Safety and Immunogenicity Study of BCG, H4:IC31, and H56:IC31 Revaccination in Healthy Adolescents
Condition: Tuberculosis
MeSH terms: Tuberculosis
Intervention: H4:IC31; H56:IC31; BCG; Control Sodium Chloride 0.9%
Intervention description: H4 contains Mtb antigens Ag85B and TB10.4; H56 contains Mtb antigens ESAT-6, and Rv2660c
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 84.0
Sex: All
Minimum age: 12 Years
Maximum age: 17 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      The aims of the phase 1b trial described here are to facilitate identification of assays and
      immune responses that could then be evaluated as correlates of risk and correlates of
      protection in efficacy studies and ultimately to provide leads for biomarkers of protection
      against tuberculosis. This study will complement one ongoing study (NCT02075203) evaluating
      the prevention of M. Tuberculosis infection using H4:IC31 (also known as AERAS-404).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Age of 12 to ≤ 17 years at enrollment

          2. Minimum weight ≥ 40 kg

          3. Previous BCG vaccination at least 5 years ago documented by scarification or medical
             card

          4. No evidence of active TB disease, as determined by history, physical examination and,
             if deemed appropriate, sputum investigation and / or chest x-ray.

          5. Negative QFT-GIT test at screening, using the manufacturer's recommended threshold of
             0.35 IU/mL

          6. Assessed by the clinic staff as being at low risk for HIV infection

          7. Hemoglobin ≥ 11.7 g/dL for females, ≥ 12.5 g/dL for males

          8. Negative HIV-1 and -2 blood test

          9. Agree to consistently use effective contraception for sexual activity that could lead
             to pregnancy from at least 20 days prior to enrollment through the last required
             protocol clinic visit.

        (additional minor criteria not added due to space constraints)

        Exclusion Criteria:

          1. Blood products received within 120 days before first vaccination

          2. Investigational research agents received within 182 days before first vaccination

          3. Intent to participate in another study of an investigational research agent during the
             planned duration of the HVTN 602 / AERAS A-042 study

          4. Pregnant or breastfeeding

          5. History of alcohol or drug abuse

          6. A significant contact with active TB disease: for example, shared residency with an
             individual receiving anti-TB treatment, or with an individual known to have
             incompletely treated culture or smear positive TB

          7. TB prophylaxis within 90 days prior to enrollment

          8. History of treatment for active TB disease or latent Mtb infection

          9. Positive and indeterminate QFT-GIT result

         10. Received a tuberculin skin test (TST) within 90 days prior to enrollment

         11. Vaccines and other Injections

         12. Immunosuppressive medications received within 168 days before first vaccination.

         13. Serious adverse reactions to vaccines including history of anaphylaxis and related
             symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain.

         14. Immunoglobulin received within 60 days before first vaccination

         15. Autoimmune disease Not excluded: mild, well-controlled psoriasis

         16. Clinically significant medical condition, physical examination findings, clinically
             significant abnormal laboratory results, or past medical history with clinically
             significant implications for current health. Including but not limited to: Diabetes
             mellitus type 1 or type 2, Thyroidectomy, or Thyroid disease, Asthma, Asplenia,
             Bleeding disorders, malignancy, Seizure disorder, and Angioedema

        (additional minor criteria not added due to space constraints)