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Interim analysis of a doubleblind, placebo-controlled
study with TMC207 in patients
with Multi-Drug Resistant
(MDR) Tuberculosis
Karel de Beule, CDTL TMC 207
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
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
Inclusion/Exclusion Criteria
•
•
•
•
•
•
Male and female 18-65 years
Positive sputum smear > 1+
Confirmed resistance to H and R
HIV negative or HIV+ with CD4+ > 300 and no ART
No previous 2nd line anti-tuberculosis agents
No significant extrapulmonary TB or concomitant illness
Demographics
Gender - male (%)
Placebo
N=24
71
TMC207
N=23
78
Age - median (yrs)
33
33
HIV negative (%)
88
87
51.4
50.0
Body weight - median (kg)
Background Regimen
Ethionamide
Kanamycin/amikacin
Pyrazinamide
Ofloxacin
Ethambutol
Terizidone/cycloserine
Para-aminosalicylic acid
Placebo
% (N=24)
100
100
100
95.8
62.5
66.7
4.2
TMC207
% (N=23)
100
100
100
100
60.9
52.2
0
PK of TMC207 vs model predictions
CONFIDENTIAL RESULTS ONLY FOR
UK-CAB MEETING
Most frequent Adverse Events
CONFIDENTIAL RESULTS ONLY FOR
UK-CAB MEETING
Safety
CONFIDENTIAL RESULTS ONLY FOR
UK-CAB MEETING
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
Culture conversion in liquid media
CONFIDENTIAL RESULTS ONLY FOR
UK-CAB MEETING
Mean log10 CFU count over time
CONFIDENTIAL RESULTS ONLY FOR
UK-CAB MEETING
Conclusions
CONFIDENTIAL RESULTS ONLY FOR
UK-CAB MEETING
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.