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TMC114-C213 study
Week 24 primary analysis
Highly Treatment Experienced Patients
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C Katlama, MTM Carvalho, D Cooper, K De Backer,
E Lefebvre, R Pedro, K Rombouts, A Stoehr,
T Vangeneugden, A Woehrmann
"POWER: Performance Of TMC114/r When evaluated in 3-class-Experienced patients with PI Resistance"
SUMMARY:
--Patients (n = 318) had received a mean of four prior PIs.
--Baseline values were comparable across all groups: mean VL was 4.48 log10 copies/mL and CD4 was 179 cells/mm3;
--13%, 31% and 56%, respectively had 1, 2 or >3 primary PI mutations.
--OBR contained >1 active NRTI(s) in 79% of all patients.
--During the study, 10% of TMC114/r patients discontinued vs 62% of controls (control discontinuations mainly occurred for virologic failure).
Efficacy data are presented for the TMC114/r dose selected for treatment-experienced patients (600/100 mg bid vs control):
--At Week 24, the mean CD4 increase from baseline was 124 cells/mm3 for TMC114/r vs 20 cells/mm3 for control (p < 0.001).
--The primary endpoint of >1 log10 VL reduction from baseline was achieved in 77% of TMC114/r patients vs 25% for control (p < 0.001).
--Mean VL decrease for TMC114/r was 2.03 vs 0.63 log10 copies/mL for control (p < 0.001).
--VL < 50 copies/mL occurred in 53% of TMC114/r patients vs 18% of controls (p < 0.001).
--VL < 50 copies/mL was achieved in 63% of the 19 TMC114/r patients who
received ENF in their OBR (previously ENF-naïve), vs 56% of the 34 TMC114/r patients who did not receive ENF.
--the antiviral response appeared preserved in patients with 3 or more primary PI mutations:
1 primary PI mutation: -2.70 log for TMC114/r 600/100 bid (n=5) vs -1.02 log for control group (n=9).
2 primary PI mutations: -1.96 log for TMC114/r bid (n=26), vs -0.92 for control group (n=16); 3 primary PI mutations: -1.97 log for TMC114/r 600/100 bid (n=29), vs -0.41 for control group (n=35).
The study authors concluded: The magnitude of viral suppression achieved with TMC114/r in 3-class-experienced patients was significantly greater than
control PI(s) and similar to that seen in less treatment-experienced patients. An exceptional CD4 response was observed.
Dose selected for treatment-experienced patients: TMC114/r 600/100 mg bid
BACKGROUND
Phase IIB studies include TMC114-C213 (POWER 1) (non-US*) and TMC114-C202 (POWER 2) (United States). These studies are randomized controlled evaluation of 4 doses of TMC114/r in 3-class-experienced patients with evidence of PI resistance. The target enrollment is 300 patients/study (60 patients/arm)
At CROI 2005 results from half the study population from each of Power 1 & 2 were pooled for the presentation. This study data from IAS is the full 24-week results for POWER 1.
STUDY DESIGN
Patients were 3-class experienced with at last 1 PI mutation, viral load >1000 copies/ml. Patients were randomized to one of 4 arms containing TMC114/r or to a control arm in which patients received investigator selected PIs plus OBR-optimized background regimen. Upon protocol defined viral failure, patients in the control arm were allowed into a separate rollover arm.
4 TMC114/r Regimens
TMC114/r 400/100 once daily +OBR
TMC114/r 800/100 once daily +OBR
TMC114/r 400/100 twice daily +OBR
TMC114/r 600/100 mg twice daily (THIS IS THE REGIMEN SELECTED FOR FURTHER DEVELOPMENT.
DISCONTINUATIONS
In the TMC114/r patient groups 10% of 255 study participants discontinued: 5% for adverse events, 4% for viral failure, 1% withdrew/other. In the Control patient group 62% of 63 patients discontinued: 6% for AE, 54% for viral failure, 2% withdrew/other.
PROPORTION OF PATIENTS WITH 1 LOG REDUCTION IN VIRAL LOAD
TMC114/r 600/100 bid: 77%*
TMC114/r 800/100 qd: 72%*
TMC114/4 400/100 qd: 70%*
TMV114/r 600/100 bid: 69%*
*p<0.001 vs control.
CHANGE FROM BASELINE IN HIV RNA
The TMC114/r dose achieved the greatest decline in viral loa, -2.03 log.
The 800 qd dose: -1.83 log
400 qd: -1.78
400 bid: -1.69
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