The novel C-Tb skin test for LTBI Peter Andersen VP vaccine R/D Statens Serum Institut Copenhagen, Denmark 1 CTHE-TB C-Tb SKINTEST C-Tb combines the simplicity and low cost of the skin test with the diagnostic accuracy of the IGRA tests PPD ESAT-6 CFP-10 ESAT-6 CFP-10 2 C-TBTb IS Mtb-SPECIFIC C-Tb & IGRAs are both based on purified ESAT-6 and CFP-10 PPD C-Tb ESAT-6 CFP-10 Mtb BCG & non-tuberculous mycobacteria 3 C-Tb IN CLINICAL DEVELOPMENT Phase I Phase I Phase II Phase III 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 Phase III results TESAT trials TESEC-01 TESEC-02 TESEC-03 TESEC-06 Reporting (rdESAT-6) ID of TESEC-04 TESEC-05 commercial Toxicology partner incl. embryo- fetal toxicity TESEC-07 Partnership SEVEN CLINICAL TRIALS 3,109 participants 723 children 867 HIV-infected Lillebaek et al, Tuberculosis 2009; Arend et al, Tuberculosis 2008; Aggerbeck et al, PlosOne 2013; Hoff et al, ERJ 2016 4 C-TB CUT-OFF P P D C -T b 1 0 0 1 0 0 9 0 9 0 8 0 8 0 7 0 7 0 ROC curve analysis n 6 0 n 6 0 o o i ) i ) t t a m a m r 5 0 r 5 0 m u m u ( ( d d n n I 4 0 I 4 0 3 0 3 0 Optimal cut-off: ≥ 5mm 2 0 2 0 1 0 1 0 5 5 0 0 s s s l t l ts o n o n tr e r i t ie n t n t o a a c p o c p G B B T G C C T B B BCG controls N=153 (all HIV-) TB patients N=241 (146 HIV- and 95 HIV+) Aggerbeck et al, PlosOne 2013; Hoff et al, ERJ 2016 5 UNIVERSAL CUT-OFF OBVIATE CONFLICTING TST GUIDELINES Cut-off for PPD-TST depends on: Local guidelines Introduces risk of bias and BCG* vaccination status uncertainty of infection status Clinical context incl. HIV infection and age 0 5 10 15 mm *Bacillus Calmette-Guérin, tuberculosis vaccine 6 CONCLUSIONS & RESULTS FROM PHASE 3 • C-Tb test results correlate with exposure to M. tuberculosis • C-Tb and QFT have similar positivity rates • C-Tb is only impacted by HIV-infection with low CD4 counts (<100 cells/uL) • C-Tb induration size is impacted by young age on a level with PPD • C-Tb deliver IGRA like performance in the field friendly skin test format using a universal 5mm cut off 7.