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

• Sponsor: Ascletis Pharmaceuticals Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03020095
• Collaborator: (none)
• Enrollment: 38
• Arm: 1
• Duration (Months): 18.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Ravidasvir; Drug: Danoprevir; Drug: Ritonavir; Drug: Ribavirin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 38 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Study Start Date: Aug 1, 2015
• Actual Primary Completion Date: Aug 1, 2016
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

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: Ravidasvir; Ravidasvir 200mg tablet administered orally once daily; Other Names: Asclevir ; Drug: Danoprevir; Danoprevir 100mg tablet administered orally twice daily; Other Names: Ganovo ; Drug: Ritonavir; Ritonavir 100mg tablet administered orally twice daily; Drug: Ribavirin; Ribavirin(RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)administered orally; Other Names: Ribasphere®

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment [12 weeks]

   SVR12, defined as undetectable HCV RNA 12 weeks after the last day of study drug administration.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Ascletis Pharmaceuticals Co., Ltd.

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ascletis Pharmaceuticals Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03020095
• Other Study ID Numbers: ASC162001
• First Posted: Jan 13, 2017
• Last Update Posted: Oct 22, 2020
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ascletis Pharmaceuticals Co., Ltd.: Ravidasvir; HCV GT1; SVR12; Danoprevir/r
• Additional relevant MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin

Study Results

Participant Flow

Arm/Group Title	Ravidasvir,Danoprevir/r,RBV
Arm/Group Description	Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks. Ravidasvir: Ravidasvir 200mg tablet administered orally once daily Danoprevir: Danoprevir 100mg tablet administered orally twice daily Ritonavir: Ritonavir 100mg tablet administered orally twice daily Ribavirin: Ribavirin(RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)administered orally
Period Title: Overall Study
STARTED	38
COMPLETED	37
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ravidasvir,Danoprevir/r,RBV
Arm/Group Description	Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks. Ravidasvir: Ravidasvir 200mg tablet administered orally once daily Danoprevir: Danoprevir 100mg tablet administered orally twice daily Ritonavir: Ritonavir 100mg tablet administered orally twice daily Ribavirin: Ribavirin(RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)administered orally
Overall Participants	38
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56.6 (12.76)
Sex: Female, Male (Count of Participants)
Female	26 68.4%
Male	12 31.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	38 100%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	0 0%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
Taiwan	38 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Ravidasvir,Danoprevir/r,RBV
Arm/Group Description	Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks. Ravidasvir: Ravidasvir 200mg tablet administered orally once daily Danoprevir: Danoprevir 100mg tablet administered orally twice daily Ritonavir: Ritonavir 100mg tablet administered orally twice daily Ribavirin: Ribavirin(RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)administered orally
Measure Participants	38
Count of Participants [Participants]	38 100%

Adverse Events

Arm/Group Title	Ravidasvir,Danoprevir/r,RBV
Arm/Group Description	Participants will receive Ravidasvir 200mg plus Ritonavir boosted Danoprevir 200/200mg,and Ribavirin 1000/1200mg daily for 12 weeks. Ravidasvir: Ravidasvir 200mg tablet administered orally once daily Danoprevir: Danoprevir 100mg tablet administered orally twice daily Ritonavir: Ritonavir 100mg tablet administered orally twice daily Ribavirin: Ribavirin(RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)administered orally
All Cause Mortality
	Ravidasvir,Danoprevir/r,RBV
	Affected / at Risk (%)	# Events
Total	0/38 (0%)
Serious Adverse Events
	Ravidasvir,Danoprevir/r,RBV
	Affected / at Risk (%)	# Events
Total	0/38 (0%)
Other (Not Including Serious) Adverse Events
	Ravidasvir,Danoprevir/r,RBV
	Affected / at Risk (%)	# Events
Total	14/38 (36.8%)
Blood and lymphatic system disorders
anemia	10/38 (26.3%)	10
Gastrointestinal disorders
Diarrhea	6/38 (15.8%)	6

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Ascletis, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The study has been completed at all study sites for at least 3 years.