Clinical trial NCT03487107: Phase 3 Study of Yimitasvir Phosphate Capsules
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic HCV Infection
Keywords: Chronic Genotype 1 HCV Infection
Lead sponsor: Sunshine Lake Pharma Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-04-03
Enrollment: 362
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of subjects with sustained virologic response 12 weeks after discontinuation of therapy(SVR12)
timeFrame: Posttreatment Week 12
measure: Safety and tolerability were evaluated based on adverse events
timeFrame: Up to posttreatment week 24
Secondary outcomes:
measure: Percentage of subjects with sustained virologic response 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)
timeFrame: Posttreatment Weeks 4 and 24
measure: HCV RNA change from baseline
timeFrame: Up to posttreatment week 24
measure: Percentage of subjects with virologic failure
timeFrame: Up to posttreatment week 24
measure: Percentage of subjects with viral resistance to DAG181 and/or SOF
timeFrame: Up to posttreatment week 24
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Ditan Hospital Affiliated to Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Peking University First Hospital
state: Beijing
city: Beijing
country: China
facility: Peking University People's Hospital
state: Beijing
city: Beijing
country: China
facility: Beijing Friendship Hospital，Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Beijing YouAn Hospital,Capital Medical University
state: Beijing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary Hospital of Fujian Medical University
state: Fujian
city: Lanzhou
country: China
facility: The First Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Guangzhou Eighth People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital of Southern Medical University
state: Guangdong
city: Haikou
country: China
facility: Hainan General Hospital
state: Hainan
city: Shijiazhuang
country: China
facility: The Third Hospital of Hebei Medical University
state: Hebei
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: People's Hospital of Zhengzhou
state: Henan
city: Wuhan
country: China
facility: The Central Hospital of Wuhan
state: Hubei
city: Wuhan
country: China
facility: Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology
state: Hubei
city: Wuhan
country: China
facility: Tongji Hospital Affiliated to Tongji Medical College of Huazhong University Science & Technology
state: Hubei
city: Wuhan
country: China
facility: Renmin Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: Hunan Provincial People's Hospital
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital, Central South University
state: Hunan
city: Nanjing
country: China
facility: The People's Liberation Army No.81 Hospital
state: Jiangsu
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
state: Jiangsu
city: Wuxi
country: China
facility: The Fifth People's Hospital of Wuxi
state: Jiangsu
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical Hospital
state: Jiangsu
city: Zhenjiang
country: China
facility: The Third People's Hospital of Zhenjiang
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of NanChang University
state: Jiangxi
city: Chang Chun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
state: Liaoning
city: Shanghai
country: China
facility: Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
state: Shanghai
city: Xi'an
country: China
facility: Tangdu Hospital
state: Shanxi
city: Xi'an
country: China
facility: The First Affiliated Hospital of Xi'an Jiaotong University
state: Shanxi
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Chengdu
country: China
facility: Sichuan Provincial People's Hospital
state: Sichuan
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
Study officials:
affiliation: Peking University People's Hospital
name: Lai Wei, Doctor
role: STUDY_CHAIR
References: