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

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ClinicalTrials.gov Identifier: NCT02560649
Recruitment Status : Unknown
Verified September 2015 by Qing XIe, Ruijin Hospital.
Recruitment status was:  Active, not recruiting
First Posted : September 25, 2015
Last Update Posted : September 25, 2015
Sponsor:
Information provided by (Responsible Party):
Qing XIe, Ruijin Hospital

Tracking Information
First Submitted Date  ICMJE September 22, 2015
First Posted Date  ICMJE September 25, 2015
Last Update Posted Date September 25, 2015
Study Start Date  ICMJE May 2015
Estimated Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 23, 2015)
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
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2015)
  • 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
  • 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
  • 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
  • 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)
  • 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
  • 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
  • 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
  • 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
  • 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
  • Number of Participants with AE [ Time Frame: Week 48 ]
    Number of participants with adverse events as a measure of safety and tolerability
  • Number of Participants with SAE [ Time Frame: Week 48 ]
    Number of participants with SAEs as a measure of safety and tolerability
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE An Exploratory Study of RGT Strategy on Optimal NUC-experienced Patients
Official Title  ICMJE A Prospective, Randomized, Multicenter, Open-label, Exploratory Study of Utilizing of "Response-Guided-Therapy (RGT)" Strategy on Optimal Nucleoside Analogue (NUC)-Experienced Patients
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis B
Intervention  ICMJE
  • Drug: Peginterferon alfa-2a plus Entecavir
    Peginterferon alfa-2a 180μg /wk plus Entecavir 0.5mg qd for 48 weeks(Arm A and B)
    Other Name: Pegasys; ETV
  • Drug: Peginterferon alfa-2a plus Lamivudine
    Peginterferon alfa-2a 180μg /wk plus Lamivudine 0.1g qd for 48 weeks(Arm A and B)
    Other Name: Pegasys; LAM
  • Drug: Peginterferon alfa-2a plus Adefovir
    Peginterferon alfa-2a 180μg /wk plus Adefovir 10mg qd for 48 weeks(Arm A and B)
    Other Name: Pegasys;ADV
  • Drug: Peginterferon alfa-2a plus Tenofovir
    Peginterferon alfa-2a 180μg /wk plus Tenofovir 300mg qd for 48 weeks(Arm A and B)
    Other Name: Pegasys;TDF
  • Drug: Entecavir
    Entecavir 0.5mg qd for 24 weeks(Arm C)
    Other Name: ETV
  • Drug: Lamivudine
    Lamivudine 0.1g qd for 24 weeks(Arm C)
    Other Name: LAM
  • Drug: Adefovir
    Adefovir 10mg qd for 24 weeks(ArmC)
    Other Name: Adefovir dipivoxil;ADV
  • Drug: Tenofovir disoproxil
    Tenofovir 300mg qd for 24 weeks(Arm C)
    Other Name: Tenofovir disoproxil;TDF
Study Arms  ICMJE
  • 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)

    Interventions:
    • Drug: Peginterferon alfa-2a plus Entecavir
    • Drug: Peginterferon alfa-2a plus Lamivudine
    • Drug: Peginterferon alfa-2a plus Adefovir
    • Drug: Peginterferon alfa-2a plus Tenofovir
  • 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)

    Interventions:
    • Drug: Peginterferon alfa-2a plus Entecavir
    • Drug: Peginterferon alfa-2a plus Lamivudine
    • Drug: Peginterferon alfa-2a plus Adefovir
    • Drug: Peginterferon alfa-2a plus Tenofovir
  • 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)

    Interventions:
    • Drug: Entecavir
    • Drug: Lamivudine
    • Drug: Adefovir
    • Drug: Tenofovir disoproxil
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: September 23, 2015)
324
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE February 2017
Estimated Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02560649
Other Study ID Numbers  ICMJE PYRAMID
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Qing XIe, Ruijin Hospital
Study Sponsor  ICMJE Ruijin Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Ruijin Hospital
Verification Date September 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP