Oral Presentations
Session Title: OPENING AND GENERAL SESSION 1
Presentation Date: Apr 23, 2009
HCV SPRINT-1 FINAL RESULTS : SVR 24 FROM A PHASE 2 STUDY OF BOCEPREVIR PLUS PEGINTRONTM (PEGINTERFERON ALFA-2B)/RIBAVIRIN IN TREATMENT-NAÏVE SUBJECTS WITH GENOTYPE-1 CHRONIC HEPATITIS C
P. Kwo1, E. Lawitz2, J. McCone3, E. Schiff4, J. Vierling5, D. Pound6, M. Davis7, J. Galati8, S. Gordon9, N. Ravendhran10, L. Rossaro11, F. Anderson12, I. Jacobson13, R. Rubin14, K. Koury15, C. Brass15, E. Chaudhri15, J. Albrecht15
1Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, 2Alamo Medical Research, San Antonio, TX, 3Mount Vernon Endoscopy Center, Alexandria, VA, 4Center for Liver Diseases, University of Miami Miller School of Medicine, Miami, FL, 5Professor of Medicine and Surgery, Baylor College of Medicine, Houston, TX, 6Indianapolis Gastroenterology Research Foundation, Indianapolis, IN, 7Digestive Care/South Florida Center of Gastroenterology, Wellington, FL, 8Liver Specialists of Texas, Houston, TX, 9Department of Hepatology, Henry Ford Health Systems, Detroit, MI, 10Digestive Disease Associates, Baltimore, MD, 11Internal Medicine, University of California-Davis Medical Center, Sacramento, CA, USA, 12The Liver & Intestinal Research Center, Vancouver, BC, Canada, 13Weill Cornell Medical College, New York, NY, 14Digestive Healthcare of Georgia, Atlanta, GA, 15Schering-Plough Research Institute, Kenilworth, NJ, USA
Background: HCV SPRINT-1 assessed the safety and efficacy of boceprevir, an oral inhibitor of HCV-NS3 protease, plus PegIntron (P) (1.5 µg/kg/QW) and ribavirin (R) (400-1400 mg/day).
Methods: P/R(800-1400 mg/day) for 48 weeks compared to five boceprevir(800 mg TID) regimens: 4 weeks of P/R lead-in followed by P/R(800-1400 mg/day)/boceprevir for 24 or 44 weeks; P/R(800-1400 mg/day)/boceprevir for 28 or 48 weeks; and P/low-dose R(400-1000 mg/day)/boceprevir for 48 weeks. The primary endpoint was sustained virologic response (SVR) at 24 weeks post-treatment (Roche TaqMan LLD=15 IU/mL).
Results: Of 595 patients treated in US (77%), Canada and Europe, 60% were male, 16% Black, 7% cirrhotic, 56% genotype 1a and 89% had high viral load (>600,000 IU/mL). SVR was significantly increased in the 28 and 48 week boceprevir arms compared to P/R Control. RVR† and EVR†† were highly predictive of SVR with boceprevir combinations. Rash-related AEs were similar for boceprevir regimens and P/R Control.
| Sustained Viriologic Response % (n/N)* | ||||||
| Treatment Arm | All Patients | Patients with RVR† | Patients with EVR†† | Relapse Rate % (n/N) | Discontunuation due to AE % (n/N) | Viral** Breakthrough % (n/N) |
| P/R Control 48 Weeks | 38% (39/104) | 100% (8/8) | 86% (32/37) | 24% (12/50) | 8% (8/104) | 0 |
| P/R/B 28 Weeks | 55%+ (59/107) | 74% (32/43) | 69% (59/85) | 30% (24/81) | 11% (12/107) | 7% (7/107) |
| P/R Lead-In → P/R/B 28 Weeks | 56%++ (58/103) | 82% (54/66) | 68% (58/85) | 24% (18/76) | 15% (15/103) | 4% (4/103) |
| P/R/B 48 Weeks | 67%+++ (69/103) | 84% (32/38) | 84% (68/81) | 7% (5/73) | 19% (20/103) | 12% (12/103) |
| P/R Lead-In → P/R/B 48 Weeks | 75%+++ (77/103) | 94% (62/66) | 91% (77/85) | 3% (2/79) | 9% (9/103) | 5% (5/103) |
| P/R/B 48 Weeks*** | 50% (8/16) | 86% (6/7) | 73% (8/11) | 11% (1/9) | 25% (4/16) | 25% (4/16) |
| P/Low Dose R/B 48 Weeks*** | 36% (21/59) | 75% (12/16) | 60% 21/35 | 23% (6/26) | 12% (7/59) | 27% (16/59) |
†Undetectable HCV-RNA ≤4 weeks boceprevir
††Undetectable HCV-RNA ≤12 weeks boceprevir
*Per protocol, if ≥ 24 week post-treatment not available, 12 week post-treatment assessment utilized
**Persistent ≥ 2 log10 increase from nadir and ≥50,000 IU/mL
***In Part 2, 75 patients randomized 1:4 to full vs low dose ribavirin plus P/B for 48 weeks
+p=0.0082, ++p=0.0048, +++p< 0.0001 adjusted for baseline stratification
Conclusions: Both 28 and 48 week boceprevir regimens significantly increased SVR with very low relapse rates in 48 week regimens. However, low dose ribavirin with PegIntron and boceprevir was associated with increased viral breakthrough, relapse and lower efficacy. In contrast, P/R lead-in prior to boceprevir substantially increased SVR and reduced viral breakthrough.
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