Peg-Intron Versus Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan (Study P04498)(COMPLETED) - Full Text View

Sponsor:	Schering-Plough
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00371761

Purpose

This is an open label, randomized, comparative, multi-center study. Subjects will be screened within 2 weeks prior to study entry to establish eligibility. Subjects who meet all the selection criteria will be randomly assigned 1:1 to (1) once-a-week, subcutaneous Peg-Intron (1.5 mg/kg body weight) or (2) oral adefovir 10 mg daily. The treatment phase will be 24 weeks for Peg-Intron and 48 weeks for adefovir. All subjects completing the assigned treatment phase will be followed up for an additional 48 weeks for Peg-Intron and 24 weeks for adefovir as observation phase. The primary objective is to establish the efficacy profile of Peg-Intron. Secondary objectives are to compare the efficacy profile of Peg-Intron with that of adefovir, compare efficacy of Peg-Intron in lamivudine-naïve and lamivudine-experienced subjects, and to establish the safety profile of Peg-Intron in treating patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B.

Condition	Intervention	Phase
Hepatitis B, Chronic	Drug: Pegylated interferon alfa-2b Drug: Adefovir dipivoxil	Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	An Open-Label, Randomized, Comparative Study With Peg-Intron vs. Adefovir in the Treatment of Chronic Hepatitis B (CHB) e Antigen Positive Patients in Taiwan

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis B

Drug Information available for: Interferon alfa-2a Interferon alfa-2b Adefovir Adefovir dipivoxil Peginterferon Alfa-2b Interferon alfa-n1 Hepatitis B Vaccines Interferons

U.S. FDA Resources

Further study details as provided by Schering-Plough:

Primary Outcome Measures:

Combined response consisting of (a) serological response (loss of HBeAg and appearance of anti-HBe), (b) virological response (HBV DNA <105 copies/mL by real-time PCR), (c) biochemical response (normalization of serum ALT level) [ Time Frame: At Week 72 (for Group A, at 48 weeks post Peg-Intron treatment for up to 24 weeks; for Group B, at 24 weeks post adefovir treatment for up to 48 weeks) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

(a) Combined response; (b) The rates of serologic response,serum HBV DNA <105 copies/mL,HBeAg loss, ALT normalization, HBsAg loss; (c) The rate of histologic response [ Time Frame: (a) At the end of treatment (Group A at 24 weeks, Group B at 48 week); (b) At the end of treatment and at Week 72; (c) At Week 72 ] [ Designated as safety issue: No ]

Estimated Enrollment:	160
Study Start Date:	March 2006
Study Completion Date:	March 2009
Primary Completion Date:	March 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Group A: Experimental Peg-Intron, 1.5 micrograms/kg weekly, for up to 24 weeks followed by a 48-week observation phase	Drug: Pegylated interferon alfa-2b Powder for injection in vials ( 100, and 120 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 24 weeks
Group B: Active Comparator Adefovir, 10 mg daily, for up to 48 weeks followed by a 24-week observation phase	Drug: Adefovir dipivoxil 10 mg adefovir dipivoxil (equivalent to 5.4.5 mg adefovir) tablets, oral, dose of 1 tablet per day for up to 48 weeks

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult male or female, 18 to 70 years of age.
Documented positive serum hepatitis B surface antigen (HBsAg) for a minimum of 6 months prior to randomization.
Hepatitis B virus (HBV) replication and hepatitis documented by:
- Serum HBV DNA >= 105 copies/mL within 3 months prior to entry
- Positive serum hepatitis B e antigen (HBeAg) within 3 months prior to entry
- Documented presence of ALT twice (1 month apart) within 3 months prior to entry (2 to 10 folds above the upper normal level)
- Liver biopsy finding shows evidence of chronic hepatitis without liver cirrhosis, document acceptable if no anti-HBV treatment within 1 year prior to randomization
- Naïve or exposed to lamivudine (3 months treatment-free interval prior to randomization)
- Adequate renal function (creatinine within normal upper limit).
Compensated liver disease with certain minimum hematological and serum biochemical criteria.
Thyroid stimulating hormone (TSH) and free T4 within normal ranges.
Negative antibody to hepatitis C and hepatitis D.
Negative antibody to human immunodeficiency virus.
Negative evidence for hepatocellular carcinoma by alfa-fetoprotein and ultrasound within 1 month prior to randomization.

Exclusion Criteria:

Women who are pregnant or nursing.
Prior treatment for hepatitis with any interferon or adefovir, or other investigational anti-virus agents.
Prior treatment for hepatitis with immunomodulatory drug within 2 years prior to randomization.
Suspected hypersensitivity to interferon or adefovir.
Liver cirrhosis.
History of severe psychiatric disease, especially depression.
Concurrent malignancies (including hepatocellular carcinoma).
Unstable or significant cardiovascular diseases.
Prolonged exposure to known hepatotoxins.
History of thyroid disease poorly controlled on prescribed medication.
Poorly controlled diabetes mellitus.
Have suspected or confirmed significant hepatic disease from an etiology other than HBV.
Severe renal disease or myeloid dysfunction.
History of organ transplantation other than cornea and hair transplant.
Any medical condition requiring chronic systemic administration of steroids.

Contacts and Locations

No Contacts or Locations Provided

More Information

No publications provided

Responsible Party:	Schering-Plough ( Head, Clinical Trials Registry & Results Disclosure Group )
Study ID Numbers:	P04498
Study First Received:	August 31, 2006
Last Updated:	May 13, 2009
ClinicalTrials.gov Identifier:	NCT00371761 History of Changes
Health Authority:	Taiwan: Department of Health

Keywords provided by Schering-Plough:

Hepatitis B virus
Interferon Alfa-2b

Additional relevant MeSH terms:

Anti-Infective Agents
Liver Diseases
Molecular Mechanisms of Pharmacological Action
Hepatitis, Chronic
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Hepatitis, Viral, Human
Hepadnaviridae Infections
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Hepatitis B, Chronic
Therapeutic Uses
Hepatitis B
Growth Inhibitors

Angiogenesis Modulating Agents
Nucleic Acid Synthesis Inhibitors
Interferon-alpha
Growth Substances
Interferons
Enzyme Inhibitors
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Virus Diseases
Hepatitis
Digestive System Diseases
Peginterferon alfa-2b
DNA Virus Infections
Adefovir dipivoxil

ClinicalTrials.gov processed this record on November 27, 2009