Rollover : A Study of Telaprevir (TVR) with Peginterferon alfa-2A (P) and Ribavirin (R) in Subjects with Well-documented Prior P/R Null Response, Non-Response or Relapse: Preliminary Results
Background:
VX06-950-107 is an ongoing open-label study of TVR/P/R in genotype 1 HCV subjects who failed to achieve SVR in the control arms of the TVR Phase 2 studies. Study 107 provides a unique opportunity to correlate within individual subjects the anti-viral response to TVR/P/R with that of their original response to P/R. In this preliminary analysis we evaluated the anti-viral response to TVR/P/R at week 4 in non-responders to P/R.
Methods:
Null-responders (NR) (<1 log10 decrease at week 4 or < 2 log10 decrease at week 12),
Non-responders at W24 (HCV RNA detectable) and
Relapsers from the P/R arms of PROVE studies were eligible.
Study dosing consisted of 12 weeks TVR + P/R at standard doses, followed by 12 weeks P/R.
In this study, subjects with HCV RNA >25IU/mL (Taqman™ assay; LOQ 25 IU/mL) at Week 4 met a stopping rule and discontinued.
Results:
To date 54 subjects were enrolled, 52 were dosed and 32 completed Week 4 assessment: 24 male/8 female with median age of 51.5 years, 28 Caucasians, 3 Blacks, 1 Hispanic. Median baseline HCV RNA was 6.9 Log10IU/ml. 1 subject discontinued TVR and R due to fatigue.
Results by prior virologic response to P/R regimen are summarized below:
Conclusions:
With TVR/P/R,
70% (14/20) of null responder subjects and
100% (7/7) of Week 24 detectable and
100% (4/4) relapsers to P/R achieved < 25 IU/mL at week 4.
Only one subject had a virologic breakthrough.
These results are promising, however SVR rates are yet to be determined.
PROVE1: Results From A Phase 2 Study Of Telaprevir With Peninterferon alfa-2a And Ribavirin In Treatment Naive Subjects With Hepatitis C
Background: PROVE1 is a randomized, placebo-controlled Phase 2 study of750 telaprevir (TVR) with Peg-IFN-alfa-2a (P) and ribavirin (R), in naive subjects with genotype 1 hepatitis C.
250 subjects were randomized into 4 groups:
175 subjects received TVR/PR for 12wks followed by
PR for 0 weeks (D:12wk:TVR/PR, n=17)
PR for 12weeks (C:24wk:TVR/PR, n=79) or
PR for 36weeks (B:48wk:TVR/PR, n=79);
the control group (A:48wk:PR, n=75) received 48wks of PR.
Methods:
ITT analysis was performed when all subjects completed treatment and 24-week post-treatment follow-up.
Results:
Week 4 undetectable HCV RNA (LOD 10 IU/mL) in all TVR/PR groups compared to the control group (RVR: 79% vs 11%) and at week 12 (70% vs 39%).
During the first 12wks, 9% of subjects in the TVR/PR groups never reached undetectable HCV RNA levels compared to 57% of subjects in the PR group.
At the EOT, the proportion of subjects with undetectable HCV RNA was substantially higher in the 48wk: TVR/PR group (B) than in the 48wk: PR control group (65% vs 45%)
The SVR rate for subjects in the 24wk: TVR/PR group (C) was substantially higher than in subjects in the 12wk: TVR/PR group (D) (61% vs 35%).
svr rate - 61% in 24 week arm - 35% in 12 week arm
The relapse rate in patients with RVR who completed 12, and 24 weeks of therapy was 3/9 (33%) and 1/42 (2.4%), respectively.
Adverse events (AEs) leading to discontinuations were more frequent in the TVR/PR groups (13% vs. 3%). Rashes, gastrointestinal events and anemia were more common, and rashes more severe in the TVR/PR groups.
Grade 3 AEs were reported in 27.4% of subjects in the TVR/PR groups, and 24% of subjects in the PR control group.
11.4% of the subjects in the TVR/PR groups reported serious AEs compared to 5.3% in the PR control group.
Conclusions:
Compared with current treatment, TVR-based therapy resulted in a high rate of RVR and subsequent on-treatment response rate. These results suggest potential for higher SVR rates with shorter duration of therapy in subjects with genotype 1The final analysis will be executed when all subjects have completed 24-week post-treatment follow-up.
PROVE 2: Treatment of Chronic Hepatitis C with Telaprevir (TVR) in Combination with Peginterferon-alfa-2a with or without Ribavirin: Further Interim Analysis Results of the PROVE2 Study
Methods: 323 patients randomized.
*Control arm: Peg180 mcg/weekly, ribavirin 1000-1200 mg, TVR-placebo 48 weeks.
*24-week arm: TVR 750 with P/R for 12-weeks, P/R a further 12 weeks.
*12-week arm: TVR 750 with P/R for12 weeks.
*No Riba arm: TVR/P 12 weeks.
Plasma HCVRNA was quantified by the Roche Taqman™ assay (LOD 10 IU/mL).
Results:
*10% of patients in the TVR/P/R arms discontinued due to AEs in the first 12-weeks.
*Pruritus, nausea, rash, anemia were 10% more frequent in TVR arms versus controls, rash was grade-III in 6%, other AEs ? 2%.
* In patients experiencing rash, 7% discontinued in the 12/24-week arms, 3% in the no R arm, none in controls.
Table summarizes ITT viral outcomes at week 4 and 12 with 12-week follow up for the 24-week arm, 24-week follow up results for 12-week and no R arms.
Total relapse rates, in patients completing 12 and 24-weeks, were 28% and 14%, respectively, but 22% and 11% in those with RVR.
Undetectable HCV RNA at:
Arms .......week4 ......week12...... 12* or 24** weeks follow up
Control....... 13% ........42% ............ongoing
24-Week ....69% ........73%............ 65%*
12-Week ....80%.........79% ............59%**
No Riba....... 51% ........62%............ 29%**
SVR rates for patients in the 24-week, 12-week and no Ribavirin arms, and, 12-week follow up data for patients in the control arm will complete outcome assessments in the April 2008 time-point
