Ignite Creation Date:
2024-05-06 @ 1:52 AM
Last Modification Date:
2024-10-26 @ 11:11 AM
Study NCT ID:
NCT01925820
Status:
UNKNOWN
Last Update Posted:
2014-12-04
First Post:
2013-08-16
Brief Title:
Pegasys Plus Entecavir Versus Entecavir Versus Pegasys for Hepatitis B e Antigen-Negative Chronic Hepatitis B
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Pegasys Plus Entecavir Versus Entecavir Versus Pegasys for Hepatitis B e Antigen-Negative Chronic Hepatitis B
Status:
UNKNOWN
Status Verified Date:
2014-12
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Currently there are several antiviral treatments effective for suppression of viral replication but still failed to cure HBV infection in patients with chronic hepatitis B CHB Seven drugs have been worldwide approved for the treatment of CHB at present conventional IFN IFN alfa lamivudine LAM adefovir dipivoxil ADV pegylated IFN Peg-IFN alfa entecavir ETV telbivudine LdT and tenofovir TDF Conventional or Peg-IFN alfa monotherapy has a narrow range of efficacy is associated with several adverse effects and is inconvenient because of frequent injections Oral nucleotside analogues NA are better tolerated but virologic response to NA is frequently not durable and prolonged treatment is associated with the emergence of drug-resistant HBV mutants
Although the best treatment choice for CHB is not clarified yet certain therapeutic concepts could be derived from the experience of treating patients with chronic hepatitis C or human immunodeficiency virus HIV infection A major advancement in treating hepatitis C or HIV infection has been the development of combination therapy Combination therapy has ever been investigated in patients with CHB but again the optimal strategy remains to be identified Entecavir a carbocyclic deoxyguanosine NA is one of the most potent anti-HBV agents ever discovered In addition the 6-year drug resistance rate is 12 in selected lamivudine-naïve cohorts Pegylated interferon alfa-2a possesses both antiviral and immunomodulatory effects Overall satisfactory virologic and serologic responses could be achieved using pegylated IFN alfa in around 30-44 of these patients Whether the combination therapy using Peg-IFN alfa-2a plus ETV can achieve a long-term beneficial effect against ETV or Peg-IFN alfa-2a alone is not clarified A prior single-arm pilot study suggested that similar combination therapy may be beneficial in patients with CHB In this proposal the investigators thus hypothesize that the efficacy by using combination therapy with Peg-IFN alfa-2a plus prolonged ETV is superior to that by using ETV or Peg-IFN alfa-2a alone in that Peg-IFN may restore host immunity against HBV and prolonged ETV can maximize viral suppression
The objective of this clinical trial is to evaluate the efficacy of the combination of Peg-IFN alfa-2a at a dose of 180 mcg administered subcutaneously per week and ETV 05 mg daily for 48 weeks followed by ETV 05 mg daily monotherapy for an additional 96 weeks versus ETV 05 mg daily monotherapy for 144 weeks or Peg-IFN alfa-2a 180 mcg per week for 48 weeks in patients with HBeAg-negative CHB It will be an open-label randomized comparative multi-center clinical trial The recruited patients will be equally randomized into three treatment groups Treatment-free follow-up period will be 48 weeks in both groups of patients The primary parameter is the Simultaneous achievement of HBsAg titer below 100 IUml and HBV DNA below 300 IUml at 144 weeks after start of treatment by an intention-to-treat analysis Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of years 1 2 and 3
The investigators anticipate that the rate of HBsAg 100 IUmL plus HBV DNA 300 IUmL at 3 years of the study period will be 30 for patients receiving Peg-IFN therapy and increased to be 45 for patients receiving Peg-IFN plus entecavir therapy With a 5 nominal significance level two-sided 163 patients per group under a 111 ratio will provide 80 power to detect a difference of 15 in treatment response rates between group I and III Because this will be a 4-year study for each patient the investigators thus anticipate that the dropout rate may be as high as 10 Accordingly a total of 540 180x3 patients will be recruited in order to account for a dropout rate of up to10
Although the best treatment choice for CHB is not clarified yet certain therapeutic concepts could be derived from the experience of treating patients with chronic hepatitis C or human immunodeficiency virus HIV infection A major advancement in treating hepatitis C or HIV infection has been the development of combination therapy Combination therapy has ever been investigated in patients with CHB but again the optimal strategy remains to be identified Entecavir a carbocyclic deoxyguanosine NA is one of the most potent anti-HBV agents ever discovered In addition the 6-year drug resistance rate is 12 in selected lamivudine-naïve cohorts Pegylated interferon alfa-2a possesses both antiviral and immunomodulatory effects Overall satisfactory virologic and serologic responses could be achieved using pegylated IFN alfa in around 30-44 of these patients Whether the combination therapy using Peg-IFN alfa-2a plus ETV can achieve a long-term beneficial effect against ETV or Peg-IFN alfa-2a alone is not clarified A prior single-arm pilot study suggested that similar combination therapy may be beneficial in patients with CHB In this proposal the investigators thus hypothesize that the efficacy by using combination therapy with Peg-IFN alfa-2a plus prolonged ETV is superior to that by using ETV or Peg-IFN alfa-2a alone in that Peg-IFN may restore host immunity against HBV and prolonged ETV can maximize viral suppression
The objective of this clinical trial is to evaluate the efficacy of the combination of Peg-IFN alfa-2a at a dose of 180 mcg administered subcutaneously per week and ETV 05 mg daily for 48 weeks followed by ETV 05 mg daily monotherapy for an additional 96 weeks versus ETV 05 mg daily monotherapy for 144 weeks or Peg-IFN alfa-2a 180 mcg per week for 48 weeks in patients with HBeAg-negative CHB It will be an open-label randomized comparative multi-center clinical trial The recruited patients will be equally randomized into three treatment groups Treatment-free follow-up period will be 48 weeks in both groups of patients The primary parameter is the Simultaneous achievement of HBsAg titer below 100 IUml and HBV DNA below 300 IUml at 144 weeks after start of treatment by an intention-to-treat analysis Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of years 1 2 and 3
The investigators anticipate that the rate of HBsAg 100 IUmL plus HBV DNA 300 IUmL at 3 years of the study period will be 30 for patients receiving Peg-IFN therapy and increased to be 45 for patients receiving Peg-IFN plus entecavir therapy With a 5 nominal significance level two-sided 163 patients per group under a 111 ratio will provide 80 power to detect a difference of 15 in treatment response rates between group I and III Because this will be a 4-year study for each patient the investigators thus anticipate that the dropout rate may be as high as 10 Accordingly a total of 540 180x3 patients will be recruited in order to account for a dropout rate of up to10
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None