Efficacy and Safety of SOF/VEL + RBV and SOF/VEL/VOX for 12 Weeks in HCV Subjects With GT3b and Compensated Cirrhosis

NCT ID: NCT05467826

Last Updated: 2022-07-21

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2023-12-31

Brief Summary

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.

Detailed 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.

Conditions

Hepatitis C; Cirrhosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Sofosbuvir 400mg/velpatasvir 100mg + ribavirin 1000mg/1200mg for 12 weeks

Group Type: EXPERIMENTAL

Sofosbuvir/Velpatasvir + Ribavirin

Intervention Type: DRUG

Sofosbuvir 400mg/velpatasvir 100mg + ribavirin 1000mg/1200mg for 12 weeks

Arm 2

Sofosbuvir 400mg/velpatasvir 100mg/voxilaprevir 100mg for 12 weeks

Group Type: EXPERIMENTAL

Sofosbuvir/Velpatasvir/Voxilaprevir

Intervention Type: DRUG

Sofosbuvir 400mg/velpatasvir 100mg/voxilaprevir 100mg for 12 weeks

Interventions

Sofosbuvir/Velpatasvir + Ribavirin

Sofosbuvir 400mg/velpatasvir 100mg + ribavirin 1000mg/1200mg for 12 weeks

Intervention Type: DRUG

Sofosbuvir/Velpatasvir/Voxilaprevir

Sofosbuvir 400mg/velpatasvir 100mg/voxilaprevir 100mg for 12 weeks

Intervention Type: DRUG

Other Intervention Names

Epclusa; Vosevi

Eligibility Criteria

Inclusion Criteria

1. Willing and able to provide written informed consent

2. Male or female, age ≥18 years

3. Body mass index (BMI) between 18.0-35.0kg/m2 and bodyweight ≥ 40 kg

4. Chronic HCV infection (≥ 6 months) documented by prior medical history or liver biopsy

5. Anti-HCV positive at screening

6. HCV RNA 104 IU/mL at screening by the Central Laboratory

7. HCV genotype 3b assessed at screening by the Central Laboratory

8. 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.

9. Cirrhosis Determination: cirrhosis is defined as any one of the following:

1. Liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score ≥5) in 24 months before screening, or

2. Fibroscan® with a result of >12.5 kPa in 6 months before screening

10. 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

11. Females of childbearing potential must have a negative serum pregnancy test at screening

12. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception

13. Male subjects must agree to avoid donating sperm in 6 months after the last dose of drug

14. Subject must be of generally good health, with the exception of chronic HCV infection, as determined by the Investigator

15. 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

1. Decompensated cirrhosis, including but not limited to: prior or current ascites, variceal hemorrhage and/or hepatic encephalopathy; prior or current Child-Pugh B or C

2. HBsAg posititve at screening

3. Anti-HIV positive at screening

4. Alcohol abuse

5. Contraindication of ribavirin, including but not limited to hemoglobinapathy

6. Pregnant or nursing female or male with pregnant female partner

7. Use of any prohibited concomitant medications as described in Section before screening

8. Known hypersensitivity to SOF, VEL, RBV or formulation excipients

9. Subjects who has any of the following history: a) Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, cholangitis); b) Solid organ transplantation; c) Significant pulmonary disease, significant cardiac disease or porphyria; d) Pancreatitis; e) Autoimmune diseases (e.g., systemic lupus erythematosus, sarcoidosis, psoriasis); f) Psychiatric hospitalization, suicide attempt, and/or a period of disability as a result of their psychiatric illness within the last 5 years; g) Malignancy within the 5 years prior to screening, with the exception of specific cancers that have been cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible; h) Significant drug allergy (such as anaphylaxis or hepatotoxicity).

10. Assessed as ineligible by investigators

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University People's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Huiying Rao

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Huiying Rao, Dr.

Role: PRINCIPAL_INVESTIGATOR

Peking University People's Hospital

Central Contacts

Rui Huang, Dr.

Role: CONTACT

strangehead@163.com

+86 13601208547

Huiying Rao, Dr.

Role: CONTACT

rao.huiying@163.com

Other Identifiers

PKU-HCV-3B

Identifier Type: -

Identifier Source: org_study_id