Abstract | | | | | | | TELAPREVIR IN HEPATITIS C GENOTYPE-1-INFECTED PATIENTS WITH PRIOR NON-RESPONSE, VIRAL BREAKTHROUGH OR RELAPSE TO PEGINTERFERON-ALFA-2A/B AND RIBAVIRIN THERAPY: SVR RESULTS OF THE PROVE3 STUDY | | | | M. Manns1, A. Muir2, N. Adda3, I. Jacobson4, N. Afdhal5, J. Heathcote6, S. Zeuzem7, H. Reesink8, N. Terrault9, M. Bsharat3, S. George3, J. McHutchison2, A. Di Bisceglie10 | | 1Medical School Hannover, Hannover, Germany, 2Duke University Medical Center, Durham, 3Vertex Pharmaceuticals, Cambridge, 4Weill Cornell Medical College, New York, 5Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, USA, 6University of Toronto, Toronto, Canada, 7Johann Wolfgang Goethe University Hospital, Frankfurt/Main, Germany, 8Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, 9University of California San Francisco, San Francisco, 10Saint Louis University School of Medicine, Saint Louis, USA | | | Background: PROVE3 is a randomized, placebo-controlled Phase 2 study assessing safety and efficacy of telaprevir (T) plus Peginterferon-alfa-2a (P) ± Ribavirin (R) in HCV genotype 1 patients who previously failed PR treatment.
Methods: Randomization was 1:1:1:1 to: T/PR for 12-wks, then PR for 12-wks (T12/PR24); T/PR for 24-wks, then PR for 24-wks (T24/PR48); T/P for 24-wks (T24/P24); or placebo/PR (P 180µg/wk, R 1000-1200mg/day) for 24-wks, then PR for 24-wks (PR48).
Results: Of 453 patients included in ITT analysis, 418 (92%) had baseline HCV RNA ≥800,000 IU/mL, 196 (43%) had cirrhosis or bridging fibrosis and 40 (9%) were black; 235 (52%) patients completed assigned treatment.
| Patients achieving SVR (undetectable HCV RNA 24-wks after treatment) | T12/PR24
n/N (%) | T24/PR48
n/N (%) | T24/P24
n/N (%) | PR48
n/N (%) | All Patients
(*statistical comparison to PR48) | 59/115 (51)
(p<0.001*) | 59/113 (52)
(p<0.001*) | 26/111 (23)
(p=0.035*) | 16/114 (14) | | Prior Non-responders (never undetectable) | 26/66 (39) | 24/64 (38) | 6/62 (10) | 6/68 (9) | | Prior Relapsers | 29/42 (69) | 31/41 (76) | 16/38 (42) | 8/41 (20) | | Prior Breakthroughs | 4/7 (57) | 4/8 (50) | 4/11 (36) | 2/5 (40) |
[Patients achieving SVR] | Reasons for treatment failure in this study include | T12/PR24
n/N (%) | T24/PR48
n/N (%) | T24/P24
n/N (%) | PR48
n/N (%) | Protocol-defined stopping rules
- Viral breakthrough | 17/115 (15)
12/115 (10) | 26/113 (23)
8/113 (7) | 41/111 (37)
13/111 (12) | 67/114 (59)
1/114 (1) | | Relapse (in treatment completers) | 22/80 (28) | 2/53 (4) | 28/53 (53) | 17/33 (52) |
[Reasons for treatment failure] The most frequent adverse events that occurred with a greater incidence in T12/PR24 or T24/PR48 than PR48 were fatigue, nausea, headache, rash, pruritus, diarrhea, anemia, insomnia, pyrexia, alopecia, and chills. Grade 3 rash was observed in 7 (6%), 5 (4%), 6 (5%) and 1 (1%) patients in T12/PR24, T24/PR48, T24/P24, and PR48, respectively. Grade 3 anemia was observed in 0 (0%), 7 (6%), 1 (1%) and 1 (1%) patients in T12/PR24, T24/PR48, T24/P24 and PR48, respectively. Eleven (10%), 29 (25%), 10 (9%), and 5 (4%) patients discontinued due to AEs in T12/PR24, T24/PR48, T24/P24, and PR48, respectively. Conclusions: SVR rates in all treatment groups receiving T/PR regimens were significantly higher than with PR48. The general safety profile of T12/PR24 was similar to that observed in treatment-naïve patients. The higher relapse rate in T12/PR24 compared with T24/PR48 may warrant a total of 48-wks of PR in treatment-experienced patients. A Phase 3 study evaluating two T12/PR48 regimens is underway. | | |
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