EMaBS TB Vaccine Study
Condition: Safety; Immunogenicity
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      The study will commence with a dose-escalation and age de-escalation study in healthy adults
      and adolescents from the previous Entebbe Mother and Baby Study (EMaBS) in Entebbe, Uganda,
      focusing on ChAdOx1 85A, to provide safety data for ChAdOx1 85A in this population. These
      measures are not required for MVA85A since this vaccine has been more widely used, including
      among adolescents in Uganda, and the dose has been standardised. ChAdOx1 85A dose escalation
      and age de-escalation will be followed by a Phase IIa randomised trial comparing the
      immunogenicity of ChAdOx1 85A and MVA85A with the immunogenicity of BCG revaccination.
      ChAdOx1 85A and MVA85A will be administered via the intramuscular route. The target dose for
      the Phase IIa trial is 2.5x10^10 viral particles (vp) because the lower dose is expected to
      have lower immunogenicity, based on the Oxford study, TB034. Data from the Oxford study
      suggest that this dose will be well tolerated. However, if this dose is not tolerated then
      the lower dose will be used. The dose of MVA85A will be 1 x 10^8 plaque-forming units (pfu)
      in the groups in which it is given. There will be 6 study groups with 3 to 30 volunteers in
      each group.

      Dose escalation for ChAdOx1 85A in adults Group 1:

      The first three adults will receive ChAdOx1 85A at 5 x10^9 vp.

      Group 2:

      The next three adults will be enrolled after safety data has been reviewed by the trial
      management team to one week after ChAdOx1 85A vaccination in group 1. These adults will
      receive ChAdOx1 85A at 2.5 x10^10 vp.

      Age de-escalation and dose escalation for ChAdOx1 85A in adolescents Group 3:

      The first three adolescents will be enrolled after safety data has been reviewed to one week
      after ChAdOx1 85A vaccination in group 2. These three adolescents will receive ChAdOx1 85A at
      5 x10^9 vp Group 4. The next three adolescents will be enrolled after safety data has been
      reviewed to one week after ChAdOx1 85A vaccination in group 2. These three adolescents will
      receive ChAdOx1 85A at 2.5 x10^10 vp.

      Randomised comparison of ChAdOx1 85A-MVA85A versus BCG revaccination:

      Once safety data has been reviewed for groups 1 to 4 to one week post ChAdOx1 85A
      vaccination, recruitment to the randomised trial will commence. Sixty adolescents will be
      randomised, 30 (group 5) to receive ChAdOx1 85A at 2.5 x10^10 vp followed by MVA85A boost and
      30 (group 6) to receive BCG revaccination.

      BCG will be obtained from the Serum Institute of India, an approved provider for Uganda, and
      used at the standard dose of 0.1mL. BCG will be given intradermally.
    

Detailed description: 
      This trial will be financed by a research grant from Medical Research Council. The reference
      number of the grant held by MRC-UKRI is MC_UU_00027/5.
    

Intervention name(s): ChAdOx185A; MVA85A; BCG
Intervention type(s): Biological; Biological; Biological
Intervention description(s): ChAdOx1 85A is an adenoviral vaccine based on a vector that is a chimpanzee adenovirus isolate Y25 expressing the M.tb antigen 85A. Adenoviruses are attractive candidates for use as viral vectors and have been used as vaccine vectors for a number of conditions; however, the use has been limited by the high level of anti-vector immunity present in humans in whom adenovirus is a ubiquitous infection. This has led to the consideration of simian adenoviruses, which are not known to cause pathology or illness in humans and to which the prevalence of anti-vector antibodies is low. The ChAdOx1 vector has been developed by the University of Oxford and been used with different inserts for vaccination, for example the vaccine ChAdOx1 NP+M1 has demonstrated an excellent safety profile in the Influenza trial FLU004. A BCG - ChAdOx1 85A - MVA85A prime boost regime is more protective than BCG alone in mice.; Modified vaccinia virus Ankara (MVA) is a highly-attenuated strain of vaccinia virus which cannot replicate in human cells. It is known to be highly immunogenic in UK adults but has been less immunogenic in African children and infants. It is suitable for use as a viral vector in a prime-boost regime in new vaccine development. It has an excellent safety record as it was administered intradermally to approximately 120,000 people during the smallpox eradication campaign, and has since been used in numerous clinical trials of candidate vaccines against viral, mycobacterial and protozoal infections.; BCG is the only vaccine currently approved for use against Tuberculosis.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: BCG; Tuberculosis; Vaccination