Ignite Creation Date:
2024-05-05 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 9:15 AM
Study NCT ID:
NCT00154869
Status:
UNKNOWN
Last Update Posted:
2007-08-13
First Post:
2005-09-08
Brief Title:
Peginterferon Alfa-2a Plus Ribavirin for Chronic Hepatitis CHepatitis B Co-Infection and Chronic Hepatitis C
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
An Open Label Comparative Multi-Center Study to Evaluate the Efficacy and Safety of Peginterferon Alfa-2a Plus Ribavirin in the Treatment of Patients With Chronic Hepatitis CHepatitis B Co-Infection and Chronic Hepatitis C
Status:
UNKNOWN
Status Verified Date:
2005-08
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:
The investigators pilot study indicates that hepatitis C virus HCV- and hepatitis B virus HBV-coinfected patients with predominantly active hepatitis C and those with predominantly active hepatitis B may need different anti-viral regimens Since in the majority of these coinfected patients the hepatitis activity is more likely due to HCV than to HBV the optimal therapeutic regimen for HCV- and HBV-coinfected patients with predominantly active hepatitis C will first be investigated The combination therapy using pegylated interferons IFNs such as PEG-IFN alfa-2a has been shown to have a superior efficacy than that using conventional IFN in the treatment of monoinfected chronic hepatitis C This new combination therapy might also further enhance the treatment efficacy in HCV- and HBV- coinfected patients The investigators therefore propose to initiate a trial comparing the efficacy of pegylated IFN plus ribavirin RBV in dual chronic hepatitis B and C versus that in chronic hepatitis C only for both HCV genotype 1 and 23 patients The efficacy using a 24-week combination therapy in the sustained clearance of serum HCV RNA is equivalent to that using a 48-week combination therapy in patients with HCV genotype non-1 Hadziyannis et al EASL 2002 A 48-week course of pegylated IFN and RBV combination therapy in contrast has been shown to yield a better efficacy in the sustained clearance of serum HCV RNA in patients with HCV genotype 1 than a 24-week combination therapy in western countries Hadziyannis et al EASL 2002 Poynard et al 1998 The primary objective of the current proposal is to investigate and compare the efficacy of combination therapy using pegylated IFN plus RBV on the clearance of serum HCV RNA in both dually infected patients with a dominant HCV infection and HCV monoinfected patients Therefore in this proposal the treatment duration will be 24 weeks for HCV genotype 23 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV and will be 48 weeks for HCV genotype 1 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV
Detailed Description:
Around the world the majority of hepatitis C patients suffer a monoinfected chronic HCV infection Current regimen on this group of patients received much attention and resulted in rapid advances McHutchison et al 1998 However there are certain understudied populations with chronic hepatitis C Strader DB 2002 One important group of them is the patients co-infected by HBV In hepatitis B or C endemic areas the number of subjects with dual infections of both hepatitis C and B is substantial Chen et al 1990 Tsai et al 1994 Liaw 1995 Pramoolsinsap et al 1999 For example in Taiwan anti-HCV was present in 11 of patients with HBV-related chronic liver diseases Chen et al 1990 Liaw 1995 and HBsAg positive rate was 12 in anti-HCV-positive patients Tsai et al 1994 In Italy the prevalence of anti-HCV positivity can be as high as 40 in patients with chronic active hepatitis B in some cities Sagnelli et al 1997 Such co-infected patients are rarely encountered in the developed countries except in intravenous drug users hemophiliacs or those receiving hemodialysis Alarmingly the HCV- and HBV- coinfected patients have been shown to carry a greater risk 155 folds of developing LC or HCC than those with HCV or HBV infection only Liaw 1995 Donato et al 1998 Yang et al 2002 Sun et al 2003 Therefore the HBV and HCV dually infected patients also need active treatments Unfortunately current therapeutic targets and ongoing protocols of clinical trials recruit patients with HCV infection only and invariably exclude those co-infected with HBV Thus it is warranted to address this important issue and an effective treatment for these hepatitis C and B dually infected patients is desperately needed
