Efficacy and Safety of Ravidasvir in Combination With Danoprevir/r and Ribavirin(RBV) in Treatment-naive, Non-cirrhotic, Chronic Hepatitis C Virus Genotype1 Infected Subjects.

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy and safety of Ravidasvir in combination with Danoprevir/r and ribavirin(RBV) by sustain virologic response 12 (SVR12), in treatment-naive, non-cirrhotic, chronic hepatitis C genotype 1 infected patients.

Official Title
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A Phase2/3, Multi-center, Randomized, Double-blind, Placebo-parallel Controlled Study to Investigate the Efficacy and Safety of Ravidasvir in Combination With Danoprevir/r and Ribavirin(RBV) in Treatment-naive, Non-cirrhotic, Chronic Hepatitis C Genotype 1 Infected Subjects.

Conditions
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HCV

Intervention / Treatment
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* Drug: Ravidasvir
* Drug: Danoprevir
* Drug: Ritonavir
* Drug: Ribavirin 100 MG
* Drug: Ravidasvir Placebo
* Drug: Danoprevir Placebo
* Drug: Ritonavir Placebo
* Drug: Ribavirin Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infection with Chronic hepatitis C genotype 1confirmed at screening; Anti-HCV positive； HCV RNA ≥1 × 10000IU / mL; Not treated with interferon and / or any other direct-acting antiviral (DAA) drug; Non-cirrhotic; Voluntarily sign informed consent. Exclusion Criteria: HCV genotypes 2 to 7 or undetectable HCV genotype or mixed HCV genotype; Fibroscan detection result > 12.9kPa or Histopathological examination result of patients is with cirrhosis; Past or existing evidence of the presence of non-HCV-induced chronic liver disease; Previous history of hepatocellular carcinoma, or suspected hepatocellular carcinoma found prior to screening, or suspected abdominal hepatoblastoma at screening or AFP>100ng/mL; Anti-HAV (IgM) 、HBsAg 、anti-HEV (IgM) or anti-HIV is positive; BMI<18 or≥30 kg/m2; ANC<1.5×109/L、PLT<100×109/L、HB<110g/L（female）or<120g/L（male）；INR>1.5；ALT or AST≥5*ULN；TBIL≥2*ULN（DBIL≥ 35%TBIL）；Cr≥1.5*ULN; Others as specified in detailed protocol.

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>Ravidasvir + Danoprevir + Ritonavir + Ribavirin | Drug: Ravidasvir<br>* Ravidasvir 200mg tablet administered orally once daily<br>* Other names: ASC16;Drug: Danoprevir<br>* Danoprevir 100mg tablet administered orally twice daily<br>* Other names: ASC08;Drug: Ritonavir<br>* Ritonavir 100mg tablet administered orally twice daily<br>Drug: Ribavirin 100 MG<br>* Ribavirin tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations(<75kg = 1000mg and ≥75kg = 1200mg)<br>|
| Placebo Comparator: Placebo Group<br>Ravidasvir placebo + Danoprevir placebo + Ritonavir placebo + Ribavirin placebo | Drug: Ravidasvir Placebo<br>* Ravidasvir Placebo tablet administered orally once daily<br>Drug: Danoprevir Placebo<br>* Danoprevir Placebo tablet administered orally twice daily<br>Drug: Ritonavir Placebo<br>* Ritonavir Placebo tablet administered orally twice daily<br>Drug: Ribavirin Placebo<br>* Ribavirin Placebo tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations(<75kg = 5 tablets and ≥75kg = 6 tablets)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants achieving sustained Virologic response 12 weeks after EOT | SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks after cessation of therapy | Post treatment Week 12 | 
| Adverse events leading to permanent discontinuation of study drug |  | baseline to week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants achieving sustained Virologic response 4 weeks after EOT | SVR4 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 4 weeks after cessation of therapy | Post treatment Week 4 | 
| Percentage of Participants achieving sustained Virologic response 24 weeks after EOT | SVR24 was defined as HCV RNA < the lower limit of quantitation (LLOQ) 24 weeks after cessation of therapy | Post treatment Week 24 | 
| Quatitation change of HCV RNA compared to baseline after treatment |  | Baseline to week 1 | 
| Percentage of participants with viral breakthrough | Viral breakthrough was defined as HCV RNA ≥LLOQ after having previously had HCV RNA< LLOQ while receiving treatment, confirmed with 2 consecutive values | Baseline to week 12 | 
| Percentage of participants with viral relapse | Viral relapse was defined as HCV RNA ≥LLOQ during the post treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values. | End of treatment to post-treatment week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV, Ravidasvir, SVR12