ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety and Efficacy of Generic Sofosbuvir and Ribavirin for Treatment-naive Genotype 2 Chronic Hepatitis C (SOF_GT2)

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: NCT03453346
Recruitment Status : Completed
First Posted : March 5, 2018
Last Update Posted : March 7, 2018
Sponsor:
Collaborator:
KawinGreen Biotech Co., Ltd.
Information provided by (Responsible Party):
Kawin Technology Share-holding Co., Ltd.

Brief Summary:
This study aimed to evaluate the safety and efficacy of generic sofosbuvir, an investigational anti-hepatitis C virus (HCV) drug, combined with weight-adjusted ribavirin for treatment-naive Chinese adults chronically infected with genotype 2 HCV, the second most prevalent genotype in China. One hundred and thirty-two (132) subjects, including one hundred and twenty (120) non-cirrhotics and twelve (12) compensatory cirrhotics, were medicated with sofosbuvir 400 mg daily combined with weight-adjusted ribavirin 1000-1200 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.

Condition or disease Intervention/treatment Phase
Hepatitis C, Chronic Hepatitis C Virus Infection, Response to Therapy of Drug: Sofosbuvir Drug: Ribavirin Not Applicable

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. Genotype 2 HCV is reported to be the second most common type (~25%) in Chinese population and associated with a high risk of acute liver disease exacerbation and other extrahepatic diseases. Sofosbuvir is a pan-genotypic HCV ribonucleic acid (RNA) polymerase inhibitor directing at HCV RNA replication. Genotype 2 chronic hepatitis C has a high treatment response to the combined regimen of peginterferon and weight-adjusted ribavirin. The all-oral combination regimen of sofosbuvir and ribavirin is expected to completely suppress genotype 2 HCV replication in subjects chronically infected with HCV and achieve a sustained virologic response, namely, HCV not detected or below a predefined limit in plasma, 12 or 24 weeks after cessation of treatment.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 136 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Open label, single arm, historical control
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Evaluation of Safety and Efficacy of Generic Sofosbuvir and Ribavirin for Treatment-naive Adults Chronically Infected With Genotype 2 Hepatitis C Virus: an Open-label, Multicenter Confirmatory Study
Actual Study Start Date : August 5, 2016
Actual Primary Completion Date : March 18, 2017
Actual Study Completion Date : March 30, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Noncirrhotic and cirrhotic GT-2
Generic sofosbuvir tablet 400 mg once daily plus weight-adjusted ribavirin tablet (1000 mg for <75 kg, and 1200 mg for >=75 kg) twice daily with meal, orally given, for 12 successive weeks
Drug: Sofosbuvir
Generic sofosbuvir tablet 400 mg
Other Name: SOF

Drug: Ribavirin
Ribavirin was provided in 100-mg tablets.
Other Name: RBV




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. 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

  2. Virologic relapse [ Time Frame: 4 and 12 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • aged between 18 and 65 years (inclusive) and of either sex
  • with a body mass index (BMI) between 18 and 30 kg/m^2
  • chronically infected with genotype 2 HCV, and the diagnosis of chronic hepatitis C consistent with the Chinese Guideline for Prevention and Management of Hepatitis C
  • HCV RNA equaling to or above 10^4 IU/mL and anti-HCV positivity
  • 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, presence or absence of which must be documented as at lease one item of the following: 1) liver biopsy confirming presence (e.g., Metavir score = 4 or Ishak score >=5) or absence of cirrhosis within twelve (12) months before screening; 2) FibroScan showing cirrhosis (liver stiffness modulus [LSM]>=12.5 kPa) or no cirrhosis (LSM=<9.6 kPa); 3) a subject with a LSM of 9.6-12.5 kPa (exclusive) could only be enrolled when the liver biopsy confirmed or excluded presence of cirrhosis
  • women of childbearing potential without a history of menopause and with a negative blood pregnancy test; subjects of childbearing potential (including male subjects and their female partners) had no childbearing plan from screening, initiation of treatment until six (6) months after the end of treatment and consented to use effective contraceptive measures
  • voluntary participation in the study and being able to understand and sign the informed consent form

Exclusion Criteria:

