A Phase III Study of the Safety and Efficacy of Viramidine Versus Ribavirin in Treatment-Naive Patients with Chronic Hepatitis C: ViSER1 Results

被引:38
作者
Benhamou, Yves [1 ]
Afdhal, Nezam H. [2 ]
Nelson, David R. [3 ]
Shiffman, Mitchell L. [4 ]
Halliman, Deanine G. [5 ]
Heise, Jamie [5 ]
Chun, Eric [5 ]
Pockros, Paul J. [6 ]
机构
[1] Hop La Pitie Salpetriere, Serv Hepatogastroenterol, F-75651 Paris, France
[2] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA
[3] Univ Florida, Dept Med Hepatol & Liver Transplantat, Gainesville, FL USA
[4] Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA
[5] Valeant Pharmaceut, Aliso Viejo, CA USA
[6] Scripps Clin, Div Gastroenterol Hepatol, La Jolla, CA 92037 USA
关键词
INTERFERON-ALPHA-2B PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2B; PEGYLATED INTERFERON-ALPHA-2B; VIROLOGICAL RESPONSE; TARIBAVIRIN EXPOSURE; COMBINATION THERAPY; RANDOMIZED-TRIAL; VIRUS-INFECTION; ANEMIA; HCV;
D O I
10.1002/hep.23073
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Pegylated interferon (peg-IFN) and ribavirin (RBV) are effective in eradicating the hepatitis C virus in more than half of patients. However, anemia arising from RBV-induced hemolysis can prompt dose reductions and lower sustained virologic response (SVR) rates. In early clinical trials, Viramidine (VRD, renamed taribavirin), an RBV prodrug, was associated with less anemia and VRD given at 600 mg twice daily (BID) appeared to provide the best safety with comparable efficacy to RBV. The phase III Viramidine's Safety and Efficacy versus Ribavirin 1 (ViSER1) study randomized 972 treatment-naive patients with chronic hepatitis C to fixed-dose VRD (600 mg BID) or weight-based RBV (1000 or 1200 mg/day), each given with peg-IFN alfa-2b at 1.5 mu g/kg/week The primary efficacy endpoint was SVR rate, and the primary safety endpoint was hemoglobin (Hb) event rate (percent of patients with Hb < 10 g/dL or at least a 2.5-g/dL decrease from baseline). SVR rates were 37.7% with VRD (244/647) and 52.3% with RBV (170/325). Thus, the ViSER1 study failed to demonstrate the primary noninferiority efficacy endpoint. Significantly fewer patients had Hb events with VRD (353/647; 54.6%) compared to those with RBV (272/325; 83.7%) (P < 0.001), and significantly fewer developed anemia (Hb < 10 g/dL) with VRD (34/647; 5.3%) compared to those with RBV (76/325; 23.5%) (P < 0.001). Conclusion: Fixed doses of VRD failed to demonstrate noninferiority to RBV in producing SVR rates. The incidence of anemia was approximately four-fold significantly lower with VRD than with RBV. These results suggest fixed-dose VRD given 600 mg BID is insufficient to treat patients with chronic hepatitis Q a weight-based dosing trial of viramidine is currently under way. (HEPATOLOGY 2009;50:717-726.)
引用
收藏
页码:717 / 726
页数:10
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