Related Experiment Video
Updated: Mar 13, 2026
A Cell Culture Model for Producing High Titer Hepatitis E Virus Stocks
Published on: June 26, 2020
Effectiveness of Elbasvir and Grazoprevir Combination, With or Without Ribavirin, for Treatment-Experienced Patients
Paul Kwo1, Edward J Gane2, Cheng-Yuan Peng3
1Indiana University, Indianapolis, Indiana.
Insights
This study shows that elbasvir and grazoprevir, with or without ribavirin, effectively treats difficult-to-cure hepatitis C virus (HCV) genotypes 1, 4, or 6. High sustained virologic response rates were achieved in patients previously treated with peg-interferon and ribavirin.
Area of Science:
- Hepatology
- Virology
- Pharmacology
Background:
- Hepatitis C virus (HCV) genotypes 1, 4, and 6 in patients previously treated with peg-interferon and ribavirin present a significant therapeutic challenge, particularly those with cirrhosis or prior treatment failure.
- Elbasvir (HCV NS5A inhibitor) and grazoprevir (HCV NS3/4A protease inhibitor) are potent antiviral agents investigated for HCV treatment.
Purpose of the Study:
- To evaluate the efficacy and safety of a fixed-dose combination of elbasvir and grazoprevir, with or without ribavirin, in patients with treatment-experienced HCV genotypes 1, 4, or 6.
- To determine the sustained virologic response rate (SVR12) at 12 or 16 weeks of treatment in this challenging patient population.
Main Methods:
- A phase 3, randomized, controlled, open-label trial involving 420 patients across 65 centers in 15 countries.
- Patients received elbasvir (50 mg) and grazoprevir (100 mg) once daily, with or without ribavirin twice daily, for 12 or 16 weeks.
- Randomization was stratified by cirrhosis status and treatment failure type; SVR12 was the primary endpoint.
Main Results:
- SVR12 rates ranged from 92.4% to 98.1% across treatment arms. Specifically, 12-week treatment yielded 92.4% (elbasvir/grazoprevir) and 94.2% (elbasvir/grazoprevir + ribavirin). 16-week treatment yielded 92.4% (elbasvir/grazoprevir) and 98.1% (elbasvir/grazoprevir + ribavirin).
- Virologic failure was low, particularly in the 16-week arm with ribavirin (0%). Higher failure rates were observed in the 12-week arm without ribavirin for specific genotypes and treatment failure types.
- Common adverse events included fatigue (23.1%), headache (19.8%), and nausea (11.0%), indicating good tolerability.
Conclusions:
- The elbasvir and grazoprevir combination tablet, with or without ribavirin, demonstrates high efficacy in achieving SVR12 in patients with previously treated HCV genotypes 1, 4, or 6, including those with cirrhosis or null response.
- The treatment regimen was generally well-tolerated, supporting its use in this difficult-to-treat population.
- ClinicalTrials.gov Identifier: NCT02105701.
Background & Aims:
Patients infected with hepatitis C virus (HCV) genotype 1, 4, or 6, with or without cirrhosis, previously treated with peg-interferon and ribavirin, are a challenge to treat. We performed a phase 3 randomized controlled open-label trial to assess the effects of 12 or 16 weeks of treatment with once-daily elbasvir (an HCV NS5A inhibitor, 50 mg) and grazoprevir (an HCV NS3/4A protease inhibitor, 100 mg), in a fixed-dose combination tablet, with or without twice-daily ribavirin, in this patient population.
Methods:
We analyzed data from 420 patients (35% with cirrhosis, 64% with a null or partial response to peg-interferon and ribavirin) who were randomly assigned (1:1:1:1) to groups given elbasvir and grazoprevir once daily, with or without twice-daily ribavirin, for 12 or 16 weeks, at 65 study centers in 15 countries in Europe, Asia, and Central and North America. Randomization was stratified by cirrhosis status and type of peg-interferon and ribavirin treatment failure. HCV RNA was measured using COBAS TaqMan v2.0. The primary end point was HCV RNA <15 IU/mL, 12 weeks after completion of treatment (SVR12). We aimed to determine whether the proportion of patients achieving an SVR12 in any group was greater than the reference rate (58%).
Results:
With 12 weeks of treatment, an SVR12 was achieved by 92.4% of patients given elbasvir and grazoprevir and 94.2% of patients given elbasvir and grazoprevir with ribavirin. With 16 weeks of treatment, an SVR12 was achieved by 92.4% of patients given elbasvir and grazoprevir and 98.1% of patients given elbasvir and grazoprevir with ribavirin. Among patients treated for 12 weeks without ribavirin, virologic failure occurred in 6.8%, 0%, and 12.5% of patients with HCV genotype 1a, 1b, or 4 infection, respectively. Among patients given elbasvir and grazoprevir for 12 weeks, virologic failure occurred in 0% of patients infected with HCV genotypes 1 and 4 who relapsed after completing peg-interferon and ribavirin, and 7.5% infected with HCV genotypes 1 and 4, respectively, with a null or partial response to peg-interferon and ribavirin. Among patients treated for 16 weeks who received ribavirin, there were no incidences of virologic failure. Common adverse events were fatigue (23.1%), headache (19.8%), and nausea (11.0%).
Conclusions:
The combination tablet of elbasvir and grazoprevir, with or without ribavirin, was highly efficacious in inducing an SVR12 in patients with HCV genotype 1, 4, or 6 infection failed by previous treatment with peg-interferon and ribavirin, including patients with cirrhosis and/or a prior null response. The treatment was generally well tolerated. ClinicalTrials.gov Number: NCT02105701.
More Related Videos
Related Concept Videos
01:08Effect of Hepatic Disease on Pharmacokinetics: Dose Adjustments Due to Hepatic Impairment
01:29Chronic Pancreatitis II: Collaborative Care
Assessment:
01:29Drugs for Treatment of Ulcerative Colitis in IBD
01:16Hepatic Drug Excretion: Influencing Factors
01:22Effect of Hepatic Disease on Pharmacokinetics: Pathophysiologic Assessment and Liver Function Test
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...