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.

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.

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.

Study Overview

• Status: Completed
• Conditions: HCV
• Intervention / Treatment: Drug: Ritonavir; Drug: Ravidasvir; Drug: Danoprevir; Drug: Ribavirin 100 MG; Drug: Ravidasvir Placebo; Drug: Danoprevir Placebo; Drug: Ritonavir Placebo; Drug: Ribavirin Placebo

• Study Type: Interventional
• Enrollment (Actual): 425
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Experimental Group; Ravidasvir + Danoprevir + Ritonavir + Ribavirin	Drug: Ritonavir; Ritonavir 100mg tablet administered orally twice daily; 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: 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ascletis Pharmaceuticals Co., Ltd.
• Investigators: Study Director: Yahong Chen, Master, Ascletis Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 1, 2017
• Primary Completion (ACTUAL): December 12, 2018
• Study Completion (ACTUAL): April 24, 2019

Study Registration Dates

• First Submitted: November 28, 2017
• First Submitted That Met QC Criteria: December 4, 2017
• First Posted (ACTUAL): December 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 28, 2020
• Last Update Submitted That Met QC Criteria: July 25, 2020
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: HCV; SVR12; Ravidasvir
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ribavirin; Ritonavir; Lactams
• Other Study ID Numbers: ASC-ASC16-II/III-CTP-1-01

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