Interim analysis of a doubleblind, placebocontrolled study with TMC207 in patients with MultiDrug Re

1
Interim analysis of a double-blind,
placebo-controlled study with TMC207 in patients
with Multi-Drug Resistant (MDR) Tuberculosis

• Karel de Beule, CDTL TMC 207

2
TMC207-C208 Trial Design

• Phase II, placebo-controlled, double-blind
• Patients with newly diagnosed smear positive
  MDR-TB
• Stratified by trial site and degree of lung
  cavitation
• 2 stage trial design
• Stage 1 - Safety and dose determination
• 8 weeks dosage TMC207/placebo and BR, then BR and
  24 months follow-up
• Dose regimen 400 mg qd for 2 weeks followed by
  200 mg three times weekly for 6 weeks
• Stage 2 - Recruiting - full 6 month dosage
• This presentation is a pre-planned analysis of
  the stage 1 results after 8 weeks of treatment

3
Stage 1 Objectives

• Primary
• Evaluate PK (adequacy of the model predicted
  exposure)
• Evaluate safety and tolerability of TMC207
  compared to placebo
• Secondary
• Evaluate anti-bacterial activity of TMC207 at 8
  wks vs placebo

4
Inclusion/Exclusion Criteria

• Male and female 18-65 years
• Positive sputum smear gt 1
• Confirmed resistance to H and R
• HIV negative or HIV with CD4 gt 300 and no ART
• No previous 2nd line anti-tuberculosis agents
• No significant extrapulmonary TB or concomitant
  illness

5
Demographics
6
Background Regimen
7
PK of TMC207 vs model predictions
CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING
8
Most frequent Adverse Events
CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING
9
Safety
CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING
10
Microbiology parameters

• Weekly sputum collection - culture conversion in
  liquid media
• Defined as 2 consecutive negative cultures at
  least 1 week apart
• Drug carry-over effects were prevented
• Analysis set 44 patients (3 withdrawals)
• Serial sputum colony counting (SSCC) performed
  in 22 patients in overnight sputum collections

11
Culture conversion in liquid media
CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING
12
Mean log10 CFU count over time
CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING
13
Conclusions
CONFIDENTIAL RESULTS ONLY FOR UK-CAB MEETING
14
Acknowledgements

• - The patients who participated in our study
• - Dr. Andreas Diacon and team, Stellenbosch
  University, Cape Town
• - Dr. Alexander Pym and team Medical Research
  Council, Durban
• - Dr. Martin Grobusch and team, University of the
  Witwatersrand
• - Dr. Martin Bogoshi and team, Aurum Health,
  South Africa
• - Dr. Renée Krause, C. Pistorius and team,
  QdotPharma, South Africa
• -Members of the TMC207 compound development and
  clinical teams, Tibotec, Yardley, PA (USA) and
  Mechelen, Belgium.