Ignite Creation Date:
2025-12-25 @ 2:54 AM
Ignite Modification Date:
2025-12-26 @ 1:35 AM
Study NCT ID:
NCT00117533
Status:
UNKNOWN
Last Update Posted:
2006-05-25
First Post:
2005-06-30
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Pegylated Interferon Alfa-2b Plus Ribavirin in Chronic Hepatitis B and Delta
Sponsor:
National Taiwan University Hospital
Organization:
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 IFN+RBV 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 1,200 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 1,200 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 IFN+RBV 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 1,200 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 1,200 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 IFN+RBV 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:
Is a FDA Regulated Drug?:
Is a FDA Regulated Device?:
Is an Unapproved Device?:
Is a PPSD?:
Is a US Export?:
Is an FDA AA801 Violation?: