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

August 11, 2016 updated by: Qin Ning, Tongji Hospital

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)

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Anticipated)

300

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Beijing
      • Beijing, Beijing, China, 100069
        • Recruiting
        • Beijing YouAn Hospital
        • Contact:
        • Contact:
          • Yali Liu, Doctor
          • Phone Number: 86 13260255331
          • Email: xxbi@163.com
        • Principal Investigator:
          • Xinyue Chen, Doctor
    • Hubei
      • Wuhan, Hubei, China, 430030
        • Recruiting
        • Tongji Hospital
        • Contact:
        • Contact:
        • Principal Investigator:
          • Qin Ning, Doctor
    • Hunan
      • Changsha, Hunan, China, 410008
        • Recruiting
        • Xiangya Hospital, Central South University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Deming Tan, Doctor
    • Zhejiang
      • Wenzhou, Zhejiang, China, 325000
        • Recruiting
        • The First Affiliated Hospital of Wenzhou Medical University
        • Contact:
        • Contact:
        • Principal Investigator:
          • Yongping Chen, Doctor

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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: 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 Names:
  • ETV and or ADV
Drug: Y peginterferon alfa-2b
In arm 2 and 3, Y peginterferon alfa-2b is used for 96 weeks
Other Names:
  • peginterferon alfa-2b
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: 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 Names:
  • ETV and or ADV
Drug: Y peginterferon alfa-2b
In arm 2 and 3, Y peginterferon alfa-2b is used for 96 weeks
Other Names:
  • peginterferon alfa-2b
Drug: Granulocyte-macrophage colony stimulating factor
In arm 3, Granulocyte-macrophage colony stimulating factor is used for 48 weeks intermittently
Other Names:
  • GMCSF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of HBsAg loss at week 96
Time Frame: week 96
Change from baseline in Percentage of HBsAg loss at week 96
week 96

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from baseline in HBsAg quantification and HBsAg decline at week 96
Time Frame: week 96
HBsAg quantification and HBsAg decline from baseline are measured.
week 96
Change from baseline in HBsAg seroconversion at week 96
Time Frame: week 96
HBsAg seroconversion from baseline is measured.
week 96

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of HBeAg loss or HBeAg seroconversion at week 96 for HBeAg positive patients
Time Frame: week 96
Percentage of HBeAg loss or HBeAg seroconversion are measured at week 96 for patients with HBeAg positive at baseline
week 96
Percentage of HBV DNA normalization and ALT normalization at week 96
Time Frame: week 96
Percentage of HBV DNA normalization and ALT normalization at week 96 are measured.
week 96
Percentage of sustained virology response at week 120
Time Frame: week 120
Sustained virology response is measure at follow up week 24
week 120

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tongji Hospital

Collaborators

Xiamen Amoytop Biotech Co., Ltd.

Investigators

  • Principal Investigator: Qin Ning, Doctor, Department of Infectious Diseases, Tongji Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Anticipated)

December 1, 2018

Study Completion (Anticipated)

June 1, 2019

Study Registration Dates

First Submitted

November 23, 2014

First Submitted That Met QC Criteria

December 23, 2014

First Posted (Estimate)

December 30, 2014

Study Record Updates

Last Update Posted (Estimate)

August 15, 2016

Last Update Submitted That Met QC Criteria

August 11, 2016

Last Verified

August 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Anchor study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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