Combined Therapy With Peginterferon Alfa-2a With NA in NA-treated HBeAg Positive Patients

December 2, 2015 updated by: Qing XIe, Ruijin Hospital

A Prospective, Randomized, Multicenter, Open-label Study Evaluating HBeAg Seroconversion in HBeAg Positive CHB Patients on Treatment With NA Switched to Combined Therapy With Peginterferon Alfa-2a and NA for 48 Weeks

This is a prospective, randomized, multicenter, open-label study. After more than 24 weeks NA treatment, HBeAg positive CHB patients who achieved HBV DNA<1000copies/ml but HBeAb negative, will be randomized (1:1) into 2 study arms as follows:

Arm A: Peginterferon alfa-2a 180μg /wk plus NA 1 piece qd for 48 weeks Arm B: Entecavir 0.5mg qd for 48 weeks

Study Overview

Detailed Description

This is a prospective, randomized, multicenter, open-label study. After more than 24 weeks NA treatment, HBeAg positive CHB patients who achieved HBV DNA<1000copies/ml but HBeAb negative, will be randomized (1:1) into 2 study arms as follows:

Arm A: Peginterferon alfa-2a 180μg /wk plus NA 1piece qd for 48 weeks Arm B:NA 1 piece qd for 48 weeks

The primary endpoint: HBeAg seroconversion at week 48

Study Type

Interventional

Enrollment (Anticipated)

366

Phase

  • Phase 4

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

      • Guilin, China
        • Recruiting
        • The Third People's Hospital of Guilin
        • Contact:
          • Shuquan Chen, doctor
      • Shanghai, China
        • Recruiting
        • Ruijin Hospital
        • Contact:
          • Qing Xie, doctor
        • Contact:
          • Wei Cai, doctor
      • Shanghai, China
        • Recruiting
        • Shanghai Public Health Clinical Center
        • Contact:
          • Liang 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 with age ≥18 and ≤65 years;
  2. There should be evidences that HBsAg and HBeAg have been positive for more than 6 months with HBsAb and HBeAb negative before treated with Entecavir;
  3. Treated with NA for more than 24 weeks and achieve HBV DNA<1000copies/ml with HBeAb negative;
  4. Women without ongoing pregnancy or breast feeding and willing to take an effective contraceptive measure during the treatment
  5. Agree to participate in the study and sign the patient informed consent.

Exclusion Criteria:

  1. Co-infection with active hepatitisA, hepatitisC, hepatitisD and/or human immunodeficiency virus (HIV)
  2. AFP>50ng/ml and/or evidence of hepatocellular carcinoma
  3. Evidence of decompensated liver disease (Child-Pugh scores >5). Child-Pugh >5 means that, if one of the following 6 conditions is met, the patient has to be excluded:

    1. Serum albumin <35 g/L;
    2. Prothrombine time prolonged≥ 4 seconds or PTA < 60%;
    3. Serum bilirubin > 34 µmol/L;
    4. History of encephalopathy;
    5. Ascites
  4. 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)
  5. Pregnant or breast-feeding Women
  6. ANC<1.5x 10^9/L or PLT<90x 10^9/L
  7. Consuming alcohol in excess of 20g/day for women and 30g/day for men within 6 months prior to enrollment
  8. History of severe psychiatric disease, especially depression. Severe psychiatric disease is defined as major depression or psychosis that treated with antidepressant medication or a major tranquilizer at therapeutic doses respectively at any time prior to 3 months or any history of the following: a suicidal attempt hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease
  9. History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.)
  10. History of esophageal varices bleeding or other evidence of esophageal varices bleeding or other symptoms consistent with decompensated liver disease
  11. History of chronic pulmonary disease associated with functional limitation
  12. History of severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases)
  13. Hemodialysis patients or patients with renal insufficiency
  14. History of a severe seizure disorder or current anticonvulsant use
  15. Major organ transplantation or other evidence of severe illness, malignancy, or any other conditions, which would make the patient, in the opinion of the investigator, unsuitable for the study
  16. History of thyroid disease poorly controlled on prescribed medications
  17. Evidence of severe retinopathy or clinically relevant ophthalmologic disorder
  18. History of other severe disease or evidence of other severe disease or any other illness or conditions that the investigator believe that patients are not suitable to join in the study
  19. Immunomodulatory treatment (including interferon) or LDT within 1 year prior to the first dose of treatment
  20. Patients included in another trial or having been given investigational drugs within 12 weeks prior to screening

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
Experimental: PegINF plus nucleos(i)de analgoue
Peginterferon alfa-2a 180μg /wk plus nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks
Peginterferon alfa-2a 180ug/wk s.c for 48 weeks
Other Names:
  • Pegasys
nucleos(t)ide analgoue (NA) 1 piece p.o for 48 weeks
Active Comparator: nucleos(t)ide analgoue
nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks
nucleos(t)ide analgoue (NA) 1 piece p.o for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who achieve HBeAg seroconversion
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the HBeAg seroconversion in HBeAg positive CHB patients on treatment with Entecavir and with HBV DNA <1000copies/ml which will be measured by the number of participants who achieve HBeAg seroconversion
at week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who achieve HBeAg loss
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBeAg seroconversion which will be measured by number of participants who achieve HBeAg loss
at week 48
Number of participants who achieve HBsAg loss
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg loss which will be measured by number of participants who achieve HBsAg loss
at week 48
Number of participants who achieve HBsAg seroconversion
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg seroconversion which will be measured by number of participants who achieve HBsAg seroconversion
at week 48
HBsAg decline from baseline
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve HBsAg decline from baseline
at week 48
Percentage of participants who achieve HBsAg <1000IU/mL
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the percentage of participants who achieve HBsAg<1000IU/mL
at week 48
Percentage of of participants who achieve HBsAg <100IU/mL
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the percentage of of participants who achieve HBsAg<100IU/mL
at week 48
Number of participants who achieve combined response I (defined as HBeAg seroconversion and HBV DNA<100000copies/mL)
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the combined response I which will be measured by number of participants who achieve combined response I
at week 48
Number of participants who achieve combined response II (defined as HBeAg seroconversion and HBV DNA<1000copies/mL)
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the combined response II which will be measured by number of participants who achieve combined response II
at week 48
Number of participants who achieve dural response I (defined as HBeAg seroconversion and HBsAg<1000IU/mL)
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the dural response I which will be measured by number of participants who achieve dural response I
at week 48
Number of participants who achieve dural response II (defined as HBeAg seroconversion and HBsAg<100IU/mL)
Time Frame: at week 48
To investigate whether the combined therapy with Peginterferon alfa-2a with Entecavir can improve the dural response II which will be measured by number of participants who achieve dural response II
at week 48
Number of Participants with AE
Time Frame: at week 48
Number of participants with adverse events as a measure of safety and tolerability
at week 48
Number of Participants with SAE
Time Frame: at week 48
Number of participants with SAEs as a measure of safety and tolerability
at week 48

Collaborators and Investigators

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

Sponsor

Investigators

  • Study Chair: Qing Xie, Ruijin 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

August 1, 2014

Primary Completion (Anticipated)

December 1, 2017

Study Completion (Anticipated)

December 1, 2017

Study Registration Dates

First Submitted

March 25, 2015

First Submitted That Met QC Criteria

June 12, 2015

First Posted (Estimate)

June 17, 2015

Study Record Updates

Last Update Posted (Estimate)

December 3, 2015

Last Update Submitted That Met QC Criteria

December 2, 2015

Last Verified

June 1, 2015

More Information

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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