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KW-136 With Sofosbuvir for Chinese Adults With Chronic Hepatitis C (KW-136_III)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03995485
Recruitment Status : Completed
First Posted : June 24, 2019
Last Update Posted : June 25, 2019
Sponsor:
Collaborator:
KawinGreen Biotech Co., Ltd.
Information provided by (Responsible Party):
Kawin Technology Share-holding Co., Ltd.

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.

Condition or disease Intervention/treatment Phase
Hepatitis C, Chronic Drug: KW-136 capsule Drug: Sofosbuvir Phase 3

Detailed Description:

It is estimated that China has a population of over 10 million infected with HCV and also a highly variable HCV genotype geographic distribution. A simple, universal, non-genotype-specific treatment regimen is preferred for anti-HCV treatment in clinical practice and public health. KW-136 and sofosbuvir are potent anti-HCV agents targeting at different HCV proteins, namely, nonstructural protein 5A and 5B, respectively. The combination regimen of KW-136 and sofosbuvir is expected to completely suppress HCV replication in subjects chronically infected with HCV and achieve a sustained virologic response (SVR12), namely, HCV not detected or below a predefined limit in plasma, 12 or 24 weeks after cessation of treatment.

In a previous phase 2 exploratory study, an all-oral, ribavirin-free regiment of KW-136, an investigational HCV NS5A inhibitor, combined with sofosbuvir, demonstrated a ~99% SVR12 in treatment-naive adult subjects chronically infected with major genotypes of HCV found in China, including those with compensatory cirrhosis. This phase 3 study aimed to confirm the efficacy and safety of this combined regimen in a large scale of target patient population, including interferon-experienced subjects. This simple, uniform regimen is expected to be the solution to HCV eradication in China from the perspective of public health.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 371 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Single-arm, external (historic) control
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Efficacy and Safety of KW-136 Capsule Combined With Sofosbuvir Tablet for Treatment of Adult Chronic Hepatitis C: an Open-label, Multi-center, Phase 3 Study
Actual Study Start Date : June 7, 2017
Actual Primary Completion Date : January 25, 2018
Actual Study Completion Date : March 7, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Sofosbuvir

Arm Intervention/treatment
Experimental: KW-136+SOF
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
KW-136 60 mg was provided in a single capsule of 60 mg.
Other Name: Coblopasvir

Drug: Sofosbuvir
Sofosbuvir was provided in a single tablet of 400 mg.




Primary Outcome Measures :
  1. Sustained virologic response at 12 weeks after end of treatment (SVR12) [ Time Frame: 12 weeks after end of treatment ]
    Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)


Secondary Outcome Measures :
  1. Sustained virologic response at 4 weeks after end of treatment (SVR4) [ Time Frame: 4 weeks after end of treatment ]
    Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)

  2. Rapid virologic response at 1 week after initiation of treatment (RVR1) [ Time Frame: 1 week after initiation of treatment ]
    Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)

  3. Rapid virologic response at 2 weeks after initiation of treatment (RVR2) [ Time Frame: 2 weeks after initiation of treatment ]
    Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)

  4. Rapid virologic response at 4 weeks after initiation of treatment (RVR4) [ Time Frame: 4 weeks after initiation of treatment ]
    Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)

  5. Rapid virologic response at 8 weeks after initiation of treatment (RVR8) [ Time Frame: 8 weeks after initiation of treatment ]
    Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)

  6. Rapid virologic response at 12 weeks after initiation of treatment (RVR12) [ Time Frame: 12 weeks after initiation of treatment ]
    Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)


Other Outcome Measures:
  1. Sustained virologic response at 24 weeks after end of treatment (SVR24) [ Time Frame: 24 weeks after end of treatment ]
    Percentage of subjects with plasma HCV not detected or below the lower limit of quantitation (15 IU/mL)

  2. Virologic breakthrough [ Time Frame: 2, 4, 8 and 12 weeks after initiation of treatment ]
    Percentage of subjects with on-treatment re-detected plasma HCV RNA after HCV RNA below the lower limit of quantitation

  3. Virologic relapse [ Time Frame: 4,12 and 24 weeks after end of treatment ]
    Percentage of subjects with off-treatment re-detected plasma HCV RNA after end-of-treatment HCV RNA below the lower limit of quantitation



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • with serious kidney diseases, such as chronic kidney disease, kidney insufficiency and others
  • with serious gastrointestinal disorders, such as peptic ulcer, colitis and others
  • with serious respirator disorders, such as active pulmonary tuberculosis, lung infection, chronic obstructive pulmonary disease, pulmonary interstitial disease and others
  • with active or suspected malignant tumors, or with a previous history of malignant tumors, excluding skin basal cell carcinoma or cervical carcinoma in situ, within five (5) years before the screening
  • with a history of major organ transplantation
  • with a hypersensitive predisposition or a known history of serious allergy, especially to the investigational products and substances
  • with a history of active alcohol or drug abuse within six (6) months before the screening
  • pregnant women or lactating women rejecting or unable to discontinue nursing
  • being unable to discontinue prohibited medications as defined by the protocol
  • having previously participated in clinical studies of any other drugs within three (3) months before the screening
  • being unable or unwilling to provide informed consent, or unable to follow the protocol requirements
  • with any other conditions of ineligibility at the discretion of the investigators

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03995485


Locations
Show Show 19 study locations
Sponsors and Collaborators
Kawin Technology Share-holding Co., Ltd.
KawinGreen Biotech Co., Ltd.
Investigators
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Principal Investigator: Junqi Niu, M.D. First Hospital of Jilin Univerisity
Principal Investigator: Lai Wei, M.D. Peking University People's Hospital

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Responsible Party: Kawin Technology Share-holding Co., Ltd.
ClinicalTrials.gov Identifier: NCT03995485    
Other Study ID Numbers: KYGL-2017-001
CTR20171654 ( Registry Identifier: China Drug Trials )
First Posted: June 24, 2019    Key Record Dates
Last Update Posted: June 25, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No IPD plan is included in the study protocol.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Kawin Technology Share-holding Co., Ltd.:
Chronic hepatitis C
Hepatitis C virus
Eradication
KW-136
Sofosbuvir
Nonstructural protein 5A
Nonstructural protein 5B
Panogentypic regimen
Confirmatory study
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Sofosbuvir
Antiviral Agents
Anti-Infective Agents