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

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ClinicalTrials.gov Identifier: NCT00226382
Recruitment Status : Completed
First Posted : September 27, 2005
Last Update Posted : June 11, 2010
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
Chinese University of Hong Kong

Tracking Information
First Submitted Date  ICMJE September 23, 2005
First Posted Date  ICMJE September 27, 2005
Last Update Posted Date June 11, 2010
Study Start Date  ICMJE January 2005
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 13, 2006)
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
Original Primary Outcome Measures  ICMJE
 (submitted: September 23, 2005)
  • - 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
Change History Complete list of historical versions of study NCT00226382 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: July 13, 2006)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: September 23, 2005)
  • - 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
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Treatment With Peginterferon Alfa-2a (40 KD) of Chronic Hepatitis B Patients, Who Have Failed Anti-viral Treatment
Official Title  ICMJE Treatment With Peginterferon Alfa-2a (40 KD) (PEGASYS®) of Chronic Hepatitis B Patients, Who Have Failed Anti-viral Treatment. A Pilot Study.
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.
Detailed Description

Chronic hepatitis B is the commonest cause of liver cirrhosis and hepatocellular carcinoma in Hong Kong. Persistent high viraemia and necro-inflammation is associated with higher risk of liver-related complications.

Lamivudine and adefovir dipivoxil are the two anti-viral agents that can suppress the replication of the virus. However, these drugs using either alone or in combination only induce HBeAg seroconversion in less than 20% of patients. Most patients therefore required long-term treatment, which has a risk of development of drug resistance. Premature cessation of these anti-viral agents is usually accompanied by relapse of viraemia and hepatitis.

Pegylated interferon-alfa-2a is modified form of interferon with a 40 kDa polyethylene glycol strand attached to a recombinant interferon. This formulation increases the product's half-life from 7-10 hours to 77 hours. Therefore it can be administered on a more convenient once weekly basis. Pegylated interferon-alfa-2a monotherapy for 24 weeks has been shown to induce sustained HBeAg seroconversion in 35% of patients at the optimal dose of 180 mcg weekly. This drug has been found to be more effective than conventional interferon-alfa in the treatment of chronic hepatitis B as well as chronic hepatitis C.

Data on interferon-based treatment among chronic hepatitis B patients who have failed previous anti-viral treatment is scanty. It is uncertain whether pegylated interferon-alfa-2a treatment will be effective in this group of patients. This is a single-center, pilot study on the virological response of chronic HBV infection to pegylated interferon-alfa-2a among patients who have failed anti-viral treatment in the past. This study will investigate the HBV DNA suppression (and HBeAg seroconversion among HBeAg positive patients) pegylated interferon treatment at 24 weeks after end of treatment.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic Hepatitis B
Intervention  ICMJE Drug: Pegylated Interferon-alfa-2a
Pegasys once weekly
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 10, 2010)
50
Original Enrollment  ICMJE
 (submitted: September 23, 2005)
49
Actual Study Completion Date  ICMJE April 2008
Actual Primary Completion Date April 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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
  • History of a severe seizure disorder or current anticonvulsant use.
  • Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is > 20% within 2 years. Patients with a lesion suspicious of hepatic malignancy on a screening imaging study will only be eligible if the likelihood of carcinoma is 10% following an appropriate evaluation.
  • History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory treatment
  • Major organ transplantation.
  • Thyroid disease with thyroid function poorly controlled on prescribed medications. Patients with abnormal thyroid stimulating hormone or T4 concentrations, with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.
  • History or other evidence of severe retinopathy or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension
  • Inability or unwillingness to provide informed consent or abide by the requirements of the study.
  • History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study.
  • Patients with a value of alpha-fetoprotein >100 ng/mL are excluded, unless stability (less than 10% increase) has been documented over at least the previous 3 months.
  • Evidence of drug and/or alcohol abuse (20g/day for women and 30g/day for men).
  • Patients included in another trial or having been given investigational drugs within 12 weeks prior to screening
  • Any known history of hypersensitivity to interferon.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00226382
Other Study ID Numbers  ICMJE Pegasys Study
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Professor LY Chan, The Chinese University of Hong Kong
Study Sponsor  ICMJE Chinese University of Hong Kong
Collaborators  ICMJE Hoffmann-La Roche
Investigators  ICMJE
Principal Investigator: Henry LY Chan, MD Chinese University of Hong Kong
PRS Account Chinese University of Hong Kong
Verification Date October 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP