Phase 3 Study of Yimitasvir Phosphate Capsules

A Multicenter, Single-arm, Open-label Study to Investigate the Efficacy and Safety of Yimitasvir Phosphate (DAG181)/Sofosbuvir(SOF) Combination for 12 Weeks in Subjects With Chronic Genotype 1 HCV Infection

The safety, tolerability and antiviral activity of DAG181/SOF in treatment-naive and treatment-experienced patients with chronic hepatitis C virus (HCV) genotype 1 infection.

Study Overview

• Status: Completed
• Conditions: Chronic HCV Infection
• Intervention / Treatment: Drug: SOF; Drug: DAG181

Detailed Description

A phase III, multicenter, single-arm, open-label study to assess the safety, tolerability and antiviral activity of DAG181/SOF combination for 12 weeks in adult subjects with chronic genotype 1 HCV infection.

Approximately 360 HCV genotype 1 subjects without cirrhosis will be enrolled, treatment-experienced subjects are ≤20%. All subjects will receive DAG181 100 mg/ SOF 400 mg once daily for 12 weeks，with subsequent observation for 24 weeks after cessation of treatment.

• Study Type: Interventional
• Enrollment (Actual): 362
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
    • Beijing, Beijing, China, 100050
      • Beijing Friendship Hospital,Capital Medical University
    • Beijing, Beijing, China, 100069
      • Beijing youan hospital，capital medical university
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
    • Beijing, Beijing, China, 100020
      • Beijing Ditan Hospital Affiliated to Capital Medical University
  • Fujian
    • Fuzhou, Fujian, China, 350025
      • Mengchao Hepatobiliary Hospital of Fujian Medical University
    • Fuzhou, Fujian, China, 350005
      • The First Affiliated Hospital of Fujian Medical University
  • Gansu
    • Lanzhou, Gansu, China, 730000
      • The First Hospital of Lanzhou University
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
    • Guangzhou, Guangdong, China, 510060
      • Guangzhou Eighth People's Hospital
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
  • Hebei
    • Shijiazhuang, Hebei, China, 050051
      • The Third Hospital of Hebei Medical University
  • Henan
    • Xinxiang, Henan, China, 453100
      • The First Affiliated Hospital of Xinxiang Medical University
    • Zhengzhou, Henan, China, 450003
      • People's Hospital of Zhengzhou
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
    • Wuhan, Hubei, China, 430010
      • The Central Hospital of Wuhan
    • Wuhan, Hubei, China, 430022
      • Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital Affiliated to Tongji Medical College of Huazhong University Science & Technology
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital, Central South University
    • Changsha, Hunan, China, 410000
      • Hunan Provincial People's Hospital
  • Jiangsu
    • Nanjing, Jiangsu, China, 210003
      • The Second Hospital of Nanjing
    • Nanjing, Jiangsu, China, 210002
      • The People's Liberation Army No.81 Hospital
    • Wuxi, Jiangsu, China, 214073
      • The Fifth People's Hospital of Wuxi
    • Xuzhou, Jiangsu, China, 221002
      • The Affiliated Hospital of Xuzhou Medical Hospital
    • Zhenjiang, Jiangsu, China, 212004
      • The Third People's Hospital of Zhenjiang
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • The First Affiliated Hospital of Nanchang University
  • Jilin
    • Chang Chun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China, 110006
      • The Sixth People's Hospital of Shenyang
  • Shanghai
    • Shanghai, Shanghai, China, 200020
      • Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
    • Shanghai, Shanghai, China, 201500
      • Shanghai Public Health Clinical Center
  • Shanxi
    • Xi'an, Shanxi, China, 710038
      • Tangdu Hospital
    • Xi'an, Shanxi, China, 710061
      • The First Affiliated Hospital Of Xi'an Jiaotong University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital, Sichuan University
    • Chengdu, Sichuan, China, 610072
      • Sichuan Provincial People's Hospital
  • Zhejiang
    • Wenzhou, Zhejiang, China, 325000
      • The First Affiliated Hospital of Wenzhou Medical University

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:

