Overview

This trial is active, not recruiting.

Condition chronic hepatitis b
Treatments peginterferon alfa-2a plus entecavir, peginterferon alfa-2a plus lamivudine, peginterferon alfa-2a plus adefovir, peginterferon alfa-2a plus tenofovir, entecavir, lamivudine, adefovir, tenofovir disoproxil
Phase phase 4
Sponsor Ruijin Hospital
Start date May 2015
End date August 2016
Trial size 324 participants
Trial identifier NCT02560649, PYRAMID

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Masking open label
Primary purpose treatment
Arm
(Experimental)
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 plus entecavir Pegasys; ETV
Peginterferon alfa-2a 180μg /wk plus Entecavir 0.5mg qd for 48 weeks(Arm A and B)
peginterferon alfa-2a plus lamivudine Pegasys; LAM
Peginterferon alfa-2a 180μg /wk plus Lamivudine 0.1g qd for 48 weeks(Arm A and B)
peginterferon alfa-2a plus adefovir Pegasys;ADV
Peginterferon alfa-2a 180μg /wk plus Adefovir 10mg qd for 48 weeks(Arm A and B)
peginterferon alfa-2a plus tenofovir Pegasys;TDF
Peginterferon alfa-2a 180μg /wk plus Tenofovir 300mg qd for 48 weeks(Arm A and B)
(Active Comparator)
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 plus entecavir Pegasys; ETV
Peginterferon alfa-2a 180μg /wk plus Entecavir 0.5mg qd for 48 weeks(Arm A and B)
peginterferon alfa-2a plus lamivudine Pegasys; LAM
Peginterferon alfa-2a 180μg /wk plus Lamivudine 0.1g qd for 48 weeks(Arm A and B)
peginterferon alfa-2a plus adefovir Pegasys;ADV
Peginterferon alfa-2a 180μg /wk plus Adefovir 10mg qd for 48 weeks(Arm A and B)
peginterferon alfa-2a plus tenofovir Pegasys;TDF
Peginterferon alfa-2a 180μg /wk plus Tenofovir 300mg qd for 48 weeks(Arm A and B)
(Active Comparator)
nucleoside analogue(NUC): HBsAg>200IU/ml at week 24 (Following treatment with Peginterferon alfa-2a plus nucleoside analogue(NUC) for 24 weeks)
entecavir ETV
Entecavir 0.5mg qd for 24 weeks(Arm C)
lamivudine LAM
Lamivudine 0.1g qd for 24 weeks(Arm C)
adefovir Adefovir dipivoxil;ADV
Adefovir 10mg qd for 24 weeks(ArmC)
tenofovir disoproxil Tenofovir disoproxil;TDF
Tenofovir 300mg qd for 24 weeks(Arm C)

Primary Outcomes

Measure
Number of participants who achieve HBsAg clearance
time frame: Week 48

Secondary Outcomes

Measure
Number of participants who achieve HBsAg seroconversion
time frame: Week 48
Number of participants who achieve HBeAg loss
time frame: Week 48
Number of participants who achieve HBeAg seroconversion
time frame: Week 48
Percentage of of participants who achieve HBsAg decline >2log from baseline(0 week)
time frame: Week 48
Percentage of of participants who achieve HBsAg <10IU/mL
time frame: Week 48
Percentage of of participants who achieve combined response(defined as HBeAg seroconversion and HBVDNA<300copies/mL)
time frame: Week 48
Percentage of of participants who achieve dural response I (defined as HBeAg seroconversion and HBsAg<100IU/mL)
time frame: Week 48
Percentage of of participants who achieve dural response II (defined as HBeAg seroconversion and HBsAg<10IU/mL)
time frame: Week 48
Number of participants who relapses (HBVDNA>1000copies/ml)
time frame: Week 48
Number of Participants with AE
time frame: Week 48
Number of Participants with SAE
time frame: Week 48

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

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

Additional Information

Official title A Prospective, Randomized, Multicenter, Open-label, Exploratory Study of Utilizing of "Response-Guided-Therapy (RGT)" Strategy on Optimal Nucleoside Analogue (NUC)-Experienced Patients
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.
Trial information was received from ClinicalTrials.gov and was last updated in September 2015.
Information provided to ClinicalTrials.gov by Ruijin Hospital.