Ignite Creation Date:
2024-05-05 @ 11:44 AM
Last Modification Date:
2024-10-26 @ 9:12 AM
Study NCT ID:
NCT00117533
Status:
UNKNOWN
Last Update Posted:
2006-05-25
First Post:
2005-06-30
Brief Title:
Pegylated Interferon Alfa-2b Plus Ribavirin in Chronic Hepatitis B and Delta
Sponsor:
National Taiwan University Hospital
Organization:
National Taiwan University Hospital
Study Overview
Official Title:
A Pilot Study to Evaluate the Efficacy and Safety of Pegylated Interferon Alfa-2b Plus Ribavirin in the Treatment of Patients With Dual Chronic Hepatitis B and Delta
Status:
UNKNOWN
Status Verified Date:
2005-09
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 treatment of choice for chronic hepatitis D is uncertain The investigators hypothesize that pegylated interferon IFN alfa-2b in combination with ribavirin RBV may be effective in the treatment of chronic hepatitis D patients who are also infected by hepatitis B virus HBV The purpose of this study is to test this hypothesis The investigators will use pegylated IFN alfa-2b in combination with RBV for the treatment of patients with dual chronic hepatitis D virus HDV and HBV infection A 24-week course of combination therapy pegylated IFNRBV will be used
Detailed Description:
Recombinant IFN alfa possesses anti-viral and immunomodulatory effects and has been shown to be effective in chronic hepatitis B Davis et al 1989 Bisceclie et al 1989 Interferon alfa is also one of the approved treatments for chronic hepatitis B Administration of IFN alfa-2b to adults leads to disappearance of HBV DNA with or without HBeAg seroconversion in 30-50 of patients which is two to three times above the rate of yearly spontaneous HBeAg seroconversion 10-15 Normalization of serum ALT occurs in most cases Loss of HBsAg is observed in 10-15 of Caucasian patients during the prolonged post-treatment follow-up period Recently studies suggested that a higher proportion of patients receiving pegylated IFN could achieve HBeAg seroconversion and control of HBV replication Marcellin et al 2004 Lau et al 2004 Jensen et al 2004
RBV is another antiviral nucleotide analogue with few adverse effects Sidwell et al 1972 Patterson et al 1990 RBV alone can modestly inhibit HDV or HBV replication Choi et al 1989 The beneficial effect of combined IFN plus RBV in the treatment of chronic hepatitis B has also been shown in previous studies Cotonat et al 2000 Why RBV can greatly enhance the treatment efficacy is not clear It had been shown that ribavirin could inhibit interleukin-4 an inhibitor of cytotoxic T lymphocyte activity and preserves the interleukin-2 and gamma IFN activities Other studies revealed that the enhanced efficacy was associated with HBV- or other virus-specific type 1 cytokine-mediated T helper cell responses Cramp et al 2000 Tam et al 1999 Hultgren et al 1998 Fang et al 2002 Fang et al 2000 Rico et al 2001 Thus the combination therapy may augment virus-specific cytotoxic T lymphocytes and non-specific immune response and effectively shift the immune responses to the more potent antiviral type 1 T-helper profile Hultgren et al 1998
HDV like HCV is a RNA virus Indeed RBV had also been shown to be active against HDV replication in cell cultures Choi et al 1989 The investigators therefore hypothesize that pegylated IFN alfa-2b in combination with RBV can yield an efficacy in chronic hepatitis D patients who are dually infected by HBV The purpose of this protocol is to test this hypothesis A previous study found that high-dose IFN may improve the efficacy for chronic hepatitis D patients Another pilot study using IFN alfa plus RBV also demonstrated that the seroclearance of HCV RNA was not affected by HBV coinfection Liu et al 2003 The investigators thus use pegylated IFN alfa-2b in combination with RBV for the treatment of patients with dual chronic HDV and HBV infection
The treatment choice for chronic hepatitis D was not clarified till now In this proposal the dosage and duration for the combination regimen are decided mainly by the experience from the treatment of chronic hepatitis B and chronic hepatitis C
The investigators recent study using ribavirin and interferon IFN combination therapy for dual chronic hepatitis B and C suggested that combining ribavirin 1200 mg daily for 6 months together with 6 million units MU IFN-alpha 2a thrice weekly for 12 weeks and then 3 MU for another 12 weeks was effective for the clearance of HCV RNA Liu et al 2003 Twenty-four patients with chronic hepatitis seropositive for both hepatitis B surface antigen and antibody to HCV received ribavirin 1200 mg daily for 6 months together with 6 million units MU IFN-alpha 2a thrice weekly for 12 weeks and then 3 MU for another 12 weeks The serum HCV clearance rate was 43 24 weeks posttreatment The serum ALT normalization rate was 43 24 weeks posttreatment In hepatitis B and C dually infected patients combination IFN with ribavirin can achieve a sustained HCV clearance rate comparable with hepatitis C alone Furthermore a previous study revealed that a 12-week RBV therapy was not effective for patients with chronic hepatitis B Kakumu et al 1993 Therefore a 24-week course of combination therapy pegylated IFNRBV will be used
Increased RBV dosage has been considered a contributory factor to the better efficacy in treating refractory genotype HCV For example recent studies suggested that using RBV 800 mg daily is adequate to treat HCV genotype non-1 while the standard dosage of RBV is required to treat HCV genotype 1 NIH 2002 The investigators thus propose to use RBV 1000-1200 mg daily according to the body weight of the patient
RBV is another antiviral nucleotide analogue with few adverse effects Sidwell et al 1972 Patterson et al 1990 RBV alone can modestly inhibit HDV or HBV replication Choi et al 1989 The beneficial effect of combined IFN plus RBV in the treatment of chronic hepatitis B has also been shown in previous studies Cotonat et al 2000 Why RBV can greatly enhance the treatment efficacy is not clear It had been shown that ribavirin could inhibit interleukin-4 an inhibitor of cytotoxic T lymphocyte activity and preserves the interleukin-2 and gamma IFN activities Other studies revealed that the enhanced efficacy was associated with HBV- or other virus-specific type 1 cytokine-mediated T helper cell responses Cramp et al 2000 Tam et al 1999 Hultgren et al 1998 Fang et al 2002 Fang et al 2000 Rico et al 2001 Thus the combination therapy may augment virus-specific cytotoxic T lymphocytes and non-specific immune response and effectively shift the immune responses to the more potent antiviral type 1 T-helper profile Hultgren et al 1998
HDV like HCV is a RNA virus Indeed RBV had also been shown to be active against HDV replication in cell cultures Choi et al 1989 The investigators therefore hypothesize that pegylated IFN alfa-2b in combination with RBV can yield an efficacy in chronic hepatitis D patients who are dually infected by HBV The purpose of this protocol is to test this hypothesis A previous study found that high-dose IFN may improve the efficacy for chronic hepatitis D patients Another pilot study using IFN alfa plus RBV also demonstrated that the seroclearance of HCV RNA was not affected by HBV coinfection Liu et al 2003 The investigators thus use pegylated IFN alfa-2b in combination with RBV for the treatment of patients with dual chronic HDV and HBV infection
The treatment choice for chronic hepatitis D was not clarified till now In this proposal the dosage and duration for the combination regimen are decided mainly by the experience from the treatment of chronic hepatitis B and chronic hepatitis C
The investigators recent study using ribavirin and interferon IFN combination therapy for dual chronic hepatitis B and C suggested that combining ribavirin 1200 mg daily for 6 months together with 6 million units MU IFN-alpha 2a thrice weekly for 12 weeks and then 3 MU for another 12 weeks was effective for the clearance of HCV RNA Liu et al 2003 Twenty-four patients with chronic hepatitis seropositive for both hepatitis B surface antigen and antibody to HCV received ribavirin 1200 mg daily for 6 months together with 6 million units MU IFN-alpha 2a thrice weekly for 12 weeks and then 3 MU for another 12 weeks The serum HCV clearance rate was 43 24 weeks posttreatment The serum ALT normalization rate was 43 24 weeks posttreatment In hepatitis B and C dually infected patients combination IFN with ribavirin can achieve a sustained HCV clearance rate comparable with hepatitis C alone Furthermore a previous study revealed that a 12-week RBV therapy was not effective for patients with chronic hepatitis B Kakumu et al 1993 Therefore a 24-week course of combination therapy pegylated IFNRBV will be used
Increased RBV dosage has been considered a contributory factor to the better efficacy in treating refractory genotype HCV For example recent studies suggested that using RBV 800 mg daily is adequate to treat HCV genotype non-1 while the standard dosage of RBV is required to treat HCV genotype 1 NIH 2002 The investigators thus propose to use RBV 1000-1200 mg daily according to the body weight of the patient
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