An Exploratory Study of RGT Strategy on Optimal NUC-experienced Patients

September 23, 2015 updated by: Qing XIe, Ruijin Hospital

A Prospective, Randomized, Multicenter, Open-label, Exploratory Study of Utilizing of "Response-Guided-Therapy (RGT)" Strategy on Optimal Nucleoside Analogue (NUC)-Experienced Patients

The aim of current study is to investigate whether the HBsAg clearance rate can be improved if applying RGT((Response-Guided Therapy) strategy in HBeAg positive CHB(chronic hepatitis B) patients treated by nucleoside analogue(NUC) achieved HBVDNA<1000copies/ml,and HBsAg<5000IU/ml; &HBeAg<100PEIU/ml (or470s/co), combined with PEG-IFN a-2a for 24 weeks.

Study Overview

Detailed Description

The current study is a prospective, randomized, open, multi-center investigation. The aim of current study is to investigate whether the HBsAg clearance rate can be improved if applying RGT strategy in HBeAg positive CHB patients treated by NUC achieved HBVDNA<1000copies/ml,and HBsAg<5000IU/ml; &HBeAg<100PEIU/ml (or470s/co), combined with PEG-IFN a-2a for 24 weeks. Then the subjects will be divided into three groups according to qHBsAg levels of week 24 (RGT). For the subjects who qHBsAg<200IU/ml of week 24, they are defined in Group A; the subjects in Group A will continue to be treated by NUC combined with PEG-IFN a-2a 180μg for another 24 weeks(total will be 48 weeks). If the qHBsAg at week 24 did not achieve minor 200IU/ml, the subjects will be randomized to 2 groups: Group B: the subjects will continue to be treated by NUC combined with PEG-IFN a-2a 180μg for another 24 weeks (total will be 48 weeks); Group C: the subjects will be treated by NUC until 48 weeks.

Study Type

Interventional

Enrollment (Anticipated)

324

Phase

  • Phase 4

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 nucleoside analogue(NUC) (except of telbivudine);
  3. Treated with NUC (except of telbivudine)for more than 24 weeks and achieve HBV DNA<1000copies/ml and HBsAg<5000IU/ml;&HBeAg<100PEIU/ml(470s/co);
  4. Without contra-indications to Peginterferon alfa-2a therapy as detailed in the label;
  5. Without co-infection with hepatitis C, hepatitis D and HIV;
  6. Women without ongoing pregnancy or breast feeding and willing to take an effective contraceptive measure during the treatment
  7. Agree to participate in the study and sign the patient informed consent form.

Exclusion criteria

  1. Co-infection with active hepatitis A, hepatitis C, hepatitis D and/or human immunodeficiency virus (HIV)
  2. AFP(alpha fetoprotein)>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:

    • Serum albumin <35 g/L
    • Prothrombin time prolonged≥ 4 seconds or PTA(prothrombin activity) < 60%
    • Serum bilirubin > 34 µmol/L
    • History of encephalopathy
    • 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(absolute neutrophil count)<1.5x 10^9/L or PLT(platelet count)<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(telbivudine) 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
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A:PEG+NUC (HBsAg<200IU/ml at week 24)

Peginterferon alfa-2a 180μg /wk plus nucleoside analogue(NUC):

HBsAg<200IU/ml at week 24 (Following treatment with Peginterferon alfa-2a plus nucleoside analogue(NUC) for 24 weeks)

Peginterferon alfa-2a 180μg /wk plus Entecavir 0.5mg qd for 48 weeks(Arm A and B)
Other Names:
  • Pegasys; ETV
Peginterferon alfa-2a 180μg /wk plus Lamivudine 0.1g qd for 48 weeks(Arm A and B)
Other Names:
  • Pegasys; LAM
Peginterferon alfa-2a 180μg /wk plus Adefovir 10mg qd for 48 weeks(Arm A and B)
Other Names:
  • Pegasys;ADV
Peginterferon alfa-2a 180μg /wk plus Tenofovir 300mg qd for 48 weeks(Arm A and B)
Other Names:
  • Pegasys;TDF
Active Comparator: B:PEG+NUC(HBsAg>200IU/ml at week 24)

Peginterferon alfa-2a 180μg /wk plus+nucleoside analogue(NUC):

HBsAg>200IU/ml at week 24 (Following treatment with Peginterferon alfa-2a plus nucleoside analogue(NUC) for 24 weeks)

