Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) for Patients With Hepatitis C Virus Infection

Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) for Patients With Hepatitis C Virus Infection: Real-world Effectiveness and Safety in Taiwan

The investigators aim to assess the effectiveness and safety of sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) for 12 weeks in hepatitis C virus (HCV)-infected patients who fail to prior NS5A-containing DAA regimens and HCV genotype 1a and 3 patients who fail to prior non-NS5A-containing DAA regimen in Taiwan on a basis of a multicenter observational study.

Study Overview

• Status: Recruiting
• Conditions: Hepatitis C Virus Infection; Treatment Side Effects; Effect of Drug; Adherence, Treatment
• Intervention / Treatment: Drug: Vosevi 400/100/100 Oral Tablet

Detailed Description

Hepatitis C virus (HCV) infection is a global health problem and it is estimated that about 71 million people are HCV carriers worldwide. Based one the excellent efficacy and safety, interferon (IFN)-free direct-acting antiviral agents (DAAs) have become the standard of care (SOC) for the care of HCV. Currently, about 10 different DAA regimens have been approved by FDA and EMA for the treatment of HCV, the sustained virologic response (SVR) rates are generally more than 95% by these treatment.

Despite the efficacy and safety are excellent in patients receiving DAAs for HCV, about 1%-5% of these patients fail to successfully clear virus by DAA treatment. Retreating patients who fail to respond to DAAs with more potent DAAs would be of paramount importance for treating physicians and patients. Even since 2017, an estimated of 110,000 to 120,000 viremic patients in Taiwan have received governmental reimbursement with DAA treatment. Based on a recent report from National Hepatitis C Program (NHCP) office, about 2% of subjects in Taiwan have virologic failures to DAA treatment, which implies that about 2,200 to 2,400 HCV-infected patients remain viremic with the currently approved first-line DAA therapies. Furthermore, the majority of them have been treated with HCV non-structural 5A (NS5A)-based DAA regimens. Sofosbuvir/velpatasvir/voxilaprevir, a pangenotypic DAA regimen, serves as a rescue therapy for HCV patients who do not respond to first-line DAA treatment. The phase 3 POLARIS-1 trial which retreated HCV patients who failed to respond to NS5A-containing DAAs with SOF/VEL/VOX for 12 weeks revealed that the SVR12 rate was 96%. Among patients without cirrhosis and with compensated cirrhosis, the SVR12 rates were 99% and 93%, respectively. In addition, the phase 3 POLARIS-4 trial which retreated HCV genotype 1a and 3 patients who failed to respond to non-NS5A-containing DAAs with SOF/VEL/VOC for 12 weeks in HCV revealed that the SVR12 rates were 98% and 94%, respectively. Because all patients enrolled in the POLARIS-1 and POLARIS-4 trials who failed to prior genotype-specific DAA regimens, data regarding the effectiveness and safety of SOF/VEL/VOX for patients who failed to prior pangenotypic DAA regimens remain elusive. Two small-scale real-world studies assessing the performance of SOF/VEL/VOX for 12 weeks in patients who failed to pangenotypic SOF/VEL or glecaprevir/pibrentasvir (GLE/PIB) revealed that SVR12 rates were 100% and 94%. Nonetheless, two real-world studies in Western countries showed that the SVR12 rates of SOF/VEL/VOX for 12 weeks ranged from 95%-96% for HCV patients who failed to prior DAA therapies.

Based on the approval of governmental reimbursement of SOF/VEL/VOX retreatment for HCV genotype 1-6 patients who fail to prior NS5A-containing DAA regimens and HCV genotype 1a and 3 patients who fail to prior non-NS5A-containing DAA regimen on September 1, 2021 in Taiwan, the investigators aim to conduct a multicenter observational study to assess the real-world effectiveness and safety of SOF/VEL/VOX for 12 weeks in these patients to provide a powerful evidence to optimize the clinical practice in Taiwan.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Chen-Hua Liu, MD; Phone Number: 63572 +886-223123456; Email: jacque_liu@mail2000.com.tw

