Treatment With Peginterferon Alfa-2a (40 KD) of Chronic Hepatitis B Patients, Who Have Failed Anti-viral Treatment

NCT00226382 | Completed Phase 4

• 1 other identifier: Pegasys Study
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to investigate the HBV DNA suppression (and HBeAg seroconversion among HBeAg positive patients) pegylated interferon treatment at 24 weeks after end of treatment among patients who have failed anti-viral treatment in the past.

Conditions

Chronic Hepatitis B

Keywords

Chronic Hepatitis B; Pegylated Interferon-alfa-2a; Pegasys

Outcome Measures

Primary Outcomes (1)

• HBeAg positive patients response is defined as HBeAg loss and presence of anti-HBe (HBeAg seroconversion), HBeAg Negative patients response is defined as DNA<20,000 copies/ml and ALT normalization both measured at week 72

Secondary Outcomes (2)

• Percentage of patients with HBV DNA levels <100,000 copies/ml at week 72, Percentage of patients with HBV DNA levels <10,000 copies/ml at week 72

• - Percentage of patients with HBV DNA levels negative by PCR at week 72, ALT normalization at week 72, HBsAg seroconversion at week 72, Safety of treatment

Interventions

Pegylated Interferon-alfa-2a DRUG

Pegasys once weekly

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Positive HBsAg for more than 6 months
• Detectable HBV DNA (patients must have \>100,000 copies/ml as measured by PCR)
• HBeAg positive and negative patients are recruited.
• Previous use of nucleoside (nucleotide) analogues for at least 12 months, and the treatment has been stopped for at least 6 months.
• elevated serum ALT \> 1.5x upper limited of normal but \<= 10X as determined by two abnormal values taken \>14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained during the screening period.
• CHB confirmed by liver biopsy in the past or by clinical evaluation.
• Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug. Additionally, all females must be using reliable contraception during the study and for 3 months after treatment completion.

You may not qualify if:

• Evidence of decompensated liver disease (Childs B-C), hepato-cellular carcinoma, pre-existing severe depression or other psychiatric disease, significant cardiac disease, significant renal disease, seizure disorders or severe retinopathy.
• Patients who have received antiviral therapy for their chronic hepatitis B or any systemic anti-viral, anti-neoplastic or immuno-modulatory treatment (including supraphysiologic doses of steroids and radiation) within the past 6 months.
• Positive test at screening for anti-HIV, anti-HCV.
• Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded. Exception: patients who have had a limited (\<=7 days) course of acyclovir for herpetic lesions more than 1 month prior to the first administration of test drug are not excluded.
• Serum total bilirubin \> 3X upper limit of normal at screening.
• History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease.
• History or other evidence of a medical condition associated with chronic liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver diseases including Wilson's and alpha1-antitrypsin deficiency, alcoholic liver disease, toxin exposures, thalassemia).
• Women with ongoing pregnancy or who are breast feeding.
• Neutrophil count \<1500 cells/mm3 at screening.
• Platelet count \<90,000 cells/mm3 at screening.
• Hemoglobin \< 11.5 g/dL for females and \< 12.5 g/dL for men at screening.
• Serum creatinine level \>120 umol/ml for men and \>105 umol/ml for women at screening.
• History of severe psychiatric disease, especially depression.
• History of immunologically mediated disease
• History or other evidence of chronic pulmonary disease associated with functional limitation. Severe cardiac disease

Sponsors & Collaborators

• Chinese University of Hong Kong: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Cheng Suen Man Shook Hepatitis Center, Institute of Digestive Disease, The Chinese University of Hong Kong, Prince of Wales Hospital

Hong Kong SAR, China

Location

Related Publications (8)

• Lai CL, Chien RN, Leung NW, Chang TT, Guan R, Tai DI, Ng KY, Wu PC, Dent JC, Barber J, Stephenson SL, Gray DF. A one-year trial of lamivudine for chronic hepatitis B. Asia Hepatitis Lamivudine Study Group. N Engl J Med. 1998 Jul 9;339(2):61-8. doi: 10.1056/NEJM199807093390201.

  PMID: 9654535 BACKGROUND

• Marcellin P, Chang TT, Lim SG, Tong MJ, Sievert W, Shiffman ML, Jeffers L, Goodman Z, Wulfsohn MS, Xiong S, Fry J, Brosgart CL; Adefovir Dipivoxil 437 Study Group. Adefovir dipivoxil for the treatment of hepatitis B e antigen-positive chronic hepatitis B. N Engl J Med. 2003 Feb 27;348(9):808-16. doi: 10.1056/NEJMoa020681.

  PMID: 12606735 BACKGROUND

• Leung NW, Lai CL, Chang TT, Guan R, Lee CM, Ng KY, Lim SG, Wu PC, Dent JC, Edmundson S, Condreay LD, Chien RN; Asia Hepatitis Lamivudine Study Group. Extended lamivudine treatment in patients with chronic hepatitis B enhances hepatitis B e antigen seroconversion rates: results after 3 years of therapy. Hepatology. 2001 Jun;33(6):1527-32. doi: 10.1053/jhep.2001.25084.

  PMID: 11391543 BACKGROUND

• Cooksley WG, Piratvisuth T, Lee SD, Mahachai V, Chao YC, Tanwandee T, Chutaputti A, Chang WY, Zahm FE, Pluck N. Peginterferon alpha-2a (40 kDa): an advance in the treatment of hepatitis B e antigen-positive chronic hepatitis B. J Viral Hepat. 2003 Jul;10(4):298-305. doi: 10.1046/j.1365-2893.2003.00450.x.

  PMID: 12823597 BACKGROUND

• Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82. doi: 10.1056/NEJMoa020047.

  PMID: 12324553 BACKGROUND

• Zeuzem S, Feinman SV, Rasenack J, Heathcote EJ, Lai MY, Gane E, O'Grady J, Reichen J, Diago M, Lin A, Hoffman J, Brunda MJ. Peginterferon alfa-2a in patients with chronic hepatitis C. N Engl J Med. 2000 Dec 7;343(23):1666-72. doi: 10.1056/NEJM200012073432301.

  PMID: 11106715 BACKGROUND

• Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, Lu ZM, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Button P, Pluck N; Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004 Sep 16;351(12):1206-17. doi: 10.1056/NEJMoa040431.

  PMID: 15371578 BACKGROUND

• Chan HL, Chui AK, Lau WY, Chan FK, Wong ML, Tse CH, Rao AR, Wong J, Sung JJ. Factors associated with viral breakthrough in lamivudine monoprophylaxis of hepatitis B virus recurrence after liver transplantation. J Med Virol. 2002 Oct;68(2):182-7. doi: 10.1002/jmv.10185.

  PMID: 12210406 BACKGROUND

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

peginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Henry LY Chan, MD

  Chinese University of Hong Kong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 23, 2005
• First Posted: September 27, 2005
• Study Start: January 1, 2005
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: June 11, 2010

Record last verified: 2008-10

Locations

CN (1)