Efficacy and Safety of Danoprevir/r + PR 12week Triple Therapy in Treatment Naive Non-Cirrhotic G1 CHC China III

• Sponsor: Ascletis Pharmaceuticals Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03020082
• Collaborator: (none)
• Enrollment: 141
• Arm: 1
• Duration (Months): 11

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy and safety of Ritonavir-boosted ASC08 (Danoprevir) in Combination with Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis Genotype 1.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Danoprevir; Drug: Ritonavir; Drug: peginterferon alfa-2a; Drug: RBV	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 141 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-centered, Open Label, Phase III Study on Efficacy, Safety of Ritonavir-boosted ASC08 (Danoprevir) in Combination With Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis Genotype 1
• Study Start Date: Jun 1, 2016
• Actual Primary Completion Date: May 1, 2017
• Actual Study Completion Date: May 1, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Danoprevir, Ritonavir, Peg-IFN,RBV Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks.

Drug: Danoprevir; Danoprevir (DNV)administered orally 100mg BID for 12 weeks; Other Names: ASC08 ; Drug: Ritonavir; Ritonavir administered orally 100mg BID for 12 weeks; Drug: peginterferon alfa-2a; PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks; Other Names: Peg-IFN ; Drug: RBV; RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.; Other Names: Ribasphere®

Outcome Measures

Primary Outcome Measures

1. Proportion of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12) [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 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)

• Serum HCV RNA of ≥ 1 × 104 IU/mL are documented

• Hepatitis C virus GT1

• Never received prior-treatment for HCV with interferon, RBV, or other direct-acting or host-targeting antivirals for HCV

• Non-cirrhosis patients: Non-cirrhosis is defined (1)Fibroscan defined as: ˂ 14.6 kPa during screening period, or liver biopsy determined 1 year before recruiting (Metavir score ˂ 3);(2) during screening period 9.6<Fibroscan indicator ≤12.9, liver biopsy need to confirm non-cirrhosis.

• Others as specified in the detailed protocol

Exclusion Criteria:

• Patients with Fibroscan detection value > 12.9 kPa, or histologic examination for liver cirrhosis patients

• Presence or history of non-hepatitis C chronic liver disease (e.g. HH, AIH, Wilson's disease, α1 antitrypsin deficiency, drug- or toxin-induced liver disease)

• History of liver cell cancer, or suspected hepatocellular carcinoma (HCC) patients before or during screening , or imaging studies found suspicious nodules, or AFP > 50 ng/mL

• Positive hepatitis A antibody，positive hepatitis B surface antigen，HIV antibody

• Presence or history of nervous system diseases and/or mental illness, inability to control oneself or express oneself.

• Patients with obvious cardiovascular dysfunction

• Pregnant or nursing female, nor unwilling to take reliable contraception

• Others as specified in the 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)

• Statistical Analysis Plan - Mar 21, 2017
• Study Protocol - Jan 16, 2017

More Information

Publications

None provided.

• Responsible Party: Ascletis Pharmaceuticals Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03020082
• Other Study ID Numbers: ASC08201503
• First Posted: Jan 13, 2017
• Last Update Posted: Mar 23, 2021
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Ascletis Pharmaceuticals Co., Ltd.: Danoprevir; non-cirrhotic; Chinese HCV G1; SVR12
• Additional relevant MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Peginterferon alfa-2a; Ribavirin

Study Results

Participant Flow

Arm/Group Title	Danoprevir, Ritonavir, Peg-IFN,RBV
Arm/Group Description	Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks. Danoprevir: Danoprevir (DNV)administered orally 100mg BID for 12 weeks; Ritonavir: Ritonavir administered orally 100mg BID for 12 weeks; peginterferon alfa-2a: PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks; RBV: RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.
Period Title: Overall Study
STARTED	141
COMPLETED	138
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Danoprevir, Ritonavir, Peg-IFN,RBV
Arm/Group Description	Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks. Danoprevir: Danoprevir (DNV)administered orally 100mg BID for 12 weeks; Ritonavir: Ritonavir administered orally 100mg BID for 12 weeks; peginterferon alfa-2a: PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks; RBV: RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.
Overall Participants	141
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	42 (12.1)
Sex: Female, Male (Count of Participants)
Female	70 49.6%
Male	71 50.4%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	141 100%
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%

Outcome Measures

1. Primary Outcome

Title	Proportion of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Danoprevir, Ritonavir, Peg-IFN,RBV
Arm/Group Description	Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks. Danoprevir: Danoprevir (DNV)administered orally 100mg BID for 12 weeks; Ritonavir: Ritonavir administered orally 100mg BID for 12 weeks; peginterferon alfa-2a: PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks; RBV: RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.
Measure Participants	141
Count of Participants [Participants]	136 96.5%

Adverse Events

Time Frame	24 weeks
Arm/Group Title	Danoprevir, Ritonavir, Peg-IFN,RBV
Arm/Group Description	Participants will receive Ritonavir- boosted Danoprevir 100mg/100mg BID in combination with subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg for 12 weeks. Danoprevir: Danoprevir (DNV)administered orally 100mg BID for 12 weeks; Ritonavir: Ritonavir administered orally 100mg BID for 12 weeks; peginterferon alfa-2a: PEG-IFN abdominal or thigh subcutaneous injection, 180μg, once a week for 12 weeks; RBV: RBV administered orally 500mg (5 tablets)( body weight <75Kg) BID, 600mg (6 tablets) BID body weight ≥75Kg, for 12 weeks.
All Cause Mortality
	Danoprevir, Ritonavir, Peg-IFN,RBV
	Affected / at Risk (%)	# Events
Total	0/141 (0%)
Serious Adverse Events
	Danoprevir, Ritonavir, Peg-IFN,RBV
	Affected / at Risk (%)	# Events
Total	5/141 (3.5%)
Blood and lymphatic system disorders
neutropenia	1/141 (0.7%)
Cardiac disorders
Ventricular tachyarrhythmia	1/141 (0.7%)
Eye disorders
Acquired digital fibrokeratoma	1/141 (0.7%)
Infections and infestations
Tuberculosis	1/141 (0.7%)
Metabolism and nutrition disorders
Transient ischemic attack	1/141 (0.7%)
Other (Not Including Serious) Adverse Events
	Danoprevir, Ritonavir, Peg-IFN,RBV
	Affected / at Risk (%)	# Events
Total	76/141 (53.9%)
Blood and lymphatic system disorders
Anemia	76/141 (53.9%)
Infections and infestations
Fever	53/141 (37.6%)

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.