Evaluation of Safety, Immunogenicity, and Prevention of TB With AERAS-404 and BCG Revaccination in Healthy Adolescents
Condition: Tuberculosis
MeSH terms: Tuberculosis
Intervention: AERAS-404; Placebo; Bacillus Calmette-Guérin (BCG)
Intervention description: The H4 antigen is a fusion protein created from two Mtb antigens: antigen Ag85B and TB10.4. Ag85B is also referred to as α-antigen and is a 30-kDa mycolyl transferase protein. TB10.4 is one of three members of the very similar ESAT-6 group of proteins found in Mtb culture supernatants. TB10.4 induces broad immune responses in T cells isolated from TB subjects compared to BCG-vaccinated donors and unvaccinated donors. IC31 is a combination of a leucine-rich peptide named KLK & a synthetic oligonucleotide named ODN1a. The optimal molar ratio of KLK to ODN1a in mice is 25:1. AERAS-404 & saline placebo trial arms will be double-blinded since BCG causes a recognizable local injection site reaction, the BCG revaccination trial arm will be unblinded.; Saline; BCG SSI Vaccine is registered in South Africa for prevention of TB in children and adults. BCG, an attenuated, live culture of the Bacillus Calmette-Guérin, was originally attenuated between 1906 and 1919 by serial passage of an M. bovis strain. The manufacturer Statens Serum Institut (SSI) in Copenhagen, Denmark derives this vaccine from the Danish BCG strain 1331. BCG SSI is supplied by the manufacturer in amber 10-dose vials containing 0.75 mg lyophilized SSI BCG. The BCG revaccination trial arm will be unblinded (open label).
Intervention MeSH terms: BCG Vaccine
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 989.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: BCG Vaccinated

Summary:

      Randomized, Placebo Controlled, Partially Blinded Phase II Study to Evaluate Safety,
      Immunogenicity, and Prevention of Infection with Mycobacterium tuberculosis of AERAS-404 and
      BCG Revaccination in Healthy Adolescents
    

Eligibility criteria:

        Inclusion Criteria:

          1. Has completed the written informed consent and assent process

          2. Is age ≥ 12 years and ≤ 17 years on Study Day 0

          3. Agrees to stay in contact with the study site for the duration of the study, provide
             updated contact information

          4. For female subjects: agrees to avoid pregnancy from 28 days prior to Study Day 0 and
             for the full duration of the study.

          5. Has general good health, confirmed by medical history and physical examination

          6. Had BCG vaccination at least 5 years ago documented through medical history or by
             presence of healed BCG scar

          7. Tests QFT-GIT negative at screening, using the manufacturer's recommended threshold of
             0.35 IU/mL

        Exclusion Criteria:

          1. Acute illness on Study Day 0

          2. Oral temperature ≥37.5°C on Study Day 0

          3. Clinically significant (and no more than Grade 1 on the Toxicity Scale) abnormal
             laboratory values from blood collected within 21 days

          4. Evidence of clinically significant (and no more than Grade 1 on the Toxicity Scale)
             systemic or local disease on urinalysis

          5. History or evidence of any clinically significant systemic disease, or any acute or
             chronic illness that might affect the safety, immunogenicity, or efficacy of study
             vaccine in the opinion of the investigator

          6. History of treatment for active TB disease or latent Mtb infection

          7. History or evidence, including chest X-ray, of active TB disease

          8. Shared residence with an individual receiving anti-TB treatment, or known incompletely
             treated culture or smear positive TB

          9. History of autoimmune disease or immunosuppression

         10. Used immunosuppressive medication within 42 days before Study Day 0

         11. Received immunoglobulin or blood products within 42 days before Study Day 0

         12. Received any investigational drug therapy or investigational vaccine within 182 days
             before Study Day 0

         13. Received investigational TB vaccine, other than BCG

         14. Planned administration/administration of a licensed vaccine in the period starting 28
             days before and ending 28 days after each dose of study vaccine

         15. History or laboratory evidence of any past or present possible immunodeficiency state
             not limited to any lab indication of HIV-1 infection

         16. History of allergic disease likely to be exacerbated by any component of the study
             vaccine

         17. History of alcohol or drug abuse

         18. All female subjects: currently pregnant or lactating/nursing; or positive urine
             pregnancy test during screening

         19. Received a (TST) within 3 months (90 days) prior to Study Day 0.

         20. Any current medical, psychiatric, occupational, substance abuse problems problems that
             in opinion of investigator will make unlikely for the subject to comply with the
             protocol