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

NCT05467826 | Unknown Phase 4

• 1 other identifier: PKU-HCV-3B
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Hepatitis C; Cirrhosis

Outcome Measures

Primary Outcomes (1)

• The proportion of participants with SVR12

  To evaluate the efficacy of treatment with SOF/VEL plus RBV for 12 weeks or SOF/VEL/VOX for 12 weeks in DAA treatment naïve HCV participants with GT3b, participants initiated on treatment will be assessed for viral load response at 12 weeks post treatment (SVR12). We use the proportion of participants with SVR12 as primary outcome measure.

  12 weeks post treatment.

Secondary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  Treatment start date through treatment completion (up to 24 weeks).

Study Arms (2)

Arm 1

EXPERIMENTAL

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

Drug: Sofosbuvir/Velpatasvir + Ribavirin

Arm 2

EXPERIMENTAL

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

Drug: Sofosbuvir/Velpatasvir/Voxilaprevir

Interventions

Sofosbuvir/Velpatasvir + Ribavirin DRUG

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

Also known as: Epclusa

Arm 1

Sofosbuvir/Velpatasvir/Voxilaprevir DRUG

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

Also known as: Vosevi

Arm 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Liver biopsy showing cirrhosis (e.g., Metavir score = 4 or Ishak score ≥5) in 24 months before screening, or
• Fibroscan® with a result of \>12.5 kPa in 6 months before screening
• 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

You may not qualify if:

• 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
• HBsAg posititve at screening
• Anti-HIV positive at screening
• Alcohol abuse
• Contraindication of ribavirin, including but not limited to hemoglobinapathy
• Pregnant or nursing female or male with pregnant female partner
• Use of any prohibited concomitant medications as described in Section before screening
• Known hypersensitivity to SOF, VEL, RBV or formulation excipients
• 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).
• Assessed as ineligible by investigators

Sponsors & Collaborators

• Peking University People's Hospital: lead

Related Publications (1)

• Huang R, Ji F, Jiang Y, Li S, Su M, Zhong Y, Zu H, Ding Y, Kong X, Shang J, Wei L, Rao H. Sofosbuvir/Velpatasvir/Voxilaprevir Versus Sofosbuvir/Velpatasvir Plus Ribavirin in Patients With Hepatitis C Virus Genotype 3b and Compensated Cirrhosis: A Multicentre Randomized Controlled Trial. J Med Virol. 2025 Nov;97(11):e70709. doi: 10.1002/jmv.70709.

  PMID: 41255102 DERIVED

MeSH Terms

Conditions

Hepatitis C; Fibrosis

Interventions

Sofosbuvir; velpatasvir; Ribavirin; sofosbuvir-velpatasvir drug combination; sofosbuvir velpatasvir voxilaprevir drug combination

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides; Ribonucleosides; Nucleosides

Study Officials

• Huiying Rao, Dr.

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Rui Huang, Dr.

CONTACT

+86 13601208547; strangehead@163.com

Huiying Rao, Dr.

CONTACT

rao.huiying@163.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: July 18, 2022
• First Posted: July 21, 2022
• Study Start: September 1, 2022
• Primary Completion: November 30, 2023
• Study Completion: December 31, 2023
• Last Updated: July 21, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share