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

• Sponsor: Ascletis Pharmaceuticals Co., Ltd. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03020004
• Collaborator: (none)
• Enrollment: 70
• Arm: 1
• Duration (Months): 13

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the Efficacy, Safety and Pharmacokinetics of Ritonavir-boosted Danoprevir (ASC08) 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: Ribavirin (RBV)	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 70 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2,Multicenter,Open-Label Study to Investigate the Efficacy, Safety and Pharmacokinetics of Ritonavir-boosted Danoprevir in Combination With Peg-IFN and RBV in Treatment-Naive Non-Cirrhotic Patients Who Have Chronic Hepatitis GT1
• Study Start Date: Jan 1, 2016
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Danoprevir,Ritonavir, Peg-IFN,RBV Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg) for 12 weeks.	Drug: Danoprevir; Danoprevir (DNV) 100mg tablet administered orally twice daily; Other Names: ASC08 ; Drug: Ritonavir; Ritonavir 100mg tablet administered orally twice daily; Drug: peginterferon alfa-2a; PegIFN subcutaneous injection at 180 mcg weekly; Other Names: PegIFN ; Drug: Ribavirin (RBV); Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg); Other Names: Ribasphere®

Outcome Measures

Primary Outcome Measures

1. Percentage of Subjects With Sustained Virologic Response (SVR12) 12 Weeks Post-treatment [24 weeks]

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

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) ;

• Positive HCV antibody

• Serum HCV RNA of ≥ 1 × 104 IU/mL

• Hepatitis C virus GT1

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

• 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 1 years will have a study related Fibroscan performed in order to confirm the diagnosis

• 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, 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

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

• Positive hepatitis A antibody，positive hepatitis B surface antigen，syphilis antibody or HIV antibody at screening

• 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)

None provided.

More Information

Publications

None provided.

• Responsible Party: Ascletis Pharmaceuticals Co., Ltd.
• ClinicalTrials.gov Identifier: NCT03020004
• Other Study ID Numbers: ASC08201502
• First Posted: Jan 13, 2017
• Last Update Posted: Jul 26, 2018
• 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; SVR12; Chinese HCV G1; non-cirrhotic
• Additional relevant MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic; Ritonavir; Ribavirin; Peginterferon alfa-2a

Study Results

Participant Flow

Arm/Group Title	Danoprevir,Ritonavir, Peg-IFN,RBV
Arm/Group Description	Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg) for 12 weeks. Danoprevir: Danoprevir (DNV) 100mg tablet administered orally twice daily Ritonavir: Ritonavir 100mg tablet administered orally twice daily peginterferon alfa-2a: PegIFN subcutaneous injection at 180 mcg weekly Ribavirin (RBV): Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)
Period Title: Overall Study
STARTED	70
COMPLETED	69
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Danoprevir,Ritonavir, Peg-IFN,RBV
Arm/Group Description	Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg) for 12 weeks. Danoprevir: Danoprevir (DNV) 100mg tablet administered orally twice daily Ritonavir: Ritonavir 100mg tablet administered orally twice daily peginterferon alfa-2a: PegIFN subcutaneous injection at 180 mcg weekly Ribavirin (RBV): Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)
Overall Participants	70
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.2 (12.4)
Sex: Female, Male (Count of Participants)
Female	30 42.9%
Male	40 57.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	70 100%
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	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	24 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Danoprevir,Ritonavir, Peg-IFN,RBV
Arm/Group Description	Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg) for 12 weeks. Danoprevir: Danoprevir (DNV) 100mg tablet administered orally twice daily Ritonavir: Ritonavir 100mg tablet administered orally twice daily peginterferon alfa-2a: PegIFN subcutaneous injection at 180 mcg weekly Ribavirin (RBV): Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)
Measure Participants	70
Count of Participants [Participants]	66 94.3%

Adverse Events

Arm/Group Title	Danoprevir,Ritonavir, Peg-IFN,RBV
Arm/Group Description	Participants will receive a combination of Ritonavir-boosted Danoprevir 100mg/100mg BID, subcutaneous injection of weekly peginterferon alfa-2a at 180 mcg and oral Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg) for 12 weeks. Danoprevir: Danoprevir (DNV) 100mg tablet administered orally twice daily Ritonavir: Ritonavir 100mg tablet administered orally twice daily peginterferon alfa-2a: PegIFN subcutaneous injection at 180 mcg weekly Ribavirin (RBV): Ribavirin (RBV)1000/1200 mg/day (bodyweight<75/≥75 kg)
All Cause Mortality
	Danoprevir,Ritonavir, Peg-IFN,RBV
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Danoprevir,Ritonavir, Peg-IFN,RBV
	Affected / at Risk (%)	# Events
Total	1/70 (1.4%)
Gastrointestinal disorders
acute pancreatitis	1/70 (1.4%)	1
Other (Not Including Serious) Adverse Events
	Danoprevir,Ritonavir, Peg-IFN,RBV
	Affected / at Risk (%)	# Events
Total	70/70 (100%)
Investigations
Neutrophil count decreased	63/70 (90%)	85
White blood cell decreased	58/70 (82.9%)	69

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.