1. Willing and able to provide written informed consent;
2. Male or female, age≥18 years;

3. A female subject is eligible to enter the study if it is confirmed that she is:

   1. Of non-childbearing potential (i.e., women who have had a hysterectomy, have both ovaries removed or medically documented ovarian failure, or are postmenopausal-women > 50 years of age with cessation (for≥12 months) of previously occurring menses), or
   2. Of childbearing potential (Women≤50 years of age with amenorrhea will be considered to be of childbearing potential). These women must have a negative serum pregnancy test at screening and negative urine pregnancy test at baseline before first dose of study drugs, and must use specific contraceptive methods from screening until 90 days after last dose of study drugs, such as complete abstinence from intercourse, vaginal ring, cervical cap or contraceptive diaphragm, IUD, etc.
4. All male subjects must agree to consistently and correctly use specific contraceptive methods with their female partner from screening until 90 days after last dose of study drugs(except for surgical sterilization), such as complete abstinence from intercourse, condom, and their female partner use contraceptives , vaginal ring , cervical cap or contraceptive diaphragm, IUD, etc;
5. Male subjects must agree to refrain from sperm donation from the date of screening until 90 days after the last dose of study drugs;

6. Confirmation of chronic HCV infection documented by either:

   1. A positive anti-HCV antibody test or positive HCV RNA or positive HCV genotyping test at least 6 months prior to the Baseline/Day 1 visit, or
   2. A liver biopsy performed prior to the Baseline/Day 1 visit with evidence of chronic HCV infection.
7. Serological detection of anti-HCV antibodies was positive at screening;
8. HCV RNA≥1×104 IU/mL at Screening;
9. HCV genotype 1a, 1b, or mixed 1a/1b at screening as determined by the Central Laboratory;
10. Classification as treatment naive or treatment experienced;
11. Absence of cirrhosis.

Exclusion Criteria:

1. Investigator assessed subjects have other clinically significant abnormalities (other than HCV), such as uncontrollable heart disease, respiratory, gastrointestinal, blood, nervous or other medical disorders, which may interfere with treatment, assessment, or compliance with the protocol;
2. Laboratory results outside of acceptable ranges at Screening;
3. HBsAg serology test results were positive at Screening;
4. HIV antibody test results were positive at Screening;
5. Prior exposure to approved or experimental HCV-specific direct-acting antiviral agent;
6. Pregnant female or male with pregnant female partner.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SOF 400 mg+DAG181 100 mg; Patients with genotype 1 HCV infection without cirrhosis will receive SOF 400 mg+DAG181 100 mg for 12 weeks.	Drug: SOF; 400 mg tablet administered orally once daily; Other Names: sofosbuvir; Sovaldi®; Drug: DAG181; 100 mg capsule administered orally once daily; Other Names: Yimitasvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects with sustained virologic response 12 weeks after discontinuation of therapy(SVR12)	SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after discontinuation of therapy	Posttreatment Week 12
Safety and tolerability were evaluated based on adverse events	Collecting all adverse events during the whole study	Up to posttreatment week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of subjects with sustained virologic response 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)	SVR4 and SVR24 were defined as HCV RNA < the lower limit of quantitation (LLOQ) at 4 and 24 weeks after discontinuation of therapy, respectively.	Posttreatment Weeks 4 and 24
HCV RNA change from baseline	the quantification of HCV RNA during and after treatment compared with baseline	Up to posttreatment week 24
Percentage of subjects with virologic failure	On-treatment virologic failure:confirmed HCV RNA ≥ the lower limit of quantitation (LLOQ) after having previously had HCV RNA <the lower limit of quantitation (LLOQ) while on treatment;confirmed ≥ 1 log10 IU/mL increase in HCV RNA from nadir while on treatment;HCV RNA persistently ≥the lower limit of quantitation (LLOQ) through 8 weeks of treatment.; Virologic relapse:Confirmed HCV RNA ≥the lower limit of quantitation (LLOQ) during the posttreatment period having achieved HCV RNA <the lower limit of quantitation (LLOQ) at last on-treatment visit.	Up to posttreatment week 24
Percentage of subjects with viral resistance to DAG181 and/or SOF	Monitoring HCV virus resistance at baseline, during and after treatment	Up to posttreatment week 24

Collaborators and Investigators

• Sponsor: Sunshine Lake Pharma Co., Ltd.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 17, 2018
• Primary Completion (ACTUAL): March 28, 2019
• Study Completion (ACTUAL): June 25, 2019

Study Registration Dates

• First Submitted: March 26, 2018
• First Submitted That Met QC Criteria: April 1, 2018
• First Posted (ACTUAL): April 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): March 18, 2020
• Last Update Submitted That Met QC Criteria: March 16, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Chronic Genotype 1 HCV Infection
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis; Infections; Hepatitis C; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Yimitasvir
• Other Study ID Numbers: PCD-DDAG181PA-16-007

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