Ignite Creation Date:
2024-05-05 @ 7:01 PM
Last Modification Date:
2024-10-26 @ 9:42 AM
Study NCT ID:
NCT00597259
Status:
UNKNOWN
Last Update Posted:
2010-06-29
First Post:
2008-01-09
Brief Title:
Pegasys Plus Entecavir Versus Entecavir Alone for Hepatitis Be Antigen-Positive Chronic Hepatitis B
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
Pegasys Plus Entecavir Versus Entecavir Alone for Hepatitis Be Antigen-Positive Chronic Hepatitis B
Status:
UNKNOWN
Status Verified Date:
2010-06
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:
Although the best treatment choice for chronic hepatitis B 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 Whether the combination therapy using Peg-IFN alfa-2a plus ETV can achieve a long-term beneficial effect against ETV alone is not clarified A prior single-arm pilot study suggested that similar combination therapy may be beneficial in patients with chronic hepatitis B In this proposal we thus hypothesize that the efficacy by using combination therapy with pegylated IFN alfa-2a plus ETV is superior to that by using ETV 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 24 weeks followed by ETV 05 mg daily monotherapy for an additional 120 weeks versus ETV 05 mg daily monotherapy for 144 weeks in patients with HBeAg-positive chronic hepatitis B It will be an open-label randomized comparative multi-center clinical trial The recruited patients will be equally randomized into two treatment groups Treatment-free follow-up period will be 48 weeks in both groups of patients All subjects will be assessed for loss of HBeAg presence of anti-HBe loss of HBsAg presence of anti-HBs suppression of HBV DNA and normalization of serum ALT at the end of treatment and end of follow-up Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of years 1 2 and 3 The primary efficacy will be HBeAg seroconversion
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 24 weeks followed by ETV 05 mg daily monotherapy for an additional 120 weeks versus ETV 05 mg daily monotherapy for 144 weeks in patients with HBeAg-positive chronic hepatitis B It will be an open-label randomized comparative multi-center clinical trial The recruited patients will be equally randomized into two treatment groups Treatment-free follow-up period will be 48 weeks in both groups of patients All subjects will be assessed for loss of HBeAg presence of anti-HBe loss of HBsAg presence of anti-HBs suppression of HBV DNA and normalization of serum ALT at the end of treatment and end of follow-up Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of years 1 2 and 3 The primary efficacy will be HBeAg seroconversion
Detailed Description:
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 The short-term treatment goals are thus to control hepatitis activity to obtain hepatitis B e antigen HBeAg seroconversion and to improve necroinflammatory activity and fibrosis of the liver Six drugs have been worldwide approved for the treatment of chronic hepatitis B at present conventional IFN IFN alfa lamivudine LAM adefovir dipivoxil ADV pegylated IFN Peg-IFN alfa entecavir ETV and recently telbivudine LdT Conventional IFN alfa monotherapy has a narrow range of efficacy is associated with several adverse effects and is inconvenient because of frequent injections Lamivudine is better tolerated but virologic response to lamivudine is frequently not durable and prolonged lamivudine treatment is commonly associated with the emergence of drug-resistant HBV mutants Adefovir dipivoxil is effective and has been approved for the treatment of chronic hepatitis B in many countries but is nephrotoxic at doses higher than 10 mg per day for long time Pegylated IFN alfa has been shown to be superior to conventional IFN alfa and lamivudine and has already been approved for the treatment of chronic hepatitis B Overall satisfactory virologic and serologic responses could be achieved using pegylated IFN alfa alone in around 30-44 of these patients Entecavir a carbocyclic deoxyguanosine analog which is active against both lamivudine- and adefovir dipivoxil-naïve and -resistant HBV is the most potent anti-HBV agent ever discovered In addition the 4-year drug resistance rate is 10 in selected lamivudine-naïve patients LdT is another thymidine nucleoside analogue with potent in vitro activity against HBV and approved for CHB Recent phase III GLOBE trials have proved this agent to be more effective in the treatment of HBeAgve and -ve chronic hepatitis B than lamivudine However resistance to telbivudine was noted in around 10 of subjects after 104-week continuous therapy although still fewer than that in patients receiving lamivudine
