Journal ArticleDOI
Grazoprevir–Elbasvir Combination Therapy for Treatment-Naive Cirrhotic and Noncirrhotic Patients With Chronic Hepatitis C Virus Genotype 1, 4, or 6 Infection: A Randomized Trial
Stefan Zeuzem,Reem Ghalib,K. Rajender Reddy,Paul J. Pockros,Ziv Ben Ari,Yue Zhao,Deborah D. Brown,Shuyan Wan,Mark J. DiNubile,Bach-Yen Nguyen,Michael N. Robertson,Janice Wahl,Eliav Barr,Joan R. Butterton +13 more
TLDR
Grazoprevir and elbasvir were evaluated in a randomized, blinded, placebo-controlled trial in treatment-naive patients with hepatitis C virus (HCV) infection.Abstract:
BACKGROUND Novel interferon- and ribavirin-free regimens are needed to treat hepatitis C virus (HCV) infection. OBJECTIVE To evaluate the safety and efficacy of grazoprevir (NS3/4A protease inhibitor) and elbasvir (NS5A inhibitor) in treatment-naive patients. DESIGN Randomized, blinded, placebo-controlled trial. (ClinicalTrials.gov: NCT02105467). SETTING 60 centers in the United States, Europe, Australia, Scandinavia, and Asia. PATIENTS Cirrhotic and noncirrhotic treatment-naive adults with genotype 1, 4, or 6 infection. INTERVENTION Oral, once-daily, fixed-dose grazoprevir 100 mg/elbasvir 50 mg for 12 weeks, stratified by fibrosis and genotype. Patients were randomly assigned 3:1 to immediate or deferred therapy. MEASUREMENTS Proportion of patients in the immediate-treatment group achieving unquantifiable HCV RNA 12 weeks after treatment (SVR12); adverse events in both groups. RESULTS Among 421 participants, 194 (46%) were women, 157 (37%) were nonwhite, 382 (91%) had genotype 1 infection, and 92 (22%) had cirrhosis. Of 316 patients receiving immediate treatment, 299 of 316 (95% [95% CI, 92% to 97%]) achieved SVR12, including 144 of 157 (92% [CI, 86% to 96%]) with genotype 1a, 129 of 131 (99% [CI, 95% to 100%]) with genotype 1b, 18 of 18 (100% [CI, 82% to 100%]) with genotype 4, 8 of 10 (80% [CI, 44% to 98%]) with genotype 6, 68 of 70 (97% [CI, 90% to 100%]) with cirrhosis, and 231 of 246 (94% [CI, 90% to 97%]) without cirrhosis. Virologic failure occurred in 13 patients (4%), including 1 case of breakthrough infection and 12 relapses, and was associated with baseline NS5A polymorphisms and emergent NS3 or NS5A variants or both. Serious adverse events occurred in 9 (2.8%) and 3 (2.9%) patients in the active and placebo groups, respectively (difference <0.05 percentage point [CI, -5.4 to 3.1 percentage points]); none were considered drug related. The most common adverse events in the active group were headache (17%), fatigue (16%), and nausea (9%). LIMITATION The study lacked an active-comparator control group and included relatively few genotype 4 and 6 infections. CONCLUSION Grazoprevir-elbasvir achieved high SVR12 rates in treatment-naive cirrhotic and noncirrhotic patients with genotype 1, 4, or 6 infection. This once-daily, all-oral, fixed-combination regimen represents a potent new therapeutic option for chronic HCV infection. PRIMARY FUNDING SOURCE Merck & Co.read more
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Ombitasvir/paritaprevir/ritonavir plus ribavirin for 24 weeks in patients with HCV GT4 and compensated cirrhosis (AGATE-I Part II).
Tarik Asselah,Negar N. Alami,Christophe Moreno,Stanislas Pol,Stanislas Pol,Stylianos Karatapanis,Michael Gschwantler,Yves Horsmans,Ioannis S. Elefsiniotis,Dominique Larrey,Carlo Ferrari,Mario Rizzetto,Alessandra Orlandini,Jose Luis Calleja,Savino Bruno,Gretja Schnell,Roula B. Qaqish,Rebecca Redman,Tami Pilot-Matias,Sarah Kopecky-Bromberg,Yao Yu,N. Mobashery +21 more
TL;DR: The trial was extended to include a 24‐week treatment arm to fully assess treatment duration in patients with chronic hepatitis C genotype 4 infection and compensated cirrhosis.
Journal ArticleDOI
Pharmacokinetics of elbasvir and grazoprevir in subjects with end-stage renal disease or severe renal impairment.
Luzelena Caro,Larissa Wenning,Hwa-Ping Feng,Zifang Guo,Lihong Du,Pratik Bhagunde,Christine Fandozzi,Deborah Panebianco,William L. Marshall,Joan R. Butterton,Marian Iwamoto,Wendy W. Yeh +11 more
TL;DR: The phase 1 and population pharmacokinetic investigations that support dosing recommendations for elbasvir/grazoprevir (EBR/GZR) in hepatitis C virus-infected people with advanced chronic kidney disease and those with ESRD are described.
