Update on the TESEC trials Development of a novel Mtb skin test

Transcription

1 ESM Brasov 2012 TALLER UITB-2013 Update on the TESEC trials Development of a novel Mtb skin test Søren Tetens Hoff MD, PhD. Research Scientist Human Immunology Department of Infectious Disease Immunology Statens Serum Institut (SSI) Copenhagen, Denmark 1

2 WHAT ARE THE TESEC TRIALS? Series of clinical trials sponsored by Statens Serum Institut EMA approval of C-Tb a novel skin test for Mtb infection T-spot.TB QuantiFERON TB Gold in tube Non-tuberculous Mycobacteria 2

3 THE C-TB BASIC IDEA OF C-TB PPD Tuberculin Skin Test Well known technology Easy to use (no lab) No blood draw Low cost per test IGRA High specificity C-Tb Well known technology Easy to use No blood draw Low cost per test High specificity 3

4 CLINICAL DEVELOPMENT OF C-Tb PHASE I & II Phase I Completed TESEC healthy adults Safety No sensitization Denmark TESEC adult TB patients Safety Dose finding (0.01 and 0.1 ug) No Influence of 0.5% phenol as preservative UK Phase II Completed TESEC-03 Specificity 147 BCG vaccinated adults UK TESEC-04 Sensitivity 241 adult TB patients HIV-and HIV+ South Africa Cut-off for phase III 4

5 TESEC-03 AND -04 TESEC-03 Specificity 147 BCG vaccinated adults UK C-Tb in one arm PPD in the other Quantiferon C-Tb PPD

6 TESEC-03 AND -04 TESEC-03 Specificity 147 BCG vaccinated adults UK TESEC-04 Sensitivity 241 adult TB patients HIV-and HIV+ South Africa C-Tb in one arm PPD in the other 5 mm Quantiferon BCG TB

7 CLINICAL DEVELOPMENT OF C-Tb PHASE III Phase III FPFV Q TESEC-06 Confirmatory study of diagnostic performance of C-Tb compared to QFT and PPD Safety Exposure gradient design: TB patients, Close Contacts Occasional Contacts Un-exposed Controls 950 Adults and children at all age groups Spain 26 randomized 678 randomized TESEC-05 Diagnostic performance of C-Tb in Children and HIV infected Safety TB suspects/contacts and nonexposed 1175 at all age groups (including 600 children and min. 300 HIV infected) South Africa TESEC-07 Diagnostic performance of C-Tb injected alone or concomittant with PPD Safety 450 Adult Confirmed TB patients HIV neg and HIV pos South Africa 7

8 How to design a Phase III efficacy study? C-Tb is a drug we need to follow EMA guidelines and obtain EMA approval Need to show diagnostic performance Simply use TB patients and assumed un-exposed controls Trial population should be representative of the intended target population No gold standard!

9 TESEC-06 DESIGN % C-Tb positive Trend over the groups Superior Specificity to PPD Comparable to QFT Latent Class statistics TB Close Occasional Neg. Controls Exposure gradient C-Tb in one arm PPD in the other Quantiferon

10 TESEC-06 TRIAL

11 TESEC-06 TRIAL

12 TESEC-06: STATUS

13 VISIT 1: SCREENING VISIT Hospital Vall d Hebron CAP Drassanes, Unitat de Prevencio I Control de Tuberculosi Informed consent Medical history BCG, HIV status etc.

14 VISIT 1: SCREENING VISIT General medical examination CAP Drassanes, Unitat de Prevencio I Control de Tuberculosi Hospital del Mar

15 VISIT 2: INCLUSION AND INJECTION Hospital Universitario Lucus Augusti Randomization

16 VISIT 2: INCLUSION AND INJECTION Injections Marking of injection site etc Agencia de Salut Publica de Barcelona

17 VISIT 2: INCLUSION AND INJECTION Quantiferon testing Agencia de Salut Publica de Barcelona

18 VISIT 3: FOLLOW UP Double reading of injection sites Digital images Recording of AEs Hospital del Mar

19 VISIT 3: FOLLOW UP Hospital Universitario Lucus Augusti Hospital Vall d Hebron

20 VISIT 4: FOLLOW UP Double reading of injection sites Digital images Recording of AEs Safety blood tests Hospital Universitario de Cruces

21 A LOT OF WORK FOR MANY DEDICATED PEOPLE!

22 WHY DIAGNOSE LATENT TB AT ALL? Immune recognition of MTB Latent TB In-vivoskintest is more than IFNg X Prognostic value is not tested in the TESEC trials X TB disease Stefan H.E. Kaufmann Review Immunity

23 SUMMARY C-Tb is a novel skin test for Mtb infection Phase II results show Superior specificity to PPD Similar performance as QFT Currently in phase III in Spain and South Africa TESEC-06: Large multi-center study ongoing in Spain Aim to Submit to EMA in January 2016

24 THANKS Dr. Joan A. Cayla, National Coordinator Send me an STATENS SERUM INSTITUT Vaccine development, VUA Erik Carp Bettine Borregaard Dept. Infectious Disease Imm. Regulatory Affairs Quality Control Quality Assurance Fill and Finish Business Development PI s and Investigators at the trial sites -and a special thanks to the staff end especially the Nurses at all the trial sites DSMB Sergio Sevilla Gustau Morera Catherine Lund, Hesri van staden and others from OnQ Dr. Keertan Dheda Prof. Diacon Prof. Åse Bengaard Andersen and others Prof. David Lewis and others -and others