  • being infected with mixed-genotype HCV
  • having previously used any investigational or experimental direct antiviral agents against HCV, including protease, nonstructural (NS) protein 5B 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 (2) weeks within six (6) months before screening, or anticipated to be exposed to these agents during the study period
  • being coinfected with hepatitis B virus (HBV) or human immunodeficient virus (HIV)
  • 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%; 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 (anti-nuclear antibody[ANA] titer above 1:100), Wilson disease or hemochromatosis
  • with serum alaine aminotransferase (ALT) or asparate aminotransferase (AST) above ten (10) times of ULN
  • with white blood cell (WBC) count below 3x10^9 per liter, neutrophil count below 1.5x10^9 per liter, platelet count below 50x10^9 per liter, or hemoglobin below the lower limit of the normal
  • with serum creatinine clearance (CLcr) below 50 ml/min using the Cockcroft-Gault formula
  • with uncontrolled diabetes mellitus (hemoglobin A1c[HbA1c] above 7.0%)
  • 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, or any uncontrolled arrhythmias
  • 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 screening
  • with a history of major organ transplantation
  • being known to be severely hypersensitive or allergic to any drugs, especially the testing medications and other constituents
  • with a history of active alcohol or drug abuse
  • being pregnant or lactating
  • being unable to discontinue prohibited medications as defined by the protocol
  • having participated in any other clinical studies within three (3) months before screening
  • being unable or unwilling to provide informed consent or unable to follow the protocol requirements
  • any other conditions of excluding a potential participant 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): NCT03453346


Locations
China, Beijing
Chinese PLA 302 Hospital
Beijing, Beijing, China, 100039
Peking University People's Hospital
Beijing, Beijing, China, 100044
Capital Medical University Affiliated Beijing Youyi Hospital
Beijing, Beijing, China, 100050
Capital Medical University Affiliated Beijing You'an Hospital
Beijing, Beijing, China, 100069
Capital Medical University Affiliated Beijing Ditan Hospital
Beijing, Beijing, China, 100102
China, Chongqing
Chongqing Medical University Affiliated Second Hospital
Chongqing, Chongqing, China, 400010
Chinese PLA Third Military Medical University First Affiliated Hospital
Chongqing, Chongqing, China, 400038
China, Hebei
Hebei Medical University Affiliated Third Hospital
Shijiazhuang, Hebei, China, 50051
China, Henan
He'nan Provincial People's Hospital
Zhengzhou, Henan, China, 450003
He'nan Provincial Hospital of Infectious Disease (Zhengzhou Municipal Sixth People's Hospital)
Zhengzhou, Henan, China, 450015
China, Jiangsu
Nanjing Municipal Second Hospital
Nanjing, Jiangsu, China, 210003
China, Jilin
Jilin University First Hospital
Changchun, Jilin, China, 130021
China, Liaoning
Shenyang Municipal Sixth People's Hospital
Shenyang, Liaoning, China, 110006
China, Shaanxi
Chinese PLA Fourth Military Medical University Tangdu Hospital
Xi'an, Shaanxi, China, 710038
Xi'an Jiaotong University College of Medicine Affiliated First Hospital
Xi'an, Shaanxi, China, 710061
China, Shandong
Qingdao Municipal Hospital
Qingdao, Shandong, China, 266011
China, Sichuan
Sichuan Provincial People's Hospital
Chengdu, Sichuan, China, 610072
Sponsors and Collaborators
Kawin Technology Share-holding Co., Ltd.
KawinGreen Biotech Co., Ltd.
Investigators
Principal Investigator: Lai Wei, M.D. Peking University People's Hospital

Responsible Party: Kawin Technology Share-holding Co., Ltd.
ClinicalTrials.gov Identifier: NCT03453346     History of Changes
Other Study ID Numbers: BJKY-2016-003
CTR20160399 ( Registry Identifier: China Drug Trials )
First Posted: March 5, 2018    Key Record Dates
Last Update Posted: March 7, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No IPD sharing plan was included in the study protocol.

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.:
Hepatitis C virus
Sofosbuvir
RNA polymerase inhibitor
Ribavirin
Genotype 2
Sustained virologic response
Confirmatory study

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Virus Diseases
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Ribavirin
Sofosbuvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents