KW-136 With Sofosbuvir for Chinese Adults With Chronic Hepatitis C

NCT03995485 | Completed Phase 3

• 2 other identifiers: KYGL-2017-001CTR20171654
• Study Type: interventional
• Target: 371
• Locations: 1 country
• Sites: 19

Brief Summary

This study aimed to confirm efficacy and safety of KW-136, an investigational anti-hepatitis C virus (HCV) drug, combined with sofosbuvir for treatment of naive and experienced adults chronically infected with HCV. Three hundred and sixty (360) non-cirrhotic and cirrhotic subjects were medicated with KW-136 60 mg daily and sofosbuvir 400 mg daily. The treatment course lasted 12 successive weeks; thereafter all the study participants entered into a 12-week treatment-free follow-up period and an additional 12-week extension treatment-free follow-up period.

Conditions

Hepatitis C, Chronic

Keywords

Chronic hepatitis C; Hepatitis C virus; Eradication; KW-136; Sofosbuvir; Nonstructural protein 5A; Nonstructural protein 5B; Panogentypic regimen; Confirmatory study

Outcome Measures

Primary Outcomes (1)

• Sustained virologic response at 12 weeks after end of treatment (SVR12)

  Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)

  12 weeks after end of treatment

Secondary Outcomes (6)

• Sustained virologic response at 4 weeks after end of treatment (SVR4)

  4 weeks after end of treatment

• Rapid virologic response at 1 week after initiation of treatment (RVR1)

  1 week after initiation of treatment

• Rapid virologic response at 2 weeks after initiation of treatment (RVR2)

  2 weeks after initiation of treatment

• Rapid virologic response at 4 weeks after initiation of treatment (RVR4)

  4 weeks after initiation of treatment

• Rapid virologic response at 8 weeks after initiation of treatment (RVR8)

  8 weeks after initiation of treatment

Other Outcomes (3)

• Sustained virologic response at 24 weeks after end of treatment (SVR24)

  24 weeks after end of treatment

• Virologic breakthrough

  2, 4, 8 and 12 weeks after initiation of treatment

• Virologic relapse

  4,12 and 24 weeks after end of treatment

Study Arms (1)

KW-136+SOF

EXPERIMENTAL

Treatment-naive and experienced subjects were medicated with KW-136 capsules 60 mg once daily and fixed-dose (400 mg once daily) sofosbuvir tablets for 12 successive weeks.

Drug: KW-136 capsule; Drug: Sofosbuvir

Interventions

KW-136 capsule DRUG

KW-136 60 mg was provided in a single capsule of 60 mg.

Also known as: Coblopasvir

KW-136+SOF

Sofosbuvir DRUG

Sofosbuvir was provided in a single tablet of 400 mg.

KW-136+SOF

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• aged between 18 and 70 years (both inclusive) at the time of informed consenting and of either sex
• with a body mass index (BMI) between 18 and 32 kg/m\^2 (both inclusive)
• chronically infected with HCV, namely, with positive anti-HCV, HCV RNA or genotyping results at least six (6) months before the screening, or with a liver biopsy confirming chronic hepatitis at most twelve (12) months before the screening or within the screening period
• with anti-HCV positivity and at least once testing result with HCV RNA equaling to or above 10\^4 IU/mL within the screening period
• with gentoype 1, 2, 3, 4, 5, 6, mixed, indeterminate or other genotype by the centralized laboratory genotyping
• no more than ten percent (10%) of the enrolled subjects having previously experienced interferon (defined as having received any regulatory agency approved or investigational interferon formulations, including pegylated and regular interferons at least six \[6\] months before the screening)
• having not previously experienced any other approved, investigational or unapproved direct antiviral agents against HCV of any source
• having not previously experienced oral or injective ribavirin within three (3) months before the screening
• no more than ten percent (10%) of the enrolled patients having advanced fibrosis or compensatory cirrhosis (as documented by liver transient elastography \[FibroScan\] within the screening period, or liver biopsy within twelve \[12\] months before the screening or within the screening period, with an evidence priority over FibroScan result and with the most recent biopsy prevailing in case of inconsistency between liver biopsy and FibroScan result), in accordance with the following definitions of liver disease: no advanced fibrosis or cirrhosis, with a liver stiffness modulus (LSM) below 9.6 kPa and/or F0-2 on fibrosis staging; advanced fibrosis, with a LSM equaling to or above 9.6 kPa but below 14.6 kPa and/or F3 on fibrosis staging; and cirrhosis, with a LSM equaling to or above 14.6 kPa and/or F4 on fibrosis staging
• women of childbearing potential (including postmenopausal women at or under 50 years of age) with negative blood pregnancy test results, and subjects of childbearing potential (including male subjects and their female partners) having no childbearing plan and consenting to voluntarily use effective contraceptive measures from the screening until six (6) months after the end of treatment
• lactating women consenting to discontinue nursing from the screening until six (6) months after the end of treatment
• voluntarily participating in this trial and being able to understand and sign the informed consent form

You may not qualify if:

• having previously experienced any investigational or experimental direct antiviral agents against HCV, including protease inhibitor, nonstructural protein (NS) 5A inhibitor or NS5B polymerase inhibitor, before the screening NS5B polymerase or NS5A inhibitors, before the screening
• having previously experienced interferon-based antiviral regimens within six (6) months before the screening
• having previously experienced oral or injective ribavirin within three (3) months before the screening
• having previously experienced any systemic potent immunomodulatory agents, such as steroids or thymosin alfa, excluding nasal, inhalational, topical steroids and/or others, for more than two (2) weeks within six (6) months before the screening, or expected to be exposed to these agents during the study period
• with hepatitis B virus surface antigen (HBsAg) or anti-human immunodeficient virus (HIV) positivity
• with evidence of decompensatory liver function, including but not limited to total serum bilirubin (TBIL) above twice (2) of the upper limit of normal (ULN), serum albumin (ALB) below 35 g/L or prothrombin activity (PTA) below 60% confirmed on repeated testing, previous or present history of ascites, upper gastrointestinal bleeding and/or hepatic encephalopathy, or with a liver function reserve of Child-Pugh class B or C
• with primary liver cancer confirmed or evidenced by serum alfa-fetoprotein (AFP) above 100 ng/ml or liver imaging study showing suspected nodules
• with a previous history of liver disease of other causes, including alcoholic liver disease, nonalcoholic steatohepatitis, drug-induced hepatitis, autoimmune hepatitis, Wilson disease or hemochromatosis
• with serum alanine aminotransferase (ALT) or asparate aminotransferase (AST) above ten (10) times of the ULN confirmed on repeated testing
• with white blood cell (WBC) count below 3×10\^9 per liter, neutrophil count below 1.5×10\^9 per liter (or below 1.25×10\^9 per liter for cirrhotics), platelet count below 50×10\^9 per liter, or hemoglobin below 100 g/L confirmed on repeated testing
• with serum creatinine clearance (CLcr) below 50 ml/min using the Cockcroft-Gault formula confirmed on repeated testing
• with poorly controlled diabetes mellitus (hemoglobin A1c \[HbA1c\] above 8.0% confirmed on repeated testing)
• with psychiatric or neurologic disorders, including previous or family history of psychiatric disorders (especially depression, depressive state, epilepsy or hysteria)
• with serious cardiovascular disorders, including uncontrolled hypertension (systolic blood pressure at or above 160 mmHg and/or diastolic blood pressure at or above 100 mmHg), heart insufficiency of New York Heart Association class III or above, history of myocardial infarction within six (6) months before the screening, history of percutaneous transluminal coronary angioplasty within six (6) months before the screening, unstable angina pectoris, or QTc interval (Fridericia correction formula QTc = QT×RR\^-1/3) at or above 450 msec for males or 470 msec for females, second- or third-grade atrioventricular block or any other uncontrolled arrhythmias confirmed on repeated electrocardiography on screening
• with serious hematologic disorders, such as anemia, hemophilia and others

Sponsors & Collaborators

• Kawin Technology Share-holding Co., Ltd.: lead
• KawinGreen Biotech Co., Ltd.: collaborator

Study Sites (19)

Chinese PLA 302 Hospital

Beijing, Beijing Municipality, 100039, China

Location

Capital Medical University Affiliated Beijing Youyi Hospital

Beijing, Beijing Municipality, 100050, China

Location

Capital Medical University Affiliated Beijing You'an Hospital

Beijing, Beijing Municipality, 100069, China

Location

Capital Medical University Affiliated Beijing Ditan Hospital

Beijing, Beijing Municipality, 100102, China

Location

Chinese PLA Third Military Medical University First Affiliated Hospital

Chongqing, Chongqing Municipality, 400038, China

Location

Chongqing Sanxia Central Hospital

Wanzhou, Chongqing Municipality, 404000, China

Location

Sun Yat-sen University Affiliated Third University

Guangzhou, Guangdong, 510630, China

Location

Guangzhou Municipal Eighth People's Hospital

Guanzhou, Guangdong, 510060, China

Location

Liuzhou People's Hospital

Liuchow, Guangxi, 545006, China

Location

He'nan Provincial Hospital of Infectious Disease (Zhengzhou Municipal Sixth People's Hospital)

Zhengzhou, He'nan, 450015, China

Location

Huazhong University of Science and Technology Affiliated Tongji Hospital

Wuhan, Hubei, 430030, China

Location

Nanjing Municipal Second Hospital

Nanjing, Jiangsu, 210003, China

Location

Jilin University First Hospital

Changchun, Jilin, 130021, China

Location

Yanbian University Affiliated Hosptial

Yanbian, Jilin, 133000, China

Location

Shenyang Municipal Sixth People's Hospital

Shenyang, Liaoning, 110006, China

Location

Chinese PLA Fourth Military Medical University Tangdu Hospital

Xi'an, Shaanxi, 710038, China

Location

Ji'nan Municipal Hospital of Infectious Disease

Ji'nan, Shandong, 250021, China

Location

Sichuan Provincial People's Hospital

Chengdu, Sichuan, 610072, China

Location

Xinjiang Uygur Autonomous Region Traditional Chinese Medicine Hospital

Ürümqi, Xinjiang, 830000, China

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

Sofosbuvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Uridine Monophosphate; Uracil Nucleotides; Pyrimidine Nucleotides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleotides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleotides

Study Officials

• Junqi Niu, M.D.

  First Hospital of Jilin Univerisity

  PRINCIPAL INVESTIGATOR

• Lai Wei, M.D.

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single-arm, external (historic) control

Study Record Dates

• First Submitted: June 20, 2019
• First Posted: June 24, 2019
• Study Start: June 7, 2017
• Primary Completion: January 25, 2018
• Study Completion: March 7, 2018
• Last Updated: June 25, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (19)