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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
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PegINF plus nucleos(i)de analgoue | Experimental | Peginterferon alfa-2a 180μg /wk plus nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks |
|
| nucleos(t)ide analgoue | Active Comparator | nucleos(t)ide analgoue (NA) 1 piece qd for 48 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Peginterferon alfa-2a | Drug | Peginterferon alfa-2a 180ug/wk s.c for 48 weeks |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants who achieve HBeAg seroconversion | 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of participants who achieve HBeAg loss | 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 |
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Inclusion criteria:
Exclusion Criteria:
Co-infection with active hepatitisA, hepatitisC, hepatitisD and/or human immunodeficiency virus (HIV)
AFP>50ng/ml and/or evidence of hepatocellular carcinoma
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:
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)
Pregnant or breast-feeding Women
ANC<1.5x 10^9/L or PLT<90x 10^9/L
Consuming alcohol in excess of 20g/day for women and 30g/day for men within 6 months prior to enrollment
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
History of immunologically mediated disease, (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, rheumatoid arthritis etc.)
History of esophageal varices bleeding or other evidence of esophageal varices bleeding or other symptoms consistent with decompensated liver disease
History of chronic pulmonary disease associated with functional limitation
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)
Hemodialysis patients or patients with renal insufficiency
History of a severe seizure disorder or current anticonvulsant use
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
History of thyroid disease poorly controlled on prescribed medications
Evidence of severe retinopathy or clinically relevant ophthalmologic disorder
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
Immunomodulatory treatment (including interferon) or LDT within 1 year prior to the first dose of treatment
Patients included in another trial or having been given investigational drugs within 12 weeks prior to screening
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Qing Xie | Contact | 86-13651804273 | xieqingrjh2015@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Qing Xie | Ruijin Hospital | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The Third People's Hospital of Guilin | Recruiting | Guilin | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 14697813 | Result | Lai CL, Ratziu V, Yuen MF, Poynard T. Viral hepatitis B. Lancet. 2003 Dec 20;362(9401):2089-94. doi: 10.1016/S0140-6736(03)15108-2. | |
| 24954675 | Result | Trepo C, Chan HL, Lok A. Hepatitis B virus infection. Lancet. 2014 Dec 6;384(9959):2053-63. doi: 10.1016/S0140-6736(14)60220-8. Epub 2014 Jun 18. |
Not provided
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| ID | Term |
|---|---|
| D019694 | Hepatitis B, Chronic |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| C100416 | peginterferon alfa-2a |
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| nucleos(t)ide analgoue | Drug | nucleos(t)ide analgoue (NA) 1 piece p.o for 48 weeks |
|
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 | 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 | 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 | 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 | 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) | 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) | 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) | 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) | 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 | Number of participants with adverse events as a measure of safety and tolerability | at week 48 |
| Number of Participants with SAE | Number of participants with SAEs as a measure of safety and tolerability | at week 48 |
| Ruijin Hospital | Recruiting | Shanghai | China |
|
| Shanghai Public Health Clinical Center | Recruiting | Shanghai | China |
|
| 10051494 | Result | Tassopoulos NC, Volpes R, Pastore G, Heathcote J, Buti M, Goldin RD, Hawley S, Barber J, Condreay L, Gray DF. Efficacy of lamivudine in patients with hepatitis B e antigen-negative/hepatitis B virus DNA-positive (precore mutant) chronic hepatitis B. Lamivudine Precore Mutant Study Group. Hepatology. 1999 Mar;29(3):889-96. doi: 10.1002/hep.510290321. |
| 12606735 | Result | Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003 Feb 27;348(9):808-16. doi: 10.1056/NEJMoa020681. |
| 20049753 | Result | Chang TT, Lai CL, Kew Yoon S, Lee SS, Coelho HS, Carrilho FJ, Poordad F, Halota W, Horsmans Y, Tsai N, Zhang H, Tenney DJ, Tamez R, Iloeje U. Entecavir treatment for up to 5 years in patients with hepatitis B e antigen-positive chronic hepatitis B. Hepatology. 2010 Feb;51(2):422-30. doi: 10.1002/hep.23327. |
| 25348661 | Result | Brouwer WP, Xie Q, Sonneveld MJ, Zhang N, Zhang Q, Tabak F, Streinu-Cercel A, Wang JY, Idilman R, Reesink HW, Diculescu M, Simon K, Voiculescu M, Akdogan M, Mazur W, Reijnders JG, Verhey E, Hansen BE, Janssen HL; ARES Study Group. Adding pegylated interferon to entecavir for hepatitis B e antigen-positive chronic hepatitis B: A multicenter randomized trial (ARES study). Hepatology. 2015 May;61(5):1512-22. doi: 10.1002/hep.27586. Epub 2015 Feb 27. |
| D018347 |
| Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |