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Direct-acting antiviral agents (DAAs) targeting HCV have revolutionized the treatment of HCV. The efficacy of DAA-based therapy can depend on patient-related factors such as treatment experience, cirrhosis, but also on viral genotype. The high prevalence of genotype 3, which is considered difficult to cure, remains a challenge because many oral DAAs are less effective for this genotype, particularly subtype 3b than for others. Current guidance generally recommends sofosbuvir (SOF)/velpatasvir (VEL) ± ribavirin (RBV), glecaprevir/pibrentasvir and SOF/VEL/voxilaprevir (VOX) as first-line therapy for genotype 3, and an interferon-based regimen - SOF plus pegylated interferon and ribavirin is still recommended as an alternative treatment option. These recommendations are based on clinical data generated in regions where genotype 3a predominates. Our recent study indicated that sofosbuvir plus ribavirin for 24 weeks in subjects with HCV genotype 3 infection resulted in high rates of SVR. However, the SVR12 rate among subjects with genotype 3b was lower than that observed in subjects with genotype 3a infection, particularly among treatment-experienced subjects with cirrhosis.
Our study aimed to investigate the efficacy and safety of SOF/VEL plus RBV for 12 weeks or SOF/VEL/VOX for 12 weeks in DAAs treatment naïve HCV subjects with GT3b, compensated cirrhosis in China.
Full description
Chronic hepatitis C virus (HCV) infection, which may lead to cirrhosis and hepatocellular carcinoma, is a major cause of chronic liver disease worldwide. Genotype 3 is the second most common genotype globally, accounting for approximately 18% of all adult HCV infections. Subjects with HCV genotype 3 infection, particularly genotype 3b, have a greater risk of developing hepatic steatosis, more rapid progression of hepatic fibrosis and cirrhosis, and hepatocellular carcinoma. Although there is only a small percentage of HCV subjects with genotype 3 in East Asia (5.4%) and China (8.7%), genotype 3b represents more than 50% of genotype 3 subjects in China,compared to most other regions of the world where genotype 3a predominates. In certain provinces of China, such as Yunnan Guizhou, and Chongqing, genotype 3b is the predominant HCV subtype among genotype 3 subjects.
Direct-acting antiviral agents (DAAs) targeting HCV have revolutionized the treatment of HCV. The efficacy of DAA-based therapy can depend on patient-related factors such as treatment experience, cirrhosis, but also on viral genotype. The high prevalence of genotype 3, which is considered difficult to cure, remains a challenge because many oral DAAs are less effective for this genotype, particularly subtype 3b than for others. Current guidance generally recommends sofosbuvir (SOF)/velpatasvir (VEL) ± ribavirin (RBV), glecaprevir/pibrentasvir and SOF/VEL/voxilaprevir (VOX) as first-line therapy for genotype 3, and an interferon-based regimen - SOF plus pegylated interferon and ribavirin is still recommended as an alternative treatment option. These recommendations are based on clinical data generated in regions where genotype 3a predominates. Our recent study indicated that sofosbuvir plus ribavirin for 24 weeks in subjects with HCV genotype 3 infection resulted in high rates of SVR. However, the SVR12 rate among subjects with genotype 3b was lower than that observed in subjects with genotype 3a infection, particularly among treatment-experienced subjects with cirrhosis.
Our study aimed to investigate the efficacy and safety of SOF/VEL plus RBV for 12 weeks or SOF/VEL/VOX for 12 weeks in DAAs treatment naïve HCV subjects with GT3b, compensated cirrhosis in China.
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Inclusion criteria
Willing and able to provide written informed consent
Male or female, age ≥18 years
Body mass index (BMI) between 18.0-35.0kg/m2 and bodyweight ≥ 40 kg
Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy
Anti-HCV positive at screening
HCV RNA 104 IU/mL at screening by the Central Laboratory
HCV genotype 3b assessed at screening by the Central Laboratory
DAA treatment naïve defined as having never been exposed to approved or experimental HCV-specific direct-acting antiviral agents. Pegylated interferon/interferon based prior treatment is allowed.
Cirrhosis Determination: cirrhosis is defined as any one of the following:
The lab test at screening should meet all the criterion below: a) ALT ≤ 10 the upper limit of normal (ULN); b) AST ≤ 10 ULN; c) Total bilirubin ≤ 2 ULN; d) Platelets ≥ 60,000/L; e) Neutrophile ≥ 1,500/L; f) HbA1c ≤ 8.5%; g) Creatinine clearance (CLcr) ≥ 60 mL /min as calculated by the Cockcroft-Gault equation; h) Hemoglobin ≥ 11 g/dL for female subjects; ≥ 12 g/dL for male subjects; i) Albumin ≥ 3 g/dL; j) INR ≤ 1.7 x ULN; k) AFP <100ng/mL;if 20ng/mL≤AFP≤100ng/mL,HCC should be exclude by liver ultrasound
Females of childbearing potential must have a negative serum pregnancy test at screening
Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
Male subjects must agree to avoid donating sperm in 6 months after the last dose of drug
Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator
Subject must be able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments
Exclusion criteria
Primary purpose
Allocation
Interventional model
Masking
100 participants in 2 patient groups
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Central trial contact
Huiying Rao, Dr.; Rui Huang, Dr.
Data sourced from clinicaltrials.gov
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