Phase 3 Study of Yimitasvir Phosphate Capsules

Study Overview
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Brief Summary
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The safety, tolerability and antiviral activity of DAG181/SOF in treatment-naive and treatment-experienced patients with chronic hepatitis C virus (HCV) genotype 1 infection.

Detailed Description
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A phase III, multicenter, single-arm, open-label study to assess the safety, tolerability and antiviral activity of DAG181/SOF combination for 12 weeks in adult subjects with chronic genotype 1 HCV infection. Approximately 360 HCV genotype 1 subjects without cirrhosis will be enrolled, treatment-experienced subjects are ≤20%. All subjects will receive DAG181 100 mg/ SOF 400 mg once daily for 12 weeks，with subsequent observation for 24 weeks after cessation of treatment.

Official Title
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A Multicenter, Single-arm, Open-label Study to Investigate the Efficacy and Safety of Yimitasvir Phosphate (DAG181)/Sofosbuvir(SOF) Combination for 12 Weeks in Subjects With Chronic Genotype 1 HCV Infection

Conditions
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Chronic HCV Infection

Intervention / Treatment
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* Drug: SOF
* Drug: DAG181


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent; Male or female, age≥18 years; A female subject is eligible to enter the study if it is confirmed that she is: Of non-childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal-women > 50 years of age with cessation (for≥12 months) of previously occurring menses), or Of childbearing potential (Women≤50 years of age with amenorrhea will be considered to be of childbearing potential). These women must have a negative serum pregnancy test at screening and negative urine pregnancy test at baseline before first dose of study drugs, and must use specific contraceptive methods from screening until 90 days after last dose of study drugs, such as complete abstinence from intercourse, vaginal ring, cervical cap or contraceptive diaphragm, IUD, etc. All male subjects must agree to consistently and correctly use specific contraceptive methods with their female partner from screening until 90 days after last dose of study drugs(except for surgical sterilization), such as complete abstinence from intercourse, condom, and their female partner use contraceptives , vaginal ring , cervical cap or contraceptive diaphragm, IUD, etc; Male subjects must agree to refrain from sperm donation from the date of screening until 90 days after the last dose of study drugs; Confirmation of chronic HCV infection documented by either: A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or A liver biopsy performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection. Serological detection of anti-HCV antibodies was positive at screening; HCV RNA≥1×104 IU/mL at Screening; HCV genotype 1a, 1b, or mixed 1a/1b at screening as determined by the Central Laboratory; Classification as treatment naive or treatment experienced; Absence of cirrhosis. Exclusion Criteria: Investigator assessed subjects have other clinically significant abnormalities (other than HCV), such as uncontrollable heart disease, respiratory, gastrointestinal, blood, nervous or other medical disorders, which may interfere with treatment, assessment, or compliance with the protocol; Laboratory results outside of acceptable ranges at Screening; HBsAg serology test results were positive at Screening; HIV antibody test results were positive at Screening; Prior exposure to approved or experimental HCV-specific direct-acting antiviral agent; Pregnant female or male with pregnant female partner.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SOF 400 mg+DAG181 100 mg<br>Patients with genotype 1 HCV infection without cirrhosis will receive SOF 400 mg+DAG181 100 mg for 12 weeks. | Drug: SOF<br>* 400 mg tablet administered orally once daily<br>* Other names: Sovaldi®;Drug: DAG181<br>* 100 mg capsule administered orally once daily<br>* Other names: Yimitasvir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with sustained virologic response 12 weeks after discontinuation of therapy(SVR12) | SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after discontinuation of therapy | Posttreatment Week 12 | 
| Safety and tolerability were evaluated based on adverse events | Collecting all adverse events during the whole study | Up to posttreatment week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects with sustained virologic response 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24) | SVR4 and SVR24 were defined as HCV RNA < the lower limit of quantitation (LLOQ) at 4 and 24 weeks after discontinuation of therapy, respectively. | Posttreatment Weeks 4 and 24 | 
| HCV RNA change from baseline | the quantification of HCV RNA during and after treatment compared with baseline | Up to posttreatment week 24 | 
| Percentage of subjects with virologic failure | On-treatment virologic failure: confirmed HCV RNA ≥ the lower limit of quantitation (LLOQ) after having previously had HCV RNA <the lower limit of quantitation (LLOQ) while on treatment; confirmed ≥ 1 log10 IU/mL increase in HCV RNA from nadir while on treatment; HCV RNA persistently ≥the lower limit of quantitation (LLOQ) through 8 weeks of treatment. Virologic relapse: Confirmed HCV RNA ≥the lower limit of quantitation (LLOQ) during the posttreatment period having achieved HCV RNA <the lower limit of quantitation (LLOQ) at last on-treatment visit. | Up to posttreatment week 24 | 
| Percentage of subjects with viral resistance to DAG181 and/or SOF | Monitoring HCV virus resistance at baseline, during and after treatment | Up to posttreatment week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Genotype 1 HCV Infection