Grazoprevir plus peginterferon and ribavirin in treatment-naive patients with hepatitis C virus genotype 1 infection: a randomized trial

被引：11

作者：

Lagging, M. ^{[1
]}

Brown, A. ^{[2
]}

Mantry, P. S. ^{[3
]}

Ramji, A. ^{[4
]}

Weilert, F. ^{[5
]}

Vierling, J. M. ^{[6
]}

Howe, A. ^{[7
]}

Gendrano, I. N., III ^{[7
]}

Hwang, P. ^{[7
]}

Zhang, B. ^{[7
]}

Wahl, J. ^{[7
]}

Robertson, M. ^{[7
]}

Mobashery, N. ^{[7
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, SE-41346 Gothenburg, Sweden

[2] Imperial Coll Healthcare NHS Trust, St Marys Hosp, London, England

[3] Methodist Dallas Med Ctr, Liver Inst, Dallas, TX USA

[4] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada

[5] Waikato Dist Hlth Board, Hamilton, New Zealand

[6] Baylor Coll Med, Houston, TX 77030 USA

[7] Merck & Co Inc, Kenilworth, NJ USA

来源：

JOURNAL OF VIRAL HEPATITIS | 2016年 / 23卷 / 02期

关键词：

adverse event; clinical trial; direct-acting antiviral drugs; resistance; sustained virologic response; COMBINATION THERAPY; SOFOSBUVIR; BOCEPREVIR; LEDIPASVIR; MK-5172;

D O I：

10.1111/jvh.12464

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Grazoprevir (MK-5172, Merck & Co., Inc.) is a selective inhibitor of the hepatitis C virus (HCV) NS3/4a protease. The aim of this study was to evaluate the safety and efficacy of grazoprevir at doses of 25-100mg/day in combination with peginterferon and ribavirin (PEG-IFN/RBV). In this randomized, dose-ranging, multicentre trial, treatment-naive adults with chronic HCV genotype 1 infection received once-daily grazoprevir 25mg, 50mg or 100mg plus PEG-IFN/RBV for 12weeks. Patients with quantifiable HCV RNA (25IU/mL) at week 4 received an additional 12weeks of PEG-IFN/RBV. The primary endpoint was sustained virologic response (HCV RNA <25IU/mL 12weeks after completing therapy [SVR12]). Eighty-seven patients were randomly assigned and received 1 dose of therapy. Median time to undetectable HCV RNA was 16days in the 100-mg arm and 22days in the 25- and 50-mg arms. All patients except one had HCV RNA undetectable or unquantifiable at week 4 and received 12weeks of therapy. SVR12 was achieved by 13 of 24 (54.2%), 21 of 25 (84.0%) and 23 of 26 (88.5%) patients in the 25-, 50- and 100-mg arms, respectively (per-protocol analysis). Three patients discontinued as a result of nonserious adverse events (AEs) and three patients experienced serious AEs. Transaminase elevations occurred in two patients (one each in the 25- and 100-mg arms). Conclusion: These data support further study of the grazoprevir 100-mg dose. Phase 3 studies of grazoprevir 100mg in combination with elbasvir are currently ongoing (NCT01710501; protocol P038).

引用

页码：80 / 88

页数：9

共 14 条

[1] Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection [J].

Afdhal, Nezam ;

Zeuzem, Stefan ;

Kwo, Paul ;

Chojkier, Mario ;

Gitlin, Norman ;

Puoti, Massimo ;

Romero-Gomez, Manuel ;

Zarski, Jean-Pierre ;

Agarwal, Kosh ;

Buggisch, Peter ;

Foster, Graham R. ;

Braeu, Norbert ;

Buti, Maria ;

Jacobson, Ira M. ;

Subramanian, G. Mani ;

Ding, Xiao ;

Mo, Hongmei ;

Yang, Jenny C. ;

Pang, Phillip S. ;

Symonds, William T. ;

McHutchison, John G. ;

Muir, Andrew J. ;

Mangia, Alessandra ;

Marcellin, Patrick .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (20) :1889-1898

[2] Ledipasvir and Sofosbuvir for Previously Treated HCV Genotype 1 Infection [J].

Afdhal, Nezam ;

Reddy, K. Rajender ;

Nelson, David R. ;

Lawitz, Eric ;

Gordon, Stuart C. ;

Schiff, Eugene ;

Nahass, Ronald ;

Ghalib, Reem ;

Gitlin, Norman ;

Herring, Robert ;

Lalezari, Jacob ;

Younes, Ziad H. ;

Pockros, Paul J. ;

Di Bisceglie, Adrian M. ;

Arora, Sanjeev ;

Subramanian, G. Mani ;

Zhu, Yanni ;

Dvory-Sobol, Hadas ;

Yang, Jenny C. ;

Pang, Phillip S. ;

Symonds, William T. ;

McHutchison, John G. ;

Muir, Andrew J. ;

Sulkowski, Mark ;

Kwo, Paul .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (16) :1483-1493

[3]

[Anonymous], REC TEST MAN TREAT H

[4] Boceprevir for Previously Treated Chronic HCV Genotype 1 Infection [J].

