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.

Sponsor

Ascletis Pharmaceuticals Co., Ltd. (Industry)

Overall Status

Completed

CT.gov ID

NCT03362814

Collaborator

(none)

425

Enrollment

Location

Arms

21.7

Actual Duration (Months)

19.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
HCV	Drug: Ravidasvir Drug: Danoprevir Drug: Ritonavir Drug: Ribavirin 100 MG Drug: Ravidasvir Placebo Drug: Danoprevir Placebo Drug: Ritonavir Placebo Drug: Ribavirin Placebo	Phase 2/Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

425 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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.

Actual Study Start Date :

Jul 1, 2017

Actual Primary Completion Date :

Dec 12, 2018

Actual Study Completion Date :

Apr 24, 2019

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Experimental Group

Ravidasvir + Danoprevir + Ritonavir + Ribavirin

Drug: Ravidasvir

Ravidasvir 200mg tablet administered orally once daily

Other Names:

ASC16

Drug: Danoprevir

Danoprevir 100mg tablet administered orally twice daily

Other Names:

ASC08

Drug: Ritonavir

Ritonavir 100mg tablet administered orally twice daily

Drug: Ribavirin 100 MG

Ribavirin tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations(<75kg = 1000mg and ≥75kg = 1200mg)

Placebo Comparator: Placebo Group

Ravidasvir placebo + Danoprevir placebo + Ritonavir placebo + Ribavirin placebo

Drug: Ravidasvir Placebo

Ravidasvir Placebo tablet administered orally once daily

Drug: Danoprevir Placebo

Danoprevir Placebo tablet administered orally twice daily

Drug: Ritonavir Placebo

Ritonavir Placebo tablet administered orally twice daily

Drug: Ribavirin Placebo

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)

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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≥5ULN；TBIL≥2ULN（DBIL≥ 35%TBIL）；Cr≥1.5*ULN;
Others as specified in detailed protocol.