TY - JOUR
T1 - Efficacy of boceprevir, an NS3 protease inhibitor, in combination with peginterferon alfa-2b and ribavirin in treatment-naive patients with genotype 1 hepatitis C infection (SPRINT-1)
T2 - An open-label, randomised, multicentre phase 2 trial
AU - Kwo, Paul Y.
AU - Lawitz, Eric J.
AU - McCone, Jonathan
AU - Schiff, Eugene R.
AU - Vierling, John M.
AU - Pound, David
AU - Davis, Mitchell N.
AU - Galati, Joseph S.
AU - Gordon, Stuart C.
AU - Ravendhran, Natarajan
AU - Rossaro, Lorenzo
AU - Anderson, Frank H.
AU - Jacobson, Ira M.
AU - Rubin, Raymond
AU - Koury, Kenneth
AU - Pedicone, Lisa D.
AU - Brass, Clifford A.
AU - Chaudhri, Eirum
AU - Albrecht, Janice K.
N1 - Funding Information:
PYK has received research grants, honoraria, consultancy fees, and travel grants from Schering-Plough/Merck; research grants from Vertex, Tibotec, Roche, Abbott, Bristol-Myers Squibb, Gilead, Idenix, Valeant, GlaxoSmithKline, and Human Genome Sciences; served on advisory boards for Vertex, Gilead, Anadys, Abbott, Human Genome Sciences, and Novartis; and is on the speaker's bureau for Schering Plough/Merck, Roche, Gilead, and Bristol-Myers Squibb. JMV has received research grants from Abbott, Conatus, Excalenz, Gilead, GlobeImmune, Hyperion, Idenix-Novartis, Intercept, Merck/Schering-Plough, Novartis, Ocera, Pharmasset, Pfizer, Sundise, Vertex, and ZymoGenetics; and is on the speakers' bureau for Bristol-Myers Squibb, Chronic Liver Disease Foundation, Gilead, Roche, and Merck. EJL has received research grants from Abbott, Anadys, Biolex, Bristol-Myers Squibb, Gilead, GlaxoSmithKline, GlobeImmune, Human Genome Sciences, Idenix, Idera, Intarcia, Medarex, Medtronic, Merck, Novartis, Pharmasset, Roche, Schering-Plough, Tibotec, Valeant, Vertex, ViroChem Pharma, and ZymoGenetics; and honoraria from Merck. ERS has received honoraria (speaking and advisory boards) and research grants from Abbott, Anadys, Bristol-Myers Squibb, Gilead, GlobeImmune, Merck, Medtronics, Roche Diagnostics, Roche Molecular, Salix, Sanofi-Aventis, Schering-Plough, SciClone, and Vertex; and has served on advisory boards for Bristol-Myers Squibb, Gilead, Johnson & Johnson, Merck, Orasure, and Roche Molecular. SCG has received research support and grants from Abbott, Anadys, Biolex, Bristol-Myers Squibb, Exalenz, Gilead, GlaxoSmithKline, GlobeImmune, Human Genome Science, Merck, Roche, Schering-Plough, SciClone, Tibotec, Vertex, ViroChem Pharma, and ZymoGenetics; is on the speakers' bureau for Gilead, Merck, and Roche; and has received consultancy fees from Dynavax, Gilead, and Merck. MND is on the speakers' bureau of Genentech and Merck, a member of the Roche group; and has received research grants from Schering-Plough and Vertex. NR has received research grants from Schering-Plough. FHA has received research grants from Bristol-Myers Squibb, Gilead, Novartis, Roche, Schering-Plough, ZymoGenetics, Debiopharm, and Pharmasset; has served as an advisor for Bristol-Myers Squibb, Gilead, and Schering-Plough; and has received gifts from Merck and Roche (for nursing support). RR has received research support and honoraria from Schering-Plough, Roche, Vertex, Gilead, Conatus, and Bristol-Myers Squibb. IMJ has received research support and grants from Schering-Plough, Valeant, Gilead, Vertex, GlobeImmune, Human Genome Sciences, Novartis, Boehringer Ingelheim, Anadys, Pharmasset, Roche, Merck, Tibotec, and Romark; consultancy fees from Bristol-Myers Squibb, Novartis, Gilead, Schering-Plough, Pfizer, Vertex, GlobeImmune, Human Genome Sciences, Merck, Boehringer Ingelheim, Pharmasset, ZymoGenetics, Tibotec, Abbott, Roche, Anadys, and Progenics; and is on the speakers' bureau for Roche and Schering-Plough, Gilead, Bristol-Myers Squibb, and Novartis. LR has received grants from and has given lectures for Genentec, Merck, Vertex, Novartis, and Three Rivers; has received honoraria from Genentec, Merck, Vertex, and Three Rivers; and is on the speakers' bureau for Genentech, Schering-Plough, and Three Rivers. JMcC is on the speakers' bureau for Roche and Schering-Plough. KK, LDP, EC, JKA, and CAB are employees and stockholders of Merck. DP has received research support and grants from Schering-Plough and was on the speakers' bureau for Schering-Plough. JSG has received research support and grants from Schering-Plough.