Journal ArticleDOI
Consenso Mexicano para el Tratamiento de la Hepatitis C
I. Aiza-Haddad,A. Ballesteros-Amozurrutia,Omar D. Borjas-Almaguer,M. Castillo-Barradas,G.E. Castro-Narro,Norberto C. Chávez-Tapia,R.A. Chirino-Sprung,L.E. Cisneros-Garza,Margarita Dehesa-Violante,Judith Flores-Calderón,A. Flores-Gaxiola,Ignacio García-Juárez,M.S. González-Huezo,Emmanuel I. Gonzalez-Moreno,F. Higuera-de la Tijera,D. Kershenobich-Stalnikowitz,E. López-Méndez,R. Malé-Velázquez,E.R. Marín-López,J.A. Mata-Marín,Nahum Méndez-Sánchez,Roberto Monreal-Robles,R. Moreno-Alcántar,Linda E. Muñoz-Espinosa,S. Navarro-Alvarez,N. Pavia-Ruz,A.M. Pérez-Ríos,J.L. Poo-Ramírez,M.T. Rizo-Robles,Juan Francisco Sánchez-Ávila,R. Sandoval-Salas,Aldo Torre,R. Torres-Ibarra,R. Trejo-Estrada,J.A. Velarde-Ruiz Velasco,E. Wolpert-Barraza,Francisco Bosques-Padilla +36 more
TL;DR: Esta guia busca dar recomendaciones con enfasis en los nuevos antivirales de accion directa y de esta manera facilitar su uso en the practica clinica.
Journal ArticleDOI
No Pharmacokinetic Interactions Between Elbasvir or Grazoprevir and Methadone in Participants Receiving Maintenance Opioid Agonist Therapy.
Hwa-Ping Feng,Zifang Guo,Luzelena Caro,William L. Marshall,William L. Marshall,Fang Liu,Deborah Panebianco,Pavan Vaddady,Christina Reitmann,Patricia Jumes,Dennis Wolford,Iain Fraser,Iain Fraser,Robert Valesky,Monika Martinho,Joan R. Butterton,Marian Iwamoto,Lynn Webster,Wendy W. Yeh +18 more
TL;DR: It is indicated that no dose adjustment is required for individuals with HCV infection receiving stable methadone therapy and the EBR/GZR fixed‐dose regimen.
Journal ArticleDOI
Treatment of Chronic HCV Genotype 1 Coinfection
TL;DR: HCV treatment in HIV-coinfected patients is the same as in HCV-monoinfected patients as response rates under DAA in the setting of HIV coinfection have been as good as inHCV-Mono Infected patients.
References
More filters
Journal ArticleDOI
The use of confidence or fiducial limits illustrated in the case of the binomial
C. J. Clopper,E. S. Pearson +1 more
Journal ArticleDOI
Sofosbuvir for previously untreated chronic hepatitis C infection
Eric Lawitz,Alessandra Mangia,David L. Wyles,Maribel Rodriguez-Torres,Tarek Hassanein,Stuart C. Gordon,Michael Schultz,M. Davis,Zeid Kayali,K. Rajender Reddy,Ira M. Jacobson,Kris V. Kowdley,L. Nyberg,G. Mani Subramanian,Robert H. Hyland,Sarah Arterburn,Deyuan Jiang,John McNally,Diana M. Brainard,William T. Symonds,John G. McHutchison,Aasim Sheikh,Zobair M. Younossi,Edward Gane +23 more
TL;DR: In a single-group study of sofosbuvir combined with peginterferon-ribavirin, patients with predominantly genotype 1 or 4 HCV infection had a rate of sustained virologic response of 90% at 12 weeks.
Journal ArticleDOI
Ledipasvir and Sofosbuvir for Untreated HCV Genotype 1 Infection
Nezam H. Afdhal,Stefan Zeuzem,Paul Y. Kwo,Mario Chojkier,Norman Gitlin,Massimo Puoti,Manuel Romero-Gómez,Jean-Pierre Zarski,Kosh Agarwal,Peter Buggisch,Graham R. Foster,Norbert Bräu,Maria Buti,Ira M. Jacobson,G. Mani Subramanian,Xiao Ding,Hongmei Mo,Jenny C. Yang,Phillip S. Pang,William T. Symonds,John G. McHutchison,Andrew J. Muir,Alessandra Mangia,Patrick Marcellin +23 more
TL;DR: Once-daily ledipasvir-sofosbuvir with or without ribavirin for 12 or 24 weeks was highly effective in previously untreated patients with HCV genotype 1 infection.
Journal ArticleDOI
Ledipasvir and sofosbuvir for 8 or 12 weeks for chronic HCV without cirrhosis
Kris V. Kowdley,Stuart C. Gordon,K. Rajender Reddy,Lorenzo Rossaro,David E. Bernstein,Eric Lawitz,Mitchell L. Shiffman,Eugene R. Schiff,Reem Ghalib,Michael J. Ryan,Vinod K. Rustgi,Mario Chojkier,Robert Herring,Adrian M. Di Bisceglie,Paul J. Pockros,G. Mani Subramanian,Di An,Evguenia S. Svarovskaia,Robert H. Hyland,Phillip S. Pang,William T. Symonds,John G. McHutchison,Andrew J. Muir,David Pound,Michael W. Fried +24 more
TL;DR: Leadipasvir-sofosbuvir for 8 weeks was associated with a high rate of sustained virologic response among previously untreated patients with HCV genotype 1 infection without cirrhosis, and results indicated noninferiority of the 8-week ledipas Viral-SofosBuvir regimen.
Journal ArticleDOI
Treatment of HCV with ABT-450/r-ombitasvir and dasabuvir with ribavirin.
Jordan J. Feld,Kris V. Kowdley,Eoin Coakley,Samuel H. Sigal,David R. Nelson,Darrell H. G. Crawford,Ola Weiland,Humberto Aguilar,Junyuan Xiong,Tami Pilot-Matias,Barbara DaSilva-Tillmann,Lois Larsen,Thomas Podsadecki,B. Bernstein +13 more
TL;DR: In previously untreated patients with HCV genotype 1 infection and no cirrhosis, a 12-week multitargeted regimen of ABT-450/r-ombitasvir and dasabuvir with ribavirin was highly effective and was associated with a low rate of treatment discontinuation.
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