Sporadic studies showed that IFN alone was not effective in clearing HCV or HBV in patients dually infected with hepatitis B and C Liaw 1995 Liaw et al 1997 Weltman et al 1995 Mazzella et al 1999 Guptan et al 1999 A recent study reported that dose augmentation of IFN to 9 MU thrice weekly for 6 months could clear HCV in 31 of the patients Villa et al 2001 Apparently the efficacy was still not adequate Because combining IFN with RBV has been shown to yield much better results in the treatment of chronic hepatitis C than IFN alone Poynard et al 1995 Davis et al 1998 Reichard et al 1998 McHutchison et al 1998 Lai et al 1996 Liaw et al 1997 Schalm et al 1999 the combination therapy might also be more effective in treating dual hepatitis B and C patients To test this we conducted a pilot study using conventional IFN alfa plus ribavirin to treat 24 patients coinfected with HCV and HBV The 24-week combination regimen with IFN and ribavirin cleared HCV in 43 921 of the patients dually infected with hepatitis B and C The result was comparable to that in patients with monoinfected chronic hepatitis C Normalization of serum ALT was obtained in 38 of the patients 24 weeks after the end of the treatment In addition we found that although the end-of-treatment clearance rate of HCV RNA was comparable between patients infected with genotype 1b and those with genotype 2a or 2b the clearance of HCV RNA sustained much less commonly in those infected by HCV genotype 1b 21 vs 86 P005 Actually two recent studies from southern Taiwan also demonstrated that the efficacy of combination therapy using interferon plus ribavirin on the clearance of serum HCV RNA was comparable between HBV and HCV coinfected patients versus HCV monoinfected patients Wang et al 2003 Yu et al 2003 Based on these findings we suggested that comparable efficacy of combination therapy using interferon plus ribavirin on the clearance of serum HCV RNA can be achieved in patients with HBV and HCV coinfected patients versus HCV monoinfected patients Nevertheless a more effective regimen is still needed for those dually infected patients particularly for those with HCV genotype 1
In our pilot study we treated 24 patients coinfected with HCV and HBV as a single group The majority of these patients had detectable hepatitis C viremia but were anti-HBe positive and with a lower serum HBV titer Therefore hepatitic activity was more likely due to HCV than to HBV Nevertheless a few patients were HBeAg positive and had a higher serum HBV titer 105 copiesmL but with a low or undetectable serum HCV RNA In them the hepatitis was likely due to active hepatitis B Importantly none of the dually infected patients with predominantly active hepatitis B had biochemical and HCV virologic response both at the end of combination therapy and at 24 weeks post-treatment follow-up These two groups of patients may need different anti-viral regimens according to the major offending virus in the liver To treat dual hepatitis C and B patients with dominantly active hepatitis C we may use IFN conventional or pegylated form and RBV and the treatment schedule may be extended to one year to enhance the efficacy for those with HCV genotype 1 However to treat dually infected patients with a dominant HBV infection the treatment strategy may be different
Our pilot study indicates that HCV- and HBV-coinfected patients with predominantly active hepatitis C and those with predominantly active hepatitis B may need different anti-viral regimens Since in the majority of these coinfected patients the hepatitis activity is more likely due to HCV than to HBV the optimal therapeutic regimen for HCV- and HBV-coinfected patients with predominantly active hepatitis C will first be investigated The combination therapy using pegylated IFNs such as PEG-IFN alfa-2a has been shown to have a superior efficacy than that using conventional IFN in the treatment of monoinfected chronic hepatitis C This new combination therapy might also further enhance the treatment efficacy in HCV- and HBV- coinfected patients We therefore propose to initiate a trial comparing the efficacy of pegylated IFN plus RBV in dual chronic hepatitis B and C vs that in chronic hepatitis C only for both HCV genotype 1 and 23 patients The efficacy using a 24-week combination therapy in the sustained clearance of serum HCV RNA is equivalent to that using a 48-week combination therapy in patients with HCV genotype non-1 Hadziyannis et al EASL 2002 A 48-week course of pegylated IFN and RBV combination therapy in contrast has been shown to yield a better efficacy in the sustained clearance of serum HCV RNA in patients with HCV genotype 1 than a 24-week combination therapy in western countries Hadziyannis et al EASL 2002 Poynard et al 1998 The primary objective of the current proposal is to investigate and compare the efficacy of combination therapy using pegylated IFN plus RBV on the clearance of serum HCV RNA in both dually infected patients with a dominant HCV infection and HCV monoinfected patients Therefore in this proposal the treatment duration will be 24 weeks for HCV genotype 23 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV and will be 48 weeks for HCV genotype 1 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV
