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A Prospective Clinical Trial in Chronic Hepatitis B Patients NAs (Nucleotides or Nucleosides) Experienced (Anchor Study)

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2016 by Tongji Hospital
Sponsor:
Collaborator:
Xiamen Amoytop Biotech Co., Ltd.
Information provided by (Responsible Party):
Qin Ning, Tongji Hospital
ClinicalTrials.gov Identifier:
NCT02327416
First received: November 23, 2014
Last updated: August 11, 2016
Last verified: August 2016
  Purpose
This study is a multi-center, randomized, prospective, open-label Phase III Clinical trial to assess the efficacy and safety of combination and sequential treatment with Y peginterferon Alfa-2b,entecavir and GMCSF in chronic hepatitis B patients nucleotides or nucleosides experienced. Patients were randomized to one of 3 groups to receive different antiviral treatment.

Condition Intervention Phase
Hepatitis B, Chronic
Drug: Y peginterferon alfa-2b
Drug: Granulocyte-macrophage colony stimulating factor
Drug: Entecavir and or adefovir dipivoxil
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Prospective Randomized Clinical Trial of Combination Sequential Treatment With Y Peginterferon Alfa-2b and ETV (Entecavir) in CHB (Chronic Hepatitis B) Patients NAs (Nucleotides or Nucleosides) Experienced (Anchor Study)

Resource links provided by NLM:


Further study details as provided by Tongji Hospital:

Primary Outcome Measures:
  • Percentage of HBsAg loss at week 96 [ Time Frame: week 96 ] [ Designated as safety issue: Yes ]
    Change from baseline in Percentage of HBsAg loss at week 96


Secondary Outcome Measures:
  • Change from baseline in HBsAg quantification and HBsAg decline at week 96 [ Time Frame: week 96 ] [ Designated as safety issue: Yes ]
    HBsAg quantification and HBsAg decline from baseline are measured.

  • Change from baseline in HBsAg seroconversion at week 96 [ Time Frame: week 96 ] [ Designated as safety issue: Yes ]
    HBsAg seroconversion from baseline is measured.


Other Outcome Measures:
  • Percentage of HBeAg loss or HBeAg seroconversion at week 96 for HBeAg positive patients [ Time Frame: week 96 ] [ Designated as safety issue: Yes ]
    Percentage of HBeAg loss or HBeAg seroconversion are measured at week 96 for patients with HBeAg positive at baseline

  • Percentage of HBV DNA normalization and ALT normalization at week 96 [ Time Frame: week 96 ] [ Designated as safety issue: Yes ]
    Percentage of HBV DNA normalization and ALT normalization at week 96 are measured.

  • Percentage of sustained virology response at week 120 [ Time Frame: week 120 ] [ Designated as safety issue: Yes ]
    Sustained virology response is measure at follow up week 24


Estimated Enrollment: 300
Study Start Date: October 2014
Estimated Study Completion Date: June 2019
Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1,conventional control group
Drug: Entecavir and or adefovir dipivoxil are used for 96 weeks and the follow up 24 weeks. Entecavir 0.5mg po daily or plus ADV (adefovir dipivoxil)10mg po daily.
Drug: Entecavir and or adefovir dipivoxil
In arm 1, Entecavir and or adefovir dipivoxil are used for 96 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir and or adefovir dipivoxil are used for 48 weeks.
Other Name: ETV and or ADV
Experimental: 2,combination and sequential group
Drug: Y peginterferon Alfa-2b 180 micrograms sc/week for 96 weeks; Drug: Entecavir and or adefovir dipivoxil are used for 48 weeks. Entecavir 0.5mg po daily for 48 weeks or plus ADV 10mg po daily.
Drug: Y peginterferon alfa-2b
In arm 2 and 3, Y peginterferon alfa-2b is used for 96 weeks
Other Name: peginterferon alfa-2b
Drug: Entecavir and or adefovir dipivoxil
In arm 1, Entecavir and or adefovir dipivoxil are used for 96 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir and or adefovir dipivoxil are used for 48 weeks.
Other Name: ETV and or ADV
Experimental: 3, multitarget group
Drug: Y peginterferon Alfa-2b 180 micrograms sc/week for 96 weeks; Drug: Granulocyte-macrophage colony stimulating factor is used for 48 weeks; Drug: Entecavir and or adefovir dipivoxil are used for 48 weeks. Entecavir 0.5mg po daily for 48 weeks or plus ADV 10mg po daily.
Drug: Y peginterferon alfa-2b
In arm 2 and 3, Y peginterferon alfa-2b is used for 96 weeks
Other Name: peginterferon alfa-2b
Drug: Granulocyte-macrophage colony stimulating factor
In arm 3, Granulocyte-macrophage colony stimulating factor is used for 48 weeks intermittently
Other Name: GMCSF
Drug: Entecavir and or adefovir dipivoxil
In arm 1, Entecavir and or adefovir dipivoxil are used for 96 weeks and the follow up 24 weeks as conventional control, In arm 2 and 3, Entecavir and or adefovir dipivoxil are used for 48 weeks.
Other Name: ETV and or ADV

Detailed Description:
Patients who have been pretreated with and responded to one or two nucleotides or nucleosides for at least one year, with HBV (Hepatitis B Virus) DNA less than 1000 copies/ml and HBsAg less 3000 IU/ml were randomized to one of 3 groups, to receive Y peginterferon Alfa-2b 180mcg/week for 96 weeks, entecavir 0.5 mg po daily for 48 weeks plus GMCSF (Granulocyte-macrophage colony stimulating factor) for 48 weeks, or Y peginterferon Alfa-2b 180mcg/week for 96 weeks and entecavir 0.5 mg po daily for 48 weeks, or only ETV for 96 weeks.
  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female patients from 18 to 65 years of age;
  2. HBsAg positive, entecavir and or adefovir dipivoxil are used at least 1 year including patients with nucleotides or nucleoside resistance history if their HBV DNA obtained control;
  3. Before nucleotides or nucleosides treatment, ALT > 2 ULN, HBV DNA >10000 copies/ml,HBsAg positive;
  4. Serum HBV DNA < 1000 copies/ml;
  5. Serum HBsAg < 3000 IU/ml;
  6. HBsAg positive;
  7. Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug;
  8. Absence of cirrhosis confirmed by ultrasonic test;
  9. Agree to participate in the study and sign the patient informed consent.

Exclusion Criteria:

  1. Patients who had NAs resistance and HBV DNA > 1000 copies/ml, or treatment of drugs with IFN longer than 6 months;
  2. Other antiviral, anti-neoplastic or immunomodulatory treatment (including supra physiologic doses of steroids and radiation) 6 months prior to the first dose of randomized treatment (except for 7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment). Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded;
  3. Women with ongoing pregnancy or breast-feeding;
  4. Co-infection with active hepatitis A, hepatitis C, hepatitis D(Those hospitals which have the ability to do the test will do) and/or human immunodeficiency virus (HIV);
  5. ALT >10 ULN;
  6. Evidence of decompensated liver disease (Child-Pugh score > 5 ). Child-Pugh > 5 means, if one of the following 5 conditions are met, the patient has to be excluded:

    one of the following 5 conditions are met, the patient has to be excluded:

    1. Serum albumin < 3.5 g/L;
    2. Prothrombin time > 3 seconds prolonged;
    3. Serum bilirubin > 34 µ mol/L;
    4. History of encephalopathy;
    5. History of variceal bleeding;
    6. Ascites;
  7. History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures, thalassemia);
  8. Signs or symptoms of hepatocellular carcinoma, patients with a value of alpha-fetoprotein > 100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months. Patients with values < 20 ng/mL but > 100 ng/mL may be enrolled, if hepatic neoplasia has been excluded by liver imaging;
  9. Neutrophil count < 1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening;
  10. Hemoglobin < 11.5 g/dL for females and <12.5 g/dL for men;
  11. Serum creatinine level > 1.5 ULN in screening period.
  12. Phosphorus < 0.65 mmol/L;
  13. ANA > 1:100;
  14. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease;
  15. History of a severe seizure disorder or current anticonvulsant use;
  16. History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.);
  17. History of chronic pulmonary disease associated with functional limitation;
  18. Diseases that IFN and Nucleotides or nucleosides are not suitable.
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02327416

Contacts
Contact: Qin Ning 86 27 83662391 qning@vip.sina.com

Locations
China, Beijing
Beijing Youan Hospital Recruiting
Beijing, Beijing, China, 100069
Contact: Xinyue Chen, Doctor    86 13911212398    chenxydoc@163.com   
Contact: Yali Liu, Doctor    86 13260255331    xxbi@163.com   
Principal Investigator: Xinyue Chen, Doctor         
China, Hubei
Tongji Hospital Recruiting
Wuhan, Hubei, China, 430030
Contact: Qin Ning, Doctor    86 27 83662391    qning@vip.sina.com   
Contact: Meifang Han, Doctor    86 27 83662391    hanmeifang@hotmail.com   
Principal Investigator: Qin Ning, Doctor         
China, Hunan
Xiangya Hospital, Central South University Recruiting
Changsha, Hunan, China, 410008
Contact: Deming Tan, Doctor    86 13975886582    dmt3008@163.com   
Contact: Lei Fu, Doctor    86 15084739488    936512615@qq.com   
Principal Investigator: Deming Tan, Doctor         
China, Zhejiang
The First Affiliated Hospital of Wenzhou Medical University Recruiting
Wenzhou, Zhejiang, China, 325000
Contact: Yongping Chen, Doctor    86 13505777281    13505777281@163.com   
Contact: Lanman Xu, Doctor    86 13587646315    13587646315@163.com   
Principal Investigator: Yongping Chen, Doctor         
Sponsors and Collaborators
Tongji Hospital
Xiamen Amoytop Biotech Co., Ltd.
Investigators
Principal Investigator: Qin Ning, Doctor Department of Infectious Diseases, Tongji Hospital
  More Information

Responsible Party: Qin Ning, Director and Chair of Department of Infectious Diseases, Tongji Hospital
ClinicalTrials.gov Identifier: NCT02327416     History of Changes
Other Study ID Numbers: Anchor study 
Study First Received: November 23, 2014
Last Updated: August 11, 2016
Health Authority: China: Ministry of Science and Technology
China: Ministry of Health

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Peginterferon alfa-2b
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Adefovir
Adefovir dipivoxil
Entecavir
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on December 07, 2016