The novel C-Tb skin test for LTBI · • 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

The novel C-Tb skin test for LTBI

Peter Andersen

VP vaccine R/D

Statens Serum Institut

Copenhagen, Denmark

1

C-TBTHE C-Tb SKINTEST

2

C-Tb combines the simplicity and low cost of the skin test with the

diagnostic accuracy of the IGRA tests

ESAT-6

CFP-10

ESAT-6

CFP-10

PPD

BCG & non-tuberculous mycobacteria

C-TBC-Tb IS Mtb-SPECIFIC

3

C-Tb

C-Tb & IGRAs are both based on purified ESAT-6 and CFP-10

PPD

ESAT-6

CFP-10

Mtb

C-Tb IN CLINICAL DEVELOPMENT

4

ReportingTESAT trials(rdESAT-6)

TESEC-01

TESEC-07

TESEC-05

TESEC-02 TESEC-03

TESEC-04

TESEC-06

SEVEN CLINICAL TRIALS

3,109 participants

723 children

867 HIV-infected

ID of commercial

partner

Phase II Phase IIIPhase I Phase I

Partnership

Phase III results

Toxicology incl. embryo-fetal toxicity

2007 20172008 2009 2010 2011 2012 2013 2014 2015 2016

Lillebaek et al, Tuberculosis 2009; Arend et al, Tuberculosis 2008; Aggerbeck et al, PlosOne 2013; Hoff et al, ERJ 2016

5

C-TB CUT-OFF

Optimal cut-off: ≥ 5mm

ROC curve analysis

BC

G c

on

tro

ls

TB

pat i

en

ts

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0

9 0

1 0 0

P P D

Ind

ura

tio

n

(mm

)

5

BC

G c

on

tro

ls

TB

pat i

en

ts

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0

9 0

1 0 0

C -T b

Ind

ura

tio

n

(mm

)

5

Aggerbeck et al, PlosOne 2013; Hoff et al, ERJ 2016

BCG controls N=153 (all HIV-)

TB patients N=241 (146 HIV- and 95 HIV+)

UNIVERSAL CUT-OFF OBVIATE CONFLICTING TST GUIDELINES

Cut-off for PPD-TST depends on:

Local guidelines

BCG* vaccination status

Clinical context incl. HIV infection and age

6

5 10 15 mm0

*Bacillus Calmette-Guérin, tuberculosis vaccine

Introduces risk of bias and

uncertainty of infection status

CONCLUSIONS & RESULTS FROM PHASE 3

7

• 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