search
Back to results

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

Primary Purpose

Hepatitis B, Chronic

Status
Completed
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
entecavir
entecavir
peginterferon alfa-2a [Pegasys]
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Peginterferon alfa-2a + entecavir

Entecavir

Arm Description

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.

Participants received entecavir 0.5 mg orally once daily for 48 weeks.

Outcomes

Primary Outcome Measures

Percentage of Participants With Hepatitis B Envelope Antigen Seroconversion at 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

Percentage of Participants With Loss of Hepatitis B Envelope Antigen at Week 48
Loss of Hepatitis B Envelope Antigen (HBeAg) is defined as the absence of HBeAg.
Percentage of Participants With Hepatitis B Virus - Deoxyribonucleic Acid <1000 Copies/ Millilitre at 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 Loss at 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 Surface Antigen Seroconversion at 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 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.
Quantitative Change in Mean Hepatitis B Envelope Antigen Over Time
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 Time
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 Events
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.
Number of Participants With Laboratory Abnormalities Which Were Captured as an Adverse Event
Participants with clinically significant laboratory abnormalities which were captured as an AE (at the >=5% threshold) were presented.

Full Information

First Posted
June 16, 2009
Last Updated
February 26, 2016
Sponsor
Hoffmann-La Roche
search

1. Study Identification

Unique Protocol Identification Number
NCT00940485
Brief Title
A Study of Combination or Sequential Treatment With PEGASYS (Peginterferon Alfa-2a) and Entecavir in Patients With HBeAg Positive Chronic Hepatitis B
Official Title
A Study on Optimizing HBeAg Seroconversion in HBeAg Positive CHB Patients With Combination or Sequential Treatment of Pegylated Interferon Alpha-2a and Entecavir
Study Type
Interventional

2. Study Status

Record Verification Date
February 2016
Overall Recruitment Status
Completed
Study Start Date
April 2009 (undefined)
Primary Completion Date
December 2011 (Actual)
Study Completion Date
December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
200 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Peginterferon alfa-2a + entecavir
Arm Type
Experimental
Arm Description
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.
Arm Title
Entecavir
Arm Type
Active Comparator
Arm Description
Participants received entecavir 0.5 mg orally once daily for 48 weeks.
Intervention Type
Drug
Intervention Name(s)
entecavir
Intervention Description
0.5mg po daily for 8 weeks
Intervention Type
Drug
Intervention Name(s)
entecavir
Intervention Description
0.5mg po daily for 48 weeks
Intervention Type
Drug
Intervention Name(s)
peginterferon alfa-2a [Pegasys]
Intervention Description
180 micrograms sc/week for 48 weeks
Primary Outcome Measure Information:
Title
Percentage of Participants With Hepatitis B Envelope Antigen Seroconversion at Week 48
Description
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).
Time Frame
At Week 48
Secondary Outcome Measure Information:
Title
Percentage of Participants With Loss of Hepatitis B Envelope Antigen at Week 48
Description
Loss of Hepatitis B Envelope Antigen (HBeAg) is defined as the absence of HBeAg.
Time Frame
At Week 48
Title
Percentage of Participants With Hepatitis B Virus - Deoxyribonucleic Acid <1000 Copies/ Millilitre at Week 48
Description
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.
Time Frame
At Week 48
Title
Percentage of Participants With Hepatitis B Surface Antigen Loss at Week 48
Description
Loss of Hepatitis B Surface Antigen (HBsAg) was defined as change of detectable HBsAg from positive to negative.
Time Frame
At Week 48
Title
Percentage of Participants With Hepatitis B Surface Antigen Seroconversion at Week 48
Description
Hepatitis B Surface Antigen (HBsAg) seroconversion was defined as loss of HBsAg and presence of anti-HBs .(antibody to Hepatitis B surface antigen)
Time Frame
At Week 48
Title
Percentage of Participants With Normalized Alanine Aminotransferase at Week 48
Description
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.
Time Frame
At Week 48
Title
Quantitative Change in Mean Hepatitis B Envelope Antigen Over Time
Description
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.
Time Frame
Up to Week 48
Title
Quantitative Change in Mean Hepatitis B Surface Antigen Change Over Time
Description
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.
Time Frame
Up to Week 48
Title
Number of Participants With Incidence of Adverse Events and Serious Adverse Events
Description
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.
Time Frame
Up to Week 48
Title
Number of Participants With Laboratory Abnormalities Which Were Captured as an Adverse Event
Description
Participants with clinically significant laboratory abnormalities which were captured as an AE (at the >=5% threshold) were presented.
Time Frame
Up to Week 48

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
City
Changsha
ZIP/Postal Code
410008
Country
China
City
Chengdu
ZIP/Postal Code
610041
Country
China
City
Fu Zhou
ZIP/Postal Code
350005
Country
China
City
Guangzhou
ZIP/Postal Code
510515
Country
China
City
Hangzhou
ZIP/Postal Code
310003
Country
China
City
Wuhan
ZIP/Postal Code
430030
Country
China
City
Xi'an
ZIP/Postal Code
710038
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
25814467
Citation
Yan W, Wu D, Wang X, Chen T, Lai Q, Zheng Q, Jiang J, Hou J, Han M, Ning Q. Upregulation of NKG2C+ natural killer cells, TLR-2 expression on monocytes and downregulation of regulatory T-cells influence PEG-IFN treatment efficacy in entecavir-suppressed patients with CHB. Antivir Ther. 2015;20(6):591-602. doi: 10.3851/IMP2953. Epub 2015 Mar 27.
Results Reference
derived
PubMed Identifier
24915612
Citation
Ning Q, Han M, Sun Y, Jiang J, Tan D, Hou J, Tang H, Sheng J, Zhao M. Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial). J Hepatol. 2014 Oct;61(4):777-84. doi: 10.1016/j.jhep.2014.05.044. Epub 2014 Jun 7.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs