Safety and Efficacy of KW-136 and Sofosbuvir for Treatment of Chronic Hepatitis C

NCT03416491 | Completed Phase 2

• 2 other identifiers: BJKY-2016-006CTR20170073
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 12

Brief Summary

This study aimed to evaluate the safety and efficacy of KW-136, an investigational anti-hepatitis C virus (HCV) drug, combined with sofosbuvir for treatment of Chinese adults chronically infected with HCV. Thirty (30) non-cirrhotic subjects were medicated with KW-136 30 mg daily, 60 non-cirrhotic subjects with KW-136 60 mg daily, and 30 cirrhotic subjects with KW-136 60 mg daily; all the 120 subjects received sofosbuvir 400 mg daily. The treatment course lasted 12 successive weeks and thereafter all the study participants entered into a 12-week treatment-free follow-up period.

Conditions

Hepatitis C, Chronic

Keywords

Chronic hepatitis C; Hepatitis C virus; KW-136; sofosbuvir; nonstructural protein 5A; nonstructural protein 5B; panogentypic regimen

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 (2)

• Virologic breakthrough

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

• Virologic relapse

  4 and 12 weeks after end of treatment

Study Arms (3)

NC_30

EXPERIMENTAL

Non-cirrhotic subjects were medicated with KW-136 capsules 30 mg once daily and fixed-dose (400 mg once daily) sofosbuvir tablets for 12 successive weeks.

Drug: KW-136; Drug: Sofosbuvir

NC_60

EXPERIMENTAL

Non-cirrhotic 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; Drug: Sofosbuvir

LC_60

EXPERIMENTAL

Cirrhotic 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; Drug: Sofosbuvir

Interventions

KW-136 DRUG

KW-136 30 mg was provided in 3 capsules, 10 mg each, and KW-136 60 mg in a single capsule of 60 mg.

Also known as: Coblopasvir

LC_60; NC_30; NC_60

Sofosbuvir DRUG

Sofosbuvir was provided in a single tablet of 400 mg.

LC_60; NC_30; NC_60

Eligibility Criteria

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

You may qualify if:

• aged between 18 and 65 years (inclusive) at the time of informed consenting and of either sex
• with a body mass index (BMI) between 18 and 30 kg/m\^2 (inclusive)
• chronically infected with HCV, namely, with positive anti-HCV, HCV RNA or genotyping results at least six (6) months before the baseline, or with a liver biopsy confirming chronic hepatitis at most twelve (12) months before the baseline or during the screening period
• anti-HCV positivity and at least once testing result with HCV RNA equaling to or above 10\^4 IU/mL
• genotyped to be gentoype (GT-1) or non-GT-1(including GT-2, 3, 6 or others) by the centralized laboratory
• naive to anti-HCV treatment, defined as being not previously treated with any interferon (including interferon alfa or beta or peginterferon), ribavirin, or other approved, investigational or any other not approved anti-HCV regimens of any source
• with or without cirrhosis (cirrhosis defined as FibroScan liver stiffness modulus (LSM) at least 14.6 kPa on screening, or liver biopsy confirming presence of cirrhosis within twelve (12) months before screening or within screening; no cirrhosis defined as FibroScan LSM below 14.6 kPa or liver biopsy confirming absence of cirrhosis within twelve (12) before screening or within screening; liver biopsy result takes priority over FibroScan LSM)
• women of childbearing potential (including postmenopausal women at or under 50 years of age) with negative blood pregnancy test results; subjects of childbearing potential (including male subjects and their female partners) have no childbearing plan from screening, initiation of treatment until six (6) months after end of treatment and consent to use effective contraceptive measures
• voluntary participation in the study and being able to understand and sign the informed consent form

You may not qualify if:

• having previously used any investigational or experimental direct antiviral agents against HCV, including protease, NS5B polymerase or NS5A inhibitors, before screening
• having received any interferon-based anti-HCV regimens before screening
• having been exposed to any systemic potent immunomodulators , such as steroids or thymosin alfa (excluding use of nasal, inhalational, topical steroids and/or others) for more than two weeks within six (6) months before screening, or anticipated 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; emergence of ascites, upper gastrointestinal bleeding and/or hepatic encephalopathy; with liver function reserve Child-Pugh class B or C
• with primary liver cancer confirmed or evidenced by serum alfa-fetoprotein 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 alaine aminotransferase (ALT) or asparate aminotransferase (AST) above ten (10) times of ULN confirmed on repeated testing
• with white blood cell (WBC) count below 3x10\^9 per liter, neutrophil count below 1.5x10\^9 per liter (or below 1.25x10\^9 per liter for cirrhotics), platelet count below 50x10\^9 per liter, or hemoglobin below 120 g/L (for males) or 110 g/L (for females) confirmed on repeated testing
• with serum creatinine clearance (CLcr) below 50 ml/min using the Cockcroft-Gault formula confirmed on repeated testing
• with uncontrolled diabetes mellitus (hemoglobin A1c\[HbA1c\] above 7.0% 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 screening, history of percutaneous transluminal coronary angioplasty within six (6) months before screening, unstable angina pectoris, QTc interval (Fridericia correction formula QTc = QTxRR\^-1/3) at or above 450 msec or 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)
• with serious kidney diseases (such as chronic kidney disease, kidney insufficiency and others)

Sponsors & Collaborators

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

Study Sites (12)

Peking University People's Hospital

Beijing, Beijing Municipality, 100044, 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

Chinese PLA Third Military Medical University First Affiliated Hospital

Chongqing, Chongqing Municipality, 400038, China

Location

Guangzhou Municipal Eighth People's Hospital

Guanzhou, Guangdong, 510060, China

Location

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

Zhengzhou, He'nan, 450015, China

Location

Nanjing Municipal Second Hospital

Nanjing, Jiangsu, 210003, China

Location

Jilin University First Hospital

Changchun, Jilin, 130021, China

Location

Dalian Municipal Sixth People's Hospital

Dalian, Liaoning, 450015, China

Location

Shenyang Municipal Sixth People's Hospital

Shenyang, Liaoning, 110006, China

Location

Ji'nan Municipal Hospital of Infectious Disease

Ji'nan, Shandong, 250021, China

Location

Qingdao Municipal Hospital

Qingdao, Shandong, 266011, China

Location

Related Publications (1)

• Rao H, Song G, Li G, Yang Y, Wu X, Guan Y, Mao Q, Jiang X, Wang C, Zhang Y, Jia J, Guo X, Li C, Ning J, Qin H, Pan H, Wei L. Safety and efficacy of coblopasvir and sofosbuvir in patients with genotypes 1, 2, 3 and 6 HCV infections without or with compensated cirrhosis. J Viral Hepat. 2020 Jan;27(1):45-51. doi: 10.1111/jvh.13208. Epub 2019 Oct 2.

  PMID: 31520460 DERIVED

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

• Lai Wei, M.D.

  Peking University People's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The centralized laboratory was blinded to treatment assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: parallel, stratified assignment

Study Record Dates

• First Submitted: January 24, 2018
• First Posted: January 31, 2018
• Study Start: February 15, 2017
• Primary Completion: September 17, 2017
• Study Completion: November 8, 2017
• Last Updated: January 31, 2018

Record last verified: 2018-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (12)