Peginterferon alfa-2a 180μg /wk plus Entecavir 0.5mg qd for 48 weeks(Arm A and B)
Other Names:
  • Pegasys; ETV
Peginterferon alfa-2a 180μg /wk plus Lamivudine 0.1g qd for 48 weeks(Arm A and B)
Other Names:
  • Pegasys; LAM
Peginterferon alfa-2a 180μg /wk plus Adefovir 10mg qd for 48 weeks(Arm A and B)
Other Names:
  • Pegasys;ADV
Peginterferon alfa-2a 180μg /wk plus Tenofovir 300mg qd for 48 weeks(Arm A and B)
Other Names:
  • Pegasys;TDF
Active Comparator: C:NUC(HBsAg>200IU/ml at week 24)

nucleoside analogue(NUC):

HBsAg>200IU/ml at week 24 (Following treatment with Peginterferon alfa-2a plus nucleoside analogue(NUC) for 24 weeks)

Entecavir 0.5mg qd for 24 weeks(Arm C)
Other Names:
  • ETV
Lamivudine 0.1g qd for 24 weeks(Arm C)
Other Names:
  • LAM
Adefovir 10mg qd for 24 weeks(ArmC)
Other Names:
  • Adefovir dipivoxil;ADV
Tenofovir 300mg qd for 24 weeks(Arm C)
Other Names:
  • Tenofovir disoproxil;TDF

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who achieve HBsAg clearance
Time Frame: Week 48
To investigate whether HBsAg clearance rate can be improved at week 48 following applying RGT strategy(week 24) in NUC-experience subjects will be measured by the number of participants who achieve HBsAg clearance
Week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of participants who achieve HBsAg seroconversion
Time Frame: Week 48
To investigate the HBsAg seroconversion rate at week 48 can be improved following applying RGT strategy in NUC-experience subjects will be measured by the number of participants who achieve HBsAg seroconversion
Week 48
Number of participants who achieve HBeAg loss
Time Frame: Week 48
To investigate the HBeAg loss rate at week 48 can be improved following applying RGT strategy in NUC-experience subjects will be measured by the number of participants who achieve HBeAg loss
Week 48
Number of participants who achieve HBeAg seroconversion
Time Frame: Week 48
To investigate the HBeAg seroconversion rate at week 48 will be improved following applying RGT strategy in NUC-experience subjects will be measured by the number of participants who achieve HBeAg seroconversion
Week 48
Percentage of of participants who achieve HBsAg decline >2log from baseline(0 week)
Time Frame: Week 48
To investigate HBsAg decline from baseline at week 48 following applying RGT strategy in NUC-experience subjects by measured the percentage of of participants who achieve HBsAg decline>2log from baseline(0 week)
Week 48
Percentage of of participants who achieve HBsAg <10IU/mL
Time Frame: Week 48
To investigate the percentage of of participants who achieve HBsAg <100IU/mLat week 48 following applying RGT strategy in NUC-experience subjects
Week 48
Percentage of of participants who achieve combined response(defined as HBeAg seroconversion and HBVDNA<300copies/mL)
Time Frame: Week 48
To investigate the percentage of of participants who achieve combined response at week 48 following applying RGT strategy in NUC-experience subjects will be measured by number of participants who achieve combined response
Week 48
Percentage of of participants who achieve dural response I (defined as HBeAg seroconversion and HBsAg<100IU/mL)
Time Frame: Week 48
To investigate the percentage of of participants who achieve dural response I at week 48 following applying RGT strategy in NUC-experience subjects will be measured by number of participants who achieve dural response
Week 48
Percentage of of participants who achieve dural response II (defined as HBeAg seroconversion and HBsAg<10IU/mL)
Time Frame: Week 48
To investigate the percentage of of participants who achieve dural response II at week 48 following applying RGT strategy in NUC-experience subjects will be measured by number of participants who achieve dural response
Week 48
Number of participants who relapses (HBVDNA>1000copies/ml)
Time Frame: Week 48
To investigate the number of participants who relapses following applying RGT strategy in NUC-experience subjects
Week 48
Number of Participants with AE
Time Frame: Week 48
Number of participants with adverse events as a measure of safety and tolerability
Week 48
Number of Participants with SAE
Time Frame: Week 48
Number of participants with SAEs as a measure of safety and tolerability
Week 48

Collaborators and Investigators

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

Sponsor

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.

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

May 1, 2015

Primary Completion (Anticipated)

August 1, 2016

Study Completion (Anticipated)

February 1, 2017

Study Registration Dates

First Submitted

September 22, 2015

First Submitted That Met QC Criteria

September 23, 2015

First Posted (Estimate)

September 25, 2015

Study Record Updates

Last Update Posted (Estimate)

September 25, 2015

Last Update Submitted That Met QC Criteria

September 23, 2015

Last Verified

September 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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