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A Study of Combination or Sequential Treatment With PEGASYS (Peginterferon Alfa-2a) and Entecavir in Patients With HBeAg Positive Chronic Hepatitis B

Phase 4
Completed
Conditions
Hepatitis B, Chronic
Interventions
Drug: peginterferon alfa-2a [Pegasys]
Registration Number
NCT00940485
Lead Sponsor
Hoffmann-La Roche
Brief Summary

This 2 arm study will assess the efficacy and safety of Pegasys in combination or sequential treatment with entecavir in patients with HBeAg positive chronic hepatitis B. Patients who have been pretreated with, and responded to, entecavir for 9 to 36 months were randomized to one of 2 groups, to receive Pegasys 180micrograms/week sc for 48 weeks + entecavir 0.5mg po daily for 8 weeks, or entecavir 0.5mg po daily for 48 weeks. The anticipated time on study treatment is 3-12 months.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
200
Inclusion Criteria
  • Adult patients, >=18 and </= 65 years of age
  • HBeAg positive chronic hepatitis B
  • Pre-treatment with entecavir for 9-36 months
Exclusion Criteria
  • Antiviral, antineoplastic or immunomodulatory treatment
  • Co-infection with active hepatitis A, C or D, or HIV
  • Evidence of decompensated liver disease
  • History or other evidence of a medical condition associated with chronic liver disease other than viral hepatitis

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Peginterferon alfa-2a + entecavirpeginterferon alfa-2a [Pegasys]Participants received PEGASYS® (peginterferon alfa-2a)180 micrograms (mcg) subcutaneously once weekly for 48 weeks, plus entecavir 0.5 milligram (mg) orally once daily for 8 weeks.
EntecavirentecavirParticipants received entecavir 0.5 mg orally once daily for 48 weeks.
Peginterferon alfa-2a + entecavirentecavirParticipants received PEGASYS® (peginterferon alfa-2a)180 micrograms (mcg) subcutaneously once weekly for 48 weeks, plus entecavir 0.5 milligram (mg) orally once daily for 8 weeks.
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Hepatitis B Envelope Antigen Seroconversion at Week 48At Week 48

Hepatitis B envelope Antigen (HBeAg) seroconversion was defined as the absence of HBeAg and the presence of antibody to Hepatitis B envelope antigen (anti-HBe).

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With Hepatitis B Surface Antigen Loss at Week 48At Week 48

Loss of Hepatitis B Surface Antigen (HBsAg) was defined as change of detectable HBsAg from positive to negative.

Percentage of Participants With Hepatitis B Virus - Deoxyribonucleic Acid <1000 Copies/ Millilitre at Week 48At Week 48

Blood was collected for Hepatitis B Virus - Deoxyribonucleic Acid (HBV -DNA) and was analysed at the central laboratories using the Roche approved polymerase chain reaction (PCR) methodology at Week 48. Percentage of participants with HBV-DNA \< 1000 copies/mL was reported.

Percentage of Participants With Hepatitis B Surface Antigen Seroconversion at Week 48At Week 48

Hepatitis B Surface Antigen (HBsAg) seroconversion was defined as loss of HBsAg and presence of anti-HBs .(antibody to Hepatitis B surface antigen)

Percentage of Participants With Normalized Alanine Aminotransferase at Week 48At Week 48

Normalized Alanine Aminotransferase (ALT) is defined as having a baseline ALT value \> upper limit of normal (ULN), and a decrease in ALT value to ≤ ULN at the given time point.

Percentage of Participants With Loss of Hepatitis B Envelope Antigen at Week 48At Week 48

Loss of Hepatitis B Envelope Antigen (HBeAg) is defined as the absence of HBeAg.

Number of Participants With Laboratory Abnormalities Which Were Captured as an Adverse EventUp to Week 48

Participants with clinically significant laboratory abnormalities which were captured as an AE (at the \>=5% threshold) were presented.

Quantitative Change in Mean Hepatitis B Envelope Antigen Over TimeUp to Week 48

Quantitative hepatitis B envelope antigen (HBeAg) results were analyzed in central lab. Values that were less than lower limit of quantification (LLOQ) had been replaced by LLOQ when analyzed, e.g. \<1000 was replaced by 1000 and \<0.2 was replaced by 0.2. Quantitative HBeAg value unit was calculated using 'Paul Ehrlich Institute units per millilitre' (PEIU/ml). Change in HBeAg was analysed at Weeks 0, 8, 12, 24, 36, and 48.

Quantitative Change in Mean Hepatitis B Surface Antigen Change Over TimeUp to Week 48

Quantitative Hepatitis B Surface Antigen (HBsAg) results were analyzed in central lab. Values that were less than LLOQ had been replaced by LLOQ when analyzed, e.g. \<1000 was replaced by 1000 and \<0.2 was replaced by 0.2. Quantitative HBsAg calculated using 'International Units Per Millilitre' (IU/mL). Change in HBsAg was analysed at Weeks 0, 8, 12, 24, 36, and 48.

Number of Participants With Incidence of Adverse Events and Serious Adverse EventsUp to Week 48

An adverse event (AE) was defined as any untoward medical occurrence that occurred during the course of the trial after study treatment had started. An adverse event was therefore any unfavourable and unintended sign, symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A Serious Adverse Events (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

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