Bacon, Bruce R. ;

Gordon, Stuart C. ;

Lawitz, Eric ;

Marcellin, Patrick ;

Vierling, John M. ;

Zeuzem, Stefan ;

Poordad, Fred ;

Goodman, Zachary D. ;

Sings, Heather L. ;

Poordad, Fred ;

Goodman, Zachary D. ;

Sings, Heather L. ;

Boparai, Navdeep ;

Burroughs, Margaret ;

Brass, Clifford A. ;

Albrecht, Janice K. ;

Esteban, Rafael .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (13) :1207-1217

[5] Grazoprevir and elbasvir plus ribavirin for chronic HCV genotype-1 infection after failure of combination therapy containing a direct-acting antiviral agent [J].

Forns, Xavier ;

Gordon, Stuart C. ;

Zuckerman, Eli ;

Lawitz, Eric ;

Calleja, Jose L. ;

Hofer, Harald ;

Gilbert, Christopher ;

Palcza, John ;

Howe, Anita Y. M. ;

DiNubile, Mark J. ;

Robertson, Michael N. ;

Wahl, Janice ;

Barr, Eliav ;

Buti, Maria .

JOURNAL OF HEPATOLOGY, 2015, 63 (03) :564-572

[6] Once-Daily Simeprevir (TMC435) With Pegylated Interferon and Ribavirin in Treatment-Naive Genotype 1 Hepatitis C: The Randomized PILLAR Study [J].

Fried, Michael W. ;

Buti, Maria ;

Dore, Gregory J. ;

Flisiak, Robert ;

Ferenci, Peter ;

Jacobson, Ira ;

Marcellin, Patrick ;

Manns, Michael ;

Nikitin, Igor ;

Poordad, Fred ;

Sherman, Morris ;

Zeuzem, Stefan ;

Scott, Jane ;

Gilles, Leen ;

Lenz, Oliver ;

Peeters, Monika ;

Sekar, Vanitha ;

De Smedt, Goedele ;

Beumont-Mauviel, Maria .

HEPATOLOGY, 2013, 58 (06) :1918-1929

[7] Telaprevir for Previously Untreated Chronic Hepatitis C Virus Infection [J].

Jacobson, Ira M. ;

McHutchison, John G. ;

Dusheiko, Geoffrey ;

Di Bisceglie, Adrian M. ;

Reddy, K. Rajender ;

Bzowej, Natalie H. ;

Marcellin, Patrick ;

Muir, Andrew J. ;

Ferenci, Peter ;

Flisiak, Robert ;

George, Jacob ;

Rizzetto, Mario ;

Shouval, Daniel ;

Sola, Ricard ;

Terg, Ruben A. ;

Yoshida, Eric M. ;

Adda, Nathalie ;

Bengtsson, Leif ;

Sankoh, Abdul J. ;

Kieffer, Tara L. ;

George, Shelley ;

Kauffman, Robert S. ;

Zeuzem, Stefan .

NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (25) :2405-2416

[8] Simeprevir plus sofosbuvir, with or without ribavirin, to treat chronic infection with hepatitis C virus genotype 1 in non-responders to pegylated interferon and ribavirin and treatment-naive patients: the COSMOS randomised study [J].

Lawitz, Eric ;

Sulkowski, Mark S. ;

Ghalib, Reem ;

Rodriguez-Torres, Maribel ;

Younossi, Zobair M. ;

Corregidor, Ana ;

DeJesus, Edwin ;

Pearlman, Brian ;

Rabinovitz, Mordechai ;

Gitlin, Norman ;

Lim, Joseph K. ;

Pockros, Paul J. ;

Scott, John D. ;

Fevery, Bart ;

Lambrecht, Tom ;

Ouwerkerk-Mahadevan, Sivi ;

Callewaert, Katleen ;

Symonds, William T. ;

Picchio, Gaston ;

Lindsay, Karen L. ;

Beumont, Maria ;

Jacobson, Ira M. .

LANCET, 2014, 384 (9956) :1756-1765

[9] The Combination of MK-5172, Peginterferon, and Ribavirin Is Effective in Treatment-Naive Patients With Hepatitis C Virus Genotype 1 Infection Without Cirrhosis [J].

Manns, Michael P. ;

Vierling, John M. ;

Bacon, Bruce R. ;

Bruno, Savino ;

Shibolet, Oren ;

Baruch, Yaacov ;

Marcellin, Patrick ;

Caro, Luzelena ;

Howe, Anita Y. M. ;

Fandozzi, Christine ;

Gress, Jacqueline ;

Gilbert, Christopher L. ;

Shaw, Peter M. ;

Cooreman, Michael P. ;

Robertson, Michael N. ;

Hwang, Peggy ;

Dutko, Frank J. ;

Wahl, Janice ;

Mobashery, Niloufar .

GASTROENTEROLOGY, 2014, 147 (02) :366-+

[10]

Mutimer D, 2014, J HEPATOL, V60, P392, DOI 10.1016/j.jhep.2013.11.003

← 1 2 →