Pegylated Interferon and Ribavirin Therapy in Chronic Hepatitis Genotype 4

Hepatitis C Clinical Trial

Official title:

Role of Rapid Virologic Response in Determining Treatment Duration of Peginterferon Alfa-2b/Ribavirin in Chronic Hepatitis C Genotype 4

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00277862
• Other study ID #: G43230832638
• Status: Completed
• Phase: Phase 4
• First received: January 15, 2006
• Last updated: February 25, 2008
• Start date: April 2002
• Est. completion date: April 2007

Study information

• Verified date: February 2008
• Source: Ain Shams University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Genotype 4 is the least-studied hepatitis C virus genotype and was considered a difficult to treat genotype due to the disappointing response of chronic hepatitis C genotype 4 to conventional interferon monotherapy. Recent reports showed that pegylated interferon and ribavirin combination therapy markedly increased the SVR rate to 55-70%. The duration of treatment has not been accurately defined. The main objective of this is to assess the duration of pegylated interferon ribavirin therapy in chronic hepatitis genotype 4 and assess the clinical utility of rapid and early virologic response in determining the optimal duration of peg interferon ribavirin therapy in chronic hepatitis C.

Description:

Hepatitis C virus (HCV) genotype 4 is the most frequent cause of chronic hepatitis C in Middle East, North Africa and sub-Saharan Africa. In countries like Egypt, 73 to 90% of cases of chronic hepatitis C are caused by genotype 4. Recently, epidemiological reports showed spread of HCV-4 infection in Western countries such as France, Italy, Greece, Spain and the United States particularly among intravenous drug users.

Genotype 4 is the least-studied hepatitis C virus genotype and was considered a difficult to treat genotype due to the disappointing response of chronic hepatitis C genotype 4 to conventional interferon monotherapy. Recent reports showed that pegylated interferon and ribavirin combination therapy markedly increased the SVR rate to 55-70%. We have previously shown that, treatment patients with chronic HVCG4with PEG-IFN α-2b plus ribavirin for 36 or 48 weeks was more effective (SVR 66% and 69%, respectively) than for 24 weeks.

It has been shown in previous studies on chronic hepatitis C genotype 1 that individuals who achieve an early virologic have a higher chance to achieve a sustained virologic response. Peg interferon and ribavirin therapy is associated with adverse events and is expensive; therefore, careful determination of the optimal treatment duration is crucial as it spares the patient unnecessary or prolonged therapy and enhances the cost-effectiveness of therapy.

Therefore the main objective of this randomized, multicenter trial is to assess the clinical utility of rapid and early virologic response in determining the optimal duration of peg interferon ribavirin therapy in chronic hepatitis C.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 280
• Est. completion date: April 2007
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:Adult males and females, 18 to 50 years of age; with documented chronic hepatitis C according to the following criteria: elevated serum alanine aminotransferase (ALT) above the upper limit of normal (40 U/l) on two occasions during the preceding six months; anti-HCV positive anti-body status assessed by second generation enzyme linked immunosorbent assay (Roche Diagnostics, Branchburg, New Jersey, USA); positive polymerase chain reaction for HCV RNA (Cobas Amplicor HCV Monitor v2.0; lower limit of quantitation 50 IU/mL); genotype 4; and criteria for chronic hepatitis C in liver biopsy performed within the preceding year with no signs of cirrhosis or bridging fibrosis on pretreatment liver biopsy.

Exclusion Criteria:

• Previous IFN-alpha therapy; other liver diseases such as hepatitis A, hepatitis B, schistosomiasis, autoimmune hepatitis, alcoholic liver disease, drug induced hepatitis, or decompensated liver disease; coinfection with schistosomiasis or human immunodeficiency virus; neutro¬penia (,1 500/mm3); thrombocytopenia (,90 000/mm3); creatinine concentration .1.5 times the upper limit of normal; serum a fetoprotein concentration .25 ng/ml; organ transplant; neoplastic disease; severe cardiac or pulmonary disease; unstable thyroid dysfunction; psychiatric disorder; current pregnancy or breast feeding; or therapy with immunomodulatory agents within the last six months.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis, Chronic

Intervention

Drug:
• Pegylated IFN- alpha 2b

• Ribavirin

Locations

Country	Name	City	State
Egypt	DIACSERA	Cairo
Egypt	MISR Welding	Cairo
Egypt	AUS Specialized Hospital,	Cairo;	Cairo,
Egypt	ELectricity Auth	Mynia and Cairo

Sponsors (5)

Lead Sponsor	Collaborator
Ain Shams University	Fulbright, International Society for Infectious Diseases, Schering-Plough, TEMPUS

Country where clinical trial is conducted

Egypt, 

References & Publications (2)

Kamal SM, El Tawil AA, Nakano T, He Q, Rasenack J, Hakam SA, Saleh WA, Ismail A, Aziz AA, Madwar MA. Peginterferon {alpha}-2b and ribavirin therapy in chronic hepatitis C genotype 4: impact of treatment duration and viral kinetics on sustained virological response. Gut. 2005 Jun;54(6):858-66. — View Citation

Kamal SM, Fehr J, Roesler B, Peters T, Rasenack JW. Peginterferon alone or with ribavirin enhances HCV-specific CD4 T-helper 1 responses in patients with chronic hepatitis C. Gastroenterology. 2002 Oct;123(4):1070-83. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	sustained virologic response defined as undetectable serum HCV RNA levels (Amplicor HCV, Roche Molecular Systems; lower limit of detection (LLD) of 50 IU/mL)		18 months	Yes
Secondary	Virologic response at the end of treatment (EOT) defined as undetectable HCV RNA serum levels (50 IU/ml) at the end of the scheduled treatment period		6-12 months and 6 months follow-up	Yes
Secondary	sustained virologic response (primary) histological response (secondary) biochemical response (secondary)		6-12 months treatment), 6 months follow-up	Yes