examination
4. Is up to date on all EPI immunizations for his/her age with a minimum of 14 days between the last EPI vaccination and administration of study vaccine on Study Day 0
5. Has ability to complete follow-up period of 728 days as required by the protocol
6. Parent/legal guardian is able and willing to stay in contact with the study site for the duration of the study and to provide updated contact information as necessary, and has no current plans to move from the study area for the duration of the study
7. Has completed simultaneous enrollment in Aeras Vaccine Development Registry protocol
8. Had BCG vaccination ≥ 3 months prior to randomization documented by medical card

Exclusion Criteria:

1. Acute illness, evidence of any significant active infection or temperature >=37.5°C on the day of randomization
2. Used immunosuppressive medication within 45 days before entry into the study (inhaled and topical corticosteroids are permitted)
3. Received immunoglobulin or blood products within 45 days before entry into the study
4. Ever received any investigational drug therapy or investigational vaccine
5. History or laboratory evidence of individual immunodeficiency virus (HIV-1) infection
6. History of allergic disease or reactions to any component of the study vaccine
7. Previous medical history that may compromise the safety of the participant in the study
8. Evidence of a new acute illness that may compromise the safety of the participant in the study
9. Inability to discontinue daily medications during the study
10. History or evidence of any systemic disease on physical examination or any acute or chronic illness that may interfere with the evaluation of the safety or immunogenicity of the vaccine, e.g., including masses between the leg and abdomen (e.g., inguinal hernia or lymphadenopathy)
11. History or evidence of active tuberculosis
12. A positive QuantiFERON®-TB Gold In-Tube test
13. A household contact with active TB disease