Ombitasvir plus paritaprevir plus ritonavir with or without ribavirin in treatment-naive and treatment-experienced patients with genotype 4 chronic hepatitis C virus infection (PEARL-I): a randomised, open-label trial

Fecha de publicación: 20/06/2015

Autores de IIS La Fe

Marina Berenguer Haym

Autor

Participantes ajenos a IIS La Fe

Hézode C
Asselah T
Reddy KR
Hassanein T
Fleischer-Stepniewska K
Marcellin P
Hall C
Schnell G
Pilot-Matias T
Mobashery N
Redman R
Vilchez RA
Pol S

Grupos

Hepatología, Cirugia Hepatobiliopancreática y Trasplantes

Leader

Marina Berenguer Haym

Abstract

Background Hepatitis C virus (HCV) genotype 4 accounts for about 13% of global HCV infections. Because interferon-containing treatments for genotype 4 infection have low efficacy and poor tolerability, an unmet need exists for effective all-oral regimens. We examined the efficacy and safety of an all-oral interferon-free regimen of ombitasvir, an NS5A inhibitor, and paritaprevir (ABT-450), an NS3/4A protease inhibitor dosed with ritonavir (ombitasvir plus paritaprevir plus ritonavir), given with or without ribavirin. Methods In this multicentre ongoing phase 2b, randomised, open-label combination trial (PEARL-I), patients were recruited from academic, public, and private hospitals and clinics in France, Hungary, Italy, Poland, Romania, Spain, Turkey, and the USA. Eligible participants were aged 18-70 years with non-cirrhotic, chronic HCV genotype 4 infection (documented >= 6 months before screening) and plasma HCV RNA levels higher than 10 000 IU/mL. Previously untreated (treatment-naive) patients were randomly assigned (1: 1) by computer-generated randomisation lists to receive once-daily ombitasvir (25 mg) plus paritaprevir (150 mg) plus ritonavir (100 mg) with or without weight-based ribavirin for 12 weeks. Previously treated (treatment-experienced) patients who had received pegylated interferon plus ribavirin all received the ribavirin-containing regimen. The primary endpoint was a sustained virological response (HCV RNA <25 IU/mL) 12 weeks after the end of treatment (SVR 12). Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01685203. Findings Between Aug 14, 2012, and Nov 19, 2013, 467 patients with HCV infection were screened, of whom 174 were infected with genotype 4. 135 patients were randomly assigned to treatment and received at least one dose of study medication; 86 patients were treatment-naive, of whom 44 received ombitasvir plus paritaprevir plus ritonavir and 42 received ombitasvir plus paritaprevir plus ritonavir with ribavirin, and 49 treatment-experienced patients received the ribavirin-containing regimen. In previously untreated patients, SVR 12 rates were 100% (42/42 [95% CI 91.6-100]) in the ribavirin-containing regimen and 90.9% (40/44 [95% CI 78.3-97.5]) in the ribavirin-free regimen. No statistically signifi cant differences in SVR 12 rates were noted between the treatment-naive groups (mean difference -9.16% [95% CI -1961 to 1.29]; p=0.086). All treatment-experienced patients achieved SVR 12 (49/49; 100% [95% CI 92.7-100]). In the ribavirin-free group, two (5%) of 42 treatment-naive patients had virological relapse, and one (2%) of 44 had virological breakthrough; no virological failures were recorded in the ribavirin-containing regimen. The most common adverse event was headache (14 [29%] of 49 treatment-experienced patients and 14 [33%] of 42 treatment-naive patients). No adverse event-related discontinuations or dose interruptions of study medications, including ribavirin, were noted, and only four patients (4%) of 91 receiving ribavirin required dose modification for haemoglobin less than 100 g/L or anaemia. Interpretation An interferon-free regimen of ombitasvir plus paritaprevir plus ritonavir with or without ribavirin achieved high sustained virological response rates at 12 weeks after the end of treatment and was generally well tolerated, with low rates of anaemia and treatment discontinuation in non-cirrhotic previously untreated and previously treated patients with HCV genotype 4 infection.

Datos de la publicación

ISSN/ISSNe:: 0140-6736, 1474-547X
Tipo:: Article
Páginas:: 2502-2509
DOI:: 10.1016/S0140-6736(15)60159-3
PubMed:: 25837829
Factor de Impacto:: 14,974 SCImago ℠
Cuartil:: Q1 SCImago ℠

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Filiaciones

Hézode C:: Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, Université Paris-Est, Inserm, Créteil, France.
Asselah T:: Centre de Recherche sur l'Inflammation (CRI), Inserm UMR, Université Paris Diderot, Service d'Hépatologie, AP-HP Hôpital Beaujon, Clichy, France
Reddy KR:: Division of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, PA, USA
Hassanein T:: Southern California Liver Centers and Southern California Research Center, Coronado, CA, USA
Berenguer M:: Hepatology Unit, Hospital Universitario La Fe, Universidad de Valencia and Ciberehd, Valencia, Spain
Fleischer-Stepniewska K:: Department of Infectious Disease, Liver Diseases and Acquired Immune Deficiencies, Wroclaw Medical University, Wroclaw, Poland
Marcellin P:: Service d'Hépatologie, AP-HP Hôpital Beaujon, Clichy, France
Hall C:: AbbVie Inc, North Chicago, IL, USA
Schnell G:: AbbVie Inc, North Chicago, IL, USA
Pilot-Matias T:: AbbVie Inc, North Chicago, IL, USA
Mobashery N:: AbbVie Inc, North Chicago, IL, USA
Redman R:: AbbVie Inc, North Chicago, IL, USA
Vilchez RA:: AbbVie Inc, North Chicago, IL, USA
Pol S:: Groupe Hospitalier Cochin-Saint Vincent De Paul, Université Paris Descartes, Inserm, Institut Pasteur, Paris, France