Phase 1/II, Safety and Immunogenicity Study of AERAS-404 in 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

• 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)
• Source documentation of birth weight ≥ 2.5 kg.
• Documented BCG vaccination within 72 hours of birth.
• Documented receipt of all age-appropriate EPI vaccines, except Rotavirus, for Cohorts 4 to 6 (see Appendix II).
• Source documentation of a negative HIV status in the mother, from any time during pregnancy with this child through randomization.
• Documentation of infant HIV negative exposure or infection status with negative HIV ELISA and HIV DNA PCR tests.
• Parent or legal guardian able and willing to provide signed informed consent.
• Participant/parent/legal guardian able to attend all scheduled visits and to comply with all trial procedures.

Exclusion criteria

• History of TB exposure in household or non-household contact.
• History/Evidence of TB disease or infection.
• Quantiferon positive.
• Prior TST test.
• Any one of Anemia, Neutropenia, Thrombocytopenia, SGPT (ALT), SGOT (AST) or Creatinine ≥ Grade 2
• Receipt of a live vaccine within 28 days prior to randomization.
• Receipt or planned receipt of any investigational vaccine.
• Known or suspected congenital immunodeficiency.
• Receipt of immunosuppressive therapy or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
• Known or suspected autoimmune disease
• 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.
• Participation in another clinical trial for an investigational product (IP).
• Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding randomization, contraindicating IM vaccination.
• Chronic illness that, in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion.
• 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.

• Systemic antibiotic use within 48 hours prior to randomization.