Clinical trial NCT05092074: Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) for Patients With Hepatitis C Virus Infection
Official title: Sofosbuvir/Velpatasvir/Voxilaprevir (SOF/VEL/VOX) for Patients With Hepatitis C Virus Infection: Real-world Effectiveness and Safety in Taiwan
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hepatitis C Virus Infection
Treatment Side Effects
Adherence, Treatment
Effect of Drug
Keywords: Hepatitis C virus
Sofosbuvir
Velpatasvir
Voxilaprevir
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2021-10-25
Enrollment: 100
Sex: ALL
Minimum age (years): 20
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Sustained virologic response (SVR)
timeFrame: A total of 24 weeks after the initiation of treatment (drug treatment for 12 weeks and off-treatment follow-up for additional 12 weeks)
Secondary outcomes:
Other outcomes:
Locations:
city: Beigang
country: Taiwan
facility: China Medical University Beigang Hospital
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital
city: Chiayi City
country: Taiwan
facility: Ditmanson Medical Foundation Chiayi Christian Hospital
city: Chiayi City
country: Taiwan
facility: St. Martin De Porres Hospital
city: Chiayi City
country: Taiwan
facility: Yang Ming Hospital
city: Dalin
country: Taiwan
facility: Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
city: Douliu
country: Taiwan
facility: National Taiwan University Hospital, Yun-Lin Branch
city: Liuying
country: Taiwan
facility: Chi-Mei Medical Center, Liouying
city: New Taipei City
country: Taiwan
facility: Fu Jen Catholic University Hospital
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Medical University Hospital
city: Taipei
country: Taiwan
facility: Tri-Service General Hospital
Study officials:
affiliation: National Taiwan University Hospital
name: Chen-Hua Liu, MD
role: STUDY_DIRECTOR
References: