Efficacy and Safety of Ravidasvir + Danoprevir/r 12-week Oral Therapy in Treatment-Naive Non Cirrhotic G1 CHC Taiwan

Phase 2 Study To Investigate the Efficacy, Safety And Pharmacokinetics Of Ravidasvir In Combination With Ritonavir-boosted Danoprevir And Ribavirin In Treatment-naive Non-cirrhotic Taiwanese Patients Who Have Chronic Hepatitis C Genotype 1

The purpose of this study is to evaluate the efficacy, safety and tolerability of Ravidasvir (ASC16) in combination with Ritonavir-boosted Danoprevir(ASC08) and Ribavirin in treatment-naive no-cirrhotic Taiwanese patients who have chronic hepatitis C genotype1.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: Ritonavir; Drug: Ravidasvir; Drug: Danoprevir; Drug: Ribavirin

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Willing and able to provide written informed consent
• Chronic HCV infection (≥6 months) , HCV RNA ≥ 1 × 104 IU/mL
• Never received prior-treatment for HCV with interferon, RBV, or other direct-acting or host-targeting antivirals for HCV
• Chronic liver disease consistent with CHC infection without cirrhosis as determined by biopsy obtained within the past calendar 36 months using one of the liver biopsy methods in the protocol (non-cirrhosis is defined as: Metavir score ˂ 4), or as determined by Fibroscan defined as: ˂ 14.6 kPa. Patients who have not obtained a liver biopsy or Fibroscan in the last 3 years will have a study related Fibroscan performed in order to confirm the diagnosis. Liver biopsy will be performed by investigator's judgement
• All male patients with female partners of childbearing potential must use two reliable forms of effective contraception (combined) during treatment and for 6 months following the last dose of ribavirin
• Others as specified in detailed protocol.

Exclusion Criteria:

• Pregnant or lactating women.
• History or presence of decompensated liver disease (history of ascites, hepatic encephalopathy, HCC, or bleeding esophageal varices)
• Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, α-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson's disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy
• Positive hepatitis B surface antigen or HIV antibody at screening
• History or presence of liver cirrhosis
• History of severe psychiatric disease, including psychosis and/or depression, who is not able to participate or able to give written informed consent and to comply with the study restrictions
• History of active malignancy within the last 5 years, with the exception of localized or in situ carcinoma (e.g., basal or squamous cell carcinoma of the skin)
• History of severe cardiac disease (e.g., New York Heart Association Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmia's requiring ongoing treatment, unstable angina or other unstable, uncontrolled or significant cardiovascular disease within 6 months). Patients with stable coronary artery disease (e.g., 6 months after by-pass surgery, angioplasty with or without stent placement, etc.) as confirmed by a cardiologist will be permitted. In addition, patients with documented or presumed unstable coronary artery disease, cardiovascular disease, or cerebrovascular disease should not be enrolled.
• Any patient with an increased risk for anemia (e.g., thalassemia, sickle cell anemia, or spherocytosis) or for whom anemia would be medically problematic
• History of pre-existing renal disease, patients with a history of nephrolithiasis will be allowed
• Others as specified in detailed protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ravidasvir,Danoprevir/r,RBV; Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks.	Drug: Ritonavir; Ritonavir 100mg tablet administered orally twice daily; Drug: Ravidasvir; Ravidasvir 200mg tablet administered orally once daily; Other Names: Asclevir; Drug: Danoprevir; Danoprevir 100mg tablet administered orally twice daily; Other Names: Ganovo; Drug: Ribavirin; Ribavirin(RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)administered orally; Other Names: Ribasphere®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment	SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration.	12 weeks

Collaborators and Investigators

• Sponsor: Ascletis Pharmaceuticals Co., Ltd.
• Investigators: Study Director: Huoling Tang, PhD, Ascletis Pharmaceuticals Co., Ltd.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): August 1, 2016
• Study Completion (Actual): February 1, 2017

Study Registration Dates

• First Submitted: January 5, 2017
• First Submitted That Met QC Criteria: January 11, 2017
• First Posted (Estimate): January 13, 2017

Study Record Updates

• Last Update Posted (Actual): October 22, 2020
• Last Update Submitted That Met QC Criteria: October 20, 2020
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: SVR12; HCV GT1; Ravidasvir; Danoprevir/r
• 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; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ribavirin; Ritonavir
• Other Study ID Numbers: ASC162001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No