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A Phase 2b Study of Telaprevir with Peginterferon-Alfa-2a and Ribavirin in Hepatitis C Genotype 1 Null and Partial Responders and Relapsers Following a Prior Course of Peginterferon-Alfa-2a/b and Ribavirin Therapy: PROVE3 Interim Results
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Reported by Jules Levin
AASLD Nov 3 2008 San Francisco, CA
J. G. McHutchison; M. L. Shiffman; N. Terrault; M. P. Manns; A. M. Di Bisceglie; I. M. Jacobson; N. H. Afdhal; E. Heathcote; S. Zeuzem; H. W. Reesink; S. George; N. Adda; A. J. Muir
PROVE3 Interim Analysis: AUTHOR SUMMARY and CONCLUSION
In a population of patients who have failed previous Peg-IFN/RBV therapy, response rates 12 weeks after end of treatment were 52% overall in the T12/PR24 arm:
--73% in prior relapsers
--41% in prior non-responders (they did not present data separate for null-responders)
Lower response rates (21%) in T24?p24 (no RBV) arm are consistent with PROVE2
Adverse events reported more frequently in the TVR-treatment arms versus control were GI events, fatigue, headache, anemia and skin events (rash, pruritis)
-- Other AEs were similar in type and frequency to those seen with Peg-IFN/RBV
--Treatment discontinuations at week 36 due to AEs were:
16% in the TVR-based treatment arms
4% in the control arms
Further data are required from this study and subsequent larger confirmatory studies to further define the use of TVR in patients who did not respond to prior Peg-IFN/RBV treatment
--PR48 (control): placebo + peg/IFN/RBV for 24 weeks, peg/IFN + RBV for 24 additional weeks
--T12/P24 TVR + peg/RBV for 12 weeks plus 12 weeks of pegIFN/RBV
--T24/P24 (no RBV) TVR + Peg/IFN for 24 weeks
--T24/PR48 TVR + peg/RBV for 24 weeks, peg/RBV for additional 24 weeks
TREATMENT STOPPING RULES
Discontinue treatment if on two consecutive occasions HCV RNA testing indicates viral breakthrough defined as:
--an increase in HCV RNA of a >/=1log compared with nadir, or
--an HCV RNA level of >100 IU/mL in a patient with undetectable HCV RNA at a prior timepoint
WEEK 4 non-responder
Control arm: < 1 log HCV RNA decrease from baseline to week 4
TVR arm: detectable HCV RNA (>10 iu/ml)
WEEK 12 (EVR) Non-responder
All arms: <2 log reduction from baseline in HCV RNA at week 12
Week 24 non-responder
Control and T24/PR48 arms: detectable HC RNA at week 24
65-70% men
88-90% Caucasians
8-10% black race
age 50-53 yrs
BMI median 27-28
Median HCV RNA 6.7 to 6.8 logs
HCV genotype: 54-62% 1a, 29-37% 1b
Prior response:
-non-responders 56-60%
- relapsers 35-37%
- breakthroughs 3-9%-
Bridging fibrosis 23-29%
Cirrhosis 11-20%
Week 4
T12/PR24 61%
T24/PR48 50%
T24/P24 (no RBV) 47%
PR48 (control)
Week 12
T12/PR24 (n=118) 75%
T24/P24 (no RBV) (n=111) 53%
T24/P48 (n=113) 66%
PR48 (control) (n=114) 8%
Week 24
T12/P24 70%
T24/PR48 56%
T24/P24 (no RBV) 48%
PR48 (control) 33%
52% undetectable T12/PR24
21% T24/P48
T24/PR48 46% at week 36 of treatment
PR48 (control) 30% at week 36 of treatment
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