Sporadic studies showed that IFN alone was not effective in clearing HCV or HBV in patients dually infected with hepatitis B and C Liaw 1995 Liaw et al 1997 Weltman et al 1995 Mazzella et al 1999 Guptan et al 1999 A recent study reported that dose augmentation of IFN to 9 MU thrice weekly for 6 months could clear HCV in 31 of the patients Villa et al 2001 Apparently the efficacy was still not adequate Because combining IFN with RBV has been shown to yield much better results in the treatment of chronic hepatitis C than IFN alone Poynard et al 1995 Davis et al 1998 Reichard et al 1998 McHutchison et al 1998 Lai et al 1996 Liaw et al 1997 Schalm et al 1999 the combination therapy might also be more effective in treating dual hepatitis B and C patients To test this we conducted a pilot study using conventional IFN alfa plus ribavirin to treat 24 patients coinfected with HCV and HBV The 24-week combination regimen with IFN and ribavirin cleared HCV in 43 921 of the patients dually infected with hepatitis B and C The result was comparable to that in patients with monoinfected chronic hepatitis C Normalization of serum ALT was obtained in 38 of the patients 24 weeks after the end of the treatment In addition we found that although the end-of-treatment clearance rate of HCV RNA was comparable between patients infected with genotype 1b and those with genotype 2a or 2b the clearance of HCV RNA sustained much less commonly in those infected by HCV genotype 1b 21 vs 86 P005 Actually two recent studies from southern Taiwan also demonstrated that the efficacy of combination therapy using interferon plus ribavirin on the clearance of serum HCV RNA was comparable between HBV and HCV coinfected patients versus HCV monoinfected patients Wang et al 2003 Yu et al 2003 Based on these findings we suggested that comparable efficacy of combination therapy using interferon plus ribavirin on the clearance of serum HCV RNA can be achieved in patients with HBV and HCV coinfected patients versus HCV monoinfected patients Nevertheless a more effective regimen is still needed for those dually infected patients particularly for those with HCV genotype 1
In our pilot study we treated 24 patients coinfected with HCV and HBV as a single group The majority of these patients had detectable hepatitis C viremia but were anti-HBe positive and with a lower serum HBV titer Therefore hepatitic activity was more likely due to HCV than to HBV Nevertheless a few patients were HBeAg positive and had a higher serum HBV titer 105 copiesmL but with a low or undetectable serum HCV RNA In them the hepatitis was likely due to active hepatitis B Importantly none of the dually infected patients with predominantly active hepatitis B had biochemical and HCV virologic response both at the end of combination therapy and at 24 weeks post-treatment follow-up These two groups of patients may need different anti-viral regimens according to the major offending virus in the liver To treat dual hepatitis C and B patients with dominantly active hepatitis C we may use IFN conventional or pegylated form and RBV and the treatment schedule may be extended to one year to enhance the efficacy for those with HCV genotype 1 However to treat dually infected patients with a dominant HBV infection the treatment strategy may be different
Our pilot study indicates that HCV- and HBV-coinfected patients with predominantly active hepatitis C and those with predominantly active hepatitis B may need different anti-viral regimens Since in the majority of these coinfected patients the hepatitis activity is more likely due to HCV than to HBV the optimal therapeutic regimen for HCV- and HBV-coinfected patients with predominantly active hepatitis C will first be investigated The combination therapy using pegylated IFNs such as PEG-IFN alfa-2a has been shown to have a superior efficacy than that using conventional IFN in the treatment of monoinfected chronic hepatitis C This new combination therapy might also further enhance the treatment efficacy in HCV- and HBV- coinfected patients We therefore propose to initiate a trial comparing the efficacy of pegylated IFN plus RBV in dual chronic hepatitis B and C vs that in chronic hepatitis C only for both HCV genotype 1 and 23 patients The efficacy using a 24-week combination therapy in the sustained clearance of serum HCV RNA is equivalent to that using a 48-week combination therapy in patients with HCV genotype non-1 Hadziyannis et al EASL 2002 A 48-week course of pegylated IFN and RBV combination therapy in contrast has been shown to yield a better efficacy in the sustained clearance of serum HCV RNA in patients with HCV genotype 1 than a 24-week combination therapy in western countries Hadziyannis et al EASL 2002 Poynard et al 1998 The primary objective of the current proposal is to investigate and compare the efficacy of combination therapy using pegylated IFN plus RBV on the clearance of serum HCV RNA in both dually infected patients with a dominant HCV infection and HCV monoinfected patients Therefore in this proposal the treatment duration will be 24 weeks for HCV genotype 23 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV and will be 48 weeks for HCV genotype 1 in patients with dual chronic hepatitis C and B and in patients with monoinfected HCV
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 |
|---|---|---|---|
| ML17862 | None | None | None |