Although the best treatment choice for chronic hepatitis B 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 Whether the combination therapy using Peg-IFN alfa-2a plus ETV can achieve a long-term beneficial effect against ETV alone is not clarified A prior single-arm pilot study suggested that similar combination therapy may be beneficial in patients with chronic hepatitis B In this proposal we thus hypothesize that the efficacy by using combination therapy with pegylated IFN alfa-2a plus ETV is superior to that by using ETV 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 24 weeks followed by ETV 05 mg daily monotherapy for an additional 120 weeks versus ETV 05 mg daily monotherapy for 144 weeks in patients with HBeAg-positive chronic hepatitis B It will be an open-label randomized comparative multi-center clinical trial The recruited patients will be equally randomized into two treatment groups Treatment-free follow-up period will be 48 weeks in both groups of patients All subjects will be assessed for loss of HBeAg presence of anti-HBe loss of HBsAg presence of anti-HBs suppression of HBV DNA and normalization of serum ALT at the end of treatment and end of follow-up Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of years 1 2 and 3
We anticipate the rate of HBeAg seroconversion primary efficacy parameter to be around 35 at the end of 3-year entecavir therapy but decreases to be 30 at the end of 24-week post-treatment follow-up We also anticipate that by combining Pegasys the rate of seroconversion at the end of treatment is 50 and at the end of 24-week post-treatment follow-up could be 45 With a 5 nominal significance level one-sided 128 patients per group under a 11 ratio a total of 256 patients will provide 80 power to detect a difference of 15 in treatment response rates between group I and II Because this will be a 4-year study for each patient we thus anticipate that the dropout rate may be as high as 15 Accordingly a total of 294 patients will be recruited in order to account for a dropout rate of up to 15
A final analysis will be conducted when all patients have completed 144-week treatment and 48 weeks of follow-up Primary and secondary efficacy parameters will be evaluated by an intention-to-treat analysis Exact 1-sided 95-confidence interval from the binomial distribution will be provided for response rates in individual patient groups All categorical and continuous variables will be analyzed by chi-square test and Student t test respectively For continuous variables with outliers nonparametric test will be used instead The analysis of histologic response will include only those who receive the pre- and post-treatment biopsy
Although the best treatment choice for chronic hepatitis B 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 Whether the combination therapy using Peg-IFN alfa-2a plus ETV can achieve a long-term beneficial effect against ETV alone is not clarified A prior single-arm pilot study suggested that similar combination therapy may be beneficial in patients with chronic hepatitis B In this proposal we thus hypothesize that the efficacy by using combination therapy with pegylated IFN alfa-2a plus ETV is superior to that by using ETV 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 24 weeks followed by ETV 05 mg daily monotherapy for an additional 120 weeks versus ETV 05 mg daily monotherapy for 144 weeks in patients with HBeAg-positive chronic hepatitis B It will be an open-label randomized comparative multi-center clinical trial The recruited patients will be equally randomized into two treatment groups Treatment-free follow-up period will be 48 weeks in both groups of patients All subjects will be assessed for loss of HBeAg presence of anti-HBe loss of HBsAg presence of anti-HBs suppression of HBV DNA and normalization of serum ALT at the end of treatment and end of follow-up Genotypic and virologic resistance to ETV will also be assessed at baseline and at end of years 1 2 and 3
We anticipate the rate of HBeAg seroconversion primary efficacy parameter to be around 35 at the end of 3-year entecavir therapy but decreases to be 30 at the end of 24-week post-treatment follow-up We also anticipate that by combining Pegasys the rate of seroconversion at the end of treatment is 50 and at the end of 24-week post-treatment follow-up could be 45 With a 5 nominal significance level one-sided 128 patients per group under a 11 ratio a total of 256 patients will provide 80 power to detect a difference of 15 in treatment response rates between group I and II Because this will be a 4-year study for each patient we thus anticipate that the dropout rate may be as high as 15 Accordingly a total of 294 patients will be recruited in order to account for a dropout rate of up to 15
A final analysis will be conducted when all patients have completed 144-week treatment and 48 weeks of follow-up Primary and secondary efficacy parameters will be evaluated by an intention-to-treat analysis Exact 1-sided 95-confidence interval from the binomial distribution will be provided for response rates in individual patient groups All categorical and continuous variables will be analyzed by chi-square test and Student t test respectively For continuous variables with outliers nonparametric test will be used instead The analysis of histologic response will include only those who receive the pre- and post-treatment biopsy
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
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| No other ID | None | None | None |