Daclatasvir plus asunaprevir in treatment-naïve patients with hepatitis C virus genotype 1b infection.

Aim: To assess daclatasvir plus asunaprevir (DUAL) in treatment-naïve patients from mainland China, Russia and South Korea with hepatitis C virus (HCV) genotype 1b infection.

Methods: Patients were randomly assigned (3:1) to receive 24 wk of treatment with DUAL (daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily) beginning on day 1 of the treatment period (immediate treatment arm) or following 12 wk of matching placebo (placebo-deferred treatment arm). The primary endpoint was a comparison of sustained virologic response at posttreatment week 12 (SVR12) compared with the historical SVR rate for peg-interferon plus ribavirin (70%) among patients in the immediate treatment arm.

Daclatasvir/asunaprevir/beclabuvir, all-oral, fixed-dose combination for patients with chronic hepatitis C virus genotype 1.

Background And Aim: This multinational (Taiwan, South Korea, Russia) phase 3 study evaluated the all-oral, ribavirin-free, fixed-dose combination (DCV-TRIO) of daclatasvir (NS5A inhibitor) 30 mg, asunaprevir (NS3 inhibitor) 200 mg, and beclabuvir (NS5B inhibitor) 75 mg, in patients with chronic hepatitis C virus genotype-1 infection, with or without compensated cirrhosis.

Methods: UNITY-4 (NCT02170727) was an open-label, two-cohort study in which 169 patients, treatment-naive (n = 138) or treatment-experienced (n = 31), received twice-daily DCV-TRIO for 12 weeks with 24 weeks of post-treatment follow-up. The primary efficacy end point was sustained virologic response at post-treatment week 12 (SVR12) in treatment-naive patients.

Daclatasvir and Peginterferon/Ribavirin for Black/African-American and Latino Patients with HCV infection.

Unlabelled:  Background. Patient race and ethnicity have historically impacted HCV treatment response. This phase 3 study evaluated daclatasvir with peginterferon-alfa-2a/ribavirin (pegIFN alfa-2a/RBV) in treatment-naive black/African American (AA), Latino, and white non-Latino patients with chronic HCV genotype 1 infection.

A phase 3, open-label study of daclatasvir plus asunaprevir in Asian patients with chronic hepatitis C virus genotype 1b infection who are ineligible for or intolerant to interferon alfa therapies with or without ribavirin.

Background And Aim: Daclatasvir plus asunaprevir has demonstrated efficacy and safety in patients with chronic hepatitis C virus genotype 1b infection. This study focused on evaluating daclatasvir plus asunaprevir in interferon (±ribavirin)-ineligible or -intolerant Asian patients with genotype 1b infection from mainland China, Korea, and Taiwan.

Methods: Interferon (±ribavirin)-ineligible and -intolerant patients with genotype 1b infection received daclatasvir 60 mg tablets once daily plus asunaprevir 100 mg soft capsules twice daily for 24 weeks.

Randomized controlled trial of the NS5A inhibitor daclatasvir plus pegylated interferon and ribavirin for HCV genotype-4 (COMMAND-4).

Background: Treatment options for HCV genotype-4 (GT4) are limited. This Phase III study (COMMAND-4; AI444-042) evaluated the efficacy and safety of daclatasvir (DCV), a pan-genotypic HCV NS5A inhibitor, with pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in treatment-naive patients with HCV GT4 infection.

Methods: Patients were randomly assigned (2:1; blinded) to treatment with DCV 60 mg (n=82) or placebo (n=42) once daily plus PEG-IFN 180 µg weekly and RBV 1,000-1,200 mg/day (weight-based) twice daily.

Boceprevir for chronic HCV genotype 1 infection in patients with prior treatment failure to peginterferon/ribavirin, including prior null response.

Background & Aims: Boceprevir with peginterferon/ribavirin (BOC/PR) leads to significantly higher sustained virological response (SVR) rates in patients with chronic hepatitis C and partial response or relapse after prior treatment with peginterferon/ribavirin. We studied the efficacy of BOC/PR in patients with prior treatment failure, including those with a null response (<2-log10 decline in HCV RNA), to peginterferon/ribavirin.

Methods: Patients in the control arms of boceprevir Phase 2/3 studies who did not achieve SVR were re-treated with BOC/PR for up to 44 weeks.

Antiviral activity of boceprevir monotherapy in treatment-naive subjects with chronic hepatitis C genotype 2/3.

Background & Aims: To examine the antiviral activity of boceprevir, a hepatitis C virus (HCV) protease inhibitor, in HCV genotype (G) 2/3-infected patients.

Methods: We assessed boceprevir and telaprevir activity against an HCV G2 and G3 isolates enzyme panel, in replicon, and in phenotypic cell-based assays. Additionally, a phase I study evaluated the antiviral activity of boceprevir monotherapy (200mg BID, 400mg BID, or 400mg TID) vs.

Pharmacokinetic interactions between the hepatitis C virus protease inhibitor boceprevir and ritonavir-boosted HIV-1 protease inhibitors atazanavir, darunavir, and lopinavir.

Background: Boceprevir represents a new treatment option for hepatitis C (HCV)-infected patients, including those with HCV/human immunodeficiency virus coinfection; however, little is known about pharmacokinetic interactions between boceprevir and antiretroviral drugs.

Methods: A randomized, open-label study to assess the pharmacokinetic interactions between boceprevir and ritonavir-boosted protease inhibitors (PI/r) was conducted in 39 healthy adults. Subjects received boceprevir (800 mg, 3 times daily) for 6 days and then received PI/r as follows: atazanavir (ATV) 300 mg once daily, lopinavir (LPV) 400 mg twice daily, or darunavir (DRV) 600 mg twice daily, each with ritonavir (RTV) 100 mg on days 10-31, plus concomitant boceprevir on days 25-31.

Single-dose pharmacokinetics of boceprevir in subjects with impaired hepatic or renal function.

Background And Objective: Boceprevir is a novel inhibitor of the hepatitis C virus NS3 protease and was recently approved for the treatment of patients with chronic hepatitis C infection. The objective of this study was to evaluate the impact of impaired hepatic or renal function on boceprevir pharmacokinetics and safety/tolerability.

Methods: We conducted two open-label, single-dose, parallel-group studies comparing the safety and pharmacokinetics of boceprevir in patients with varying degrees of hepatic impairment compared with healthy controls in one study and patients with end-stage renal disease (ESRD) on haemodialysis with healthy controls in the other.

Antiviral activity of narlaprevir combined with ritonavir and pegylated interferon in chronic hepatitis C patients.

Unlabelled: Narlaprevir (SCH 900518) is a potent inhibitor of the hepatitis C virus (HCV) nonstructural protein 3 serine protease that is primarily metabolized by the cytochrome P450-3A4 system. In order to explore the use of ritonavir-based pharmacokinetic enhancement of an HCV protease inhibitor, this study investigated the safety, tolerability, pharmacokinetics, and antiviral activity of narlaprevir (with or without ritonavir) administered as monotherapy and as combination therapy with pegylated interferon-α-2b (PEG-IFN-α-2b) to HCV genotype 1-infected patients. This was a randomized, placebo-controlled, two-period, blinded study in 40 HCV genotype 1-infected patients (naïve and treatment-experienced).

Short-term administration of the CCR5 antagonist vicriviroc to patients with HIV and HCV coinfection is safe and tolerable.

Objective: CCR5 antagonists block HIV cell entry through competitive binding to the CCR5 receptor present on the surface of CD4(+) cells. The CCR5 receptor is also present on CD8(+) cells involved in clearing hepatitis C virus (HCV). The goal of the present study was to examine the short-term safety of a CCR5 antagonist, vicriviroc, in patients with HIV/HCV coinfection.