Study Locations

• Taiwan
  • Beigang, Taiwan
    • Recruiting
    • China Medical University Beigang Hospital
    • Contact: Ke-Jhang Huang, MD
  • Changhua, Taiwan
    • Recruiting
    • Changhua Christian Hospital
    • Contact: Wei-Wen Su, MD
    • Sub-Investigator: Pei-Yuan Su, MD
  • Chiayi City, Taiwan
    • Recruiting
    • Ditmanson Medical Foundation Chiayi Christian Hospital
    • Contact: Chi-Yi Chen, MD
    • Sub-Investigator: Po-Yueh Chen, MD
  • Chiayi City, Taiwan
    • Recruiting
    • St. Martin De Porres Hospital
    • Contact: Ching-Chu Lo, MD
    • Sub-Investigator: Jow-Jyh Hwang, MD
  • Chiayi City, Taiwan
    • Recruiting
    • Yang Ming Hospital
    • Contact: Chia-Sheng Huang, MD
  • Dalin, Taiwan
    • Recruiting
    • Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
    • Contact: Kuo-Chih Tseng, MD, PhD
    • Sub-Investigator: Chi-Wei Tseng, MD
  • Douliu, Taiwan
    • Recruiting
    • National Taiwan University Hospital, Yun-Lin branch
    • Contact: Yu-Jen Fang, MD
  • Liuying, Taiwan
    • Recruiting
    • Chi-Mei Medical Center, Liouying
    • Contact: Jyh-Jou Chen, MD
    • Sub-Investigator: Pei-Lun Lee, MD
  • New Taipei City, Taiwan
    • Recruiting
    • Fu Jen Catholic University Hospital
    • Contact: Chi-Yang Chang, MD
    • Sub-Investigator: Fu-Jen Lee, MD
  • Taichung, Taiwan
    • Recruiting
    • China Medical University Hospital
    • Sub-Investigator: Hsueh-Chou Lai, MD
  • Taichung, Taiwan
    • Recruiting
    • Taichung Veterans General Hospital
    • Sub-Investigator: Chung-Hsin Chang, MD
    • Sub-Investigator: Yi-Jie Huang, MD
  • Taichung, Taiwan
    • Recruiting
    • Chung Shan Medical University Hospital
    • Contact: Ming-Chang Tsai, MD
  • Taipei, Taiwan
    • Recruiting
    • Taipei Medical University Hospital
    • Contact: Wei-Yu Kao, MD
    • Sub-Investigator: Chun-Chao Chang, MD, PhD
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Chen-Hua Liu, MD, PhD
    • Sub-Investigator: Jia-Horng Kao, MD, PhD
  • Taipei, Taiwan
    • Recruiting
    • Tri-Service General Hospital
    • Contact: Yu-Lueng Shih, MD, PhD
    • Sub-Investigator: Tsai-Yuan Hsieh, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Chronic hepatitis C virus-infected patients who are aged 20 years or more and who are not responded to a prior course of NA5A-containing DAA regimen (all viral genotypes) or to a prior course of non-NS5A-containing DAA regimen (viral genotype 1a or 3). Patients should have compensated liver diseases, and should not take co-medications which are contraindicated for use in the presence of SOF/VEL/VOX.

Description

Inclusion Criteria:

• Chronic hepatitis C virus (HCV) infection, defined as the presence of HCV RNA for ≥ 6 months
• Age ≥ 20 years
• Patients with any HCV genotype (genotype 1-6 or indeterminate genotype) who failed to NS5A-containing DAA regimen or patients with HCV genotype 1a or 3 who failed to non-NS5A-containing DAA regimen

Exclusion Criteria:

• Decompensated cirrhosis
• Patients who receive concomitant medications which are contraindicated for SOF/VEL/VOX, and who decline to stop or switch contraindicated concomitant medications
• Patients who receive therapeutic vaccination or other investigational agents for HCV

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained virologic response (SVR)	Number and percentage of participants who have undetectable serum level of HCV RNA at off-treatment week 12	A total of 24 weeks after the initiation of treatment (drug treatment for 12 weeks and off-treatment follow-up for additional 12 weeks)

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Study Director: Chen-Hua Liu, MD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2021
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): February 28, 2023

Study Registration Dates

• First Submitted: October 3, 2021
• First Submitted That Met QC Criteria: October 11, 2021
• First Posted (Actual): October 25, 2021

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 25, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Hepatitis C virus; Sofosbuvir; Velpatasvir; Voxilaprevir
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Infections; Communicable Diseases; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Velpatasvir
• Other Study ID Numbers: 202109016RIND

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No