PY - 2010/8/28
Y1 - 2010/8/28
N2 - Background Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin. Methods In part 1 of this trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1·5 μg/kg plus ribavirin 800-1400 mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400-1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00423670. Findings Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54, 95 CI 44-64], p=0·013 for PRB28; 58/103 [56, 44-66], p=0·005 for PR4/PRB24; 69/103 [67, 57-76], p<0·0001 for PRB48; and 77/103 [75, 65-83], p<0·0001 for PR4/PRB44; vs 39/104 [38, 28-48] for PR48 control). Low-dose ribavirin was associated with a high rate of viral breakthrough (16/59 [27]), and a rate of relapse (six of 27 [22]) similar to control (12/51 [24]). Boceprevir-based groups had higher rates of anaemia (227/416 [55] vs 35/104 [34]) and dysgeusia (111/416 [27] vs nine of 104 [9]) than did the control group. Interpretaion In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4-week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone. Funding Merck.
AB - Background Peginterferon plus ribavirin achieves sustained virological response (SVR) in fewer than half of patients with genotype 1 chronic hepatitis C virus infection treated for 48 weeks. We tested the efficacy of boceprevir, an NS3 hepatitis C virus oral protease inhibitor, when added to peginterferon alfa-2b and ribavirin. Methods In part 1 of this trial, undertaken in 67 sites in the USA, Canada, and Europe, 520 treatment-naive patients with genotype 1 hepatitis C virus infection were randomly assigned to receive peginterferon alfa-2b 1·5 μg/kg plus ribavirin 800-1400 mg daily for 48 weeks (PR48; n=104); peginterferon alfa-2b and ribavirin daily for 4 weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir 800 mg three times a day for 24 weeks (PR4/PRB24; n=103) or 44 weeks (PR4/PRB44; n=103); or peginterferon alfa-2b, ribavirin, and boceprevir three times a day for 28 weeks (PRB28; n=107) or 48 weeks (PRB48; n=103). In part 2, 75 patients were randomly assigned to receive either PRB48 (n=16) or low-dose ribavirin (400-1000 mg) plus peginterferon alfa-2b and boceprevir three times a day for 48 weeks (low-dose PRB48; n=59). Randomisation was by computer-generated code, and study personnel and patients were not masked to group assignment. The primary endpoint was SVR 24 weeks after treatment. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00423670. Findings Patients in all four boceprevir groups had higher rates of SVR than did the control group (58/107 [54, 95 CI 44-64], p=0·013 for PRB28; 58/103 [56, 44-66], p=0·005 for PR4/PRB24; 69/103 [67, 57-76], p<0·0001 for PRB48; and 77/103 [75, 65-83], p<0·0001 for PR4/PRB44; vs 39/104 [38, 28-48] for PR48 control). Low-dose ribavirin was associated with a high rate of viral breakthrough (16/59 [27]), and a rate of relapse (six of 27 [22]) similar to control (12/51 [24]). Boceprevir-based groups had higher rates of anaemia (227/416 [55] vs 35/104 [34]) and dysgeusia (111/416 [27] vs nine of 104 [9]) than did the control group. Interpretaion In patients with untreated genotype 1 chronic hepatitis C infection, the addition of the direct-acting antiviral agent boceprevir to standard treatment with peginterferon and ribavirin after a 4-week lead-in seems to have the potential to double the sustained response rate compared with that recorded with standard treatment alone. Funding Merck.
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U2 - 10.1016/S0140-6736(10)60934-8
DO - 10.1016/S0140-6736(10)60934-8
M3 - Article
C2 - 20692693
AN - SCOPUS:77956268467
SN - 0140-6736
VL - 376
SP - 705
EP - 716
JO - The Lancet
JF - The Lancet
IS - 9742
ER -