PegIntron Treatment of Chronic Hepatitis B e Antigen-Positive Patients (P05170/MK-4031-327)
Primary Purpose
Hepatitis B, Chronic
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
pegylated interferon alpha-2b
pegylated interferon alpha-2b
pegylated interferon alpha-2b
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis B, Chronic
Eligibility Criteria
Inclusion Criteria:
Adults with chronic hepatitis B:
- Serum hepatitis B surface antigen positive for at least 6 months
- Serum hepatitis B e antigen positive
- Serum negative for hepatitis B surface and e antibodies
- Plasma hepatitis B virus deoxyribonucleic acid (DNA) level greater than 20,000 IU/mL
- Alanine aminotransferase (ALT) 2- to 10-times the upper limit of normal
- Compensated liver disease with certain minimum hematological and serum biochemical criteria
Exclusion Criteria:
- Significant hepatic disease from an etiology other than hepatitis B virus
- Antiviral treatment for hepatitis within previous 6 months
- History of severe psychiatric disease, especially depression
- Unstable or significant cardiovascular disease
- Prolonged exposure to known hepatotoxins such as alcohol or drugs
- Any condition that could interfere with the subject participating in and completing the study
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Active Comparator
Experimental
Experimental
Arm Label
PEG 1.0 mcg/kg weekly (QW) * 24 weeks
PEG 1.5 mcg/kg QW * 24 wks
PEG 1.5 mcg/kg QW * 48 wks
Arm Description
PegIntron 1.0 mcg/kg weekly (QW) * 24 weeks + 24 weeks follow-up
PegIntron 1.5 mcg/kg QW * 24 wks + 24 wks follow-up
PegIntron 1.5 mcg/kg QW * 48 wks + 24 wks follow-up
Outcomes
Primary Outcome Measures
Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss
HBeAg Loss was tested by Abbott Microparticle Enzyme Immunoassay (MEIA)
Secondary Outcome Measures
Number of Participants With HBeAg Loss
HBeAg Loss was tested by assay of Abbott MEIA
HBe Seroconversion
HBe seroconversion was defined as HBeAg Loss and Anti-HBeAg Positive. These were tested by assay of Abbott MEIA.
Number of Participants With Hepatitis B Virus - Deoxyriboncleic Acid (HBV-DNA) <20,000 IU/mL
HBV-DNA was tested by assay of Roche Cobas Taqman (the test
lowest limit is 6 IU/mL)
Number of Participants With HBV-DNA < 200 IU/mL
HBV-DNA was tested by assay of Roche Cobas Taqman (the test lowest limit is 6 IU/mL)
Number of Participants With HBV-DNA Undetectable
Undetectable HBV-DNA was defined as having a level <6 IU/mL by polymerase chain reaction (PCR).
Number of Participants With Biochemical Response
Biochemical response was defined as alanine aminotransferase (ALT) normalization.
Number of Participants With Combined Response
Combined response was defined as HBV DNA <20,000 IU/mL and HBe seroconversion and alanine aminotransferase (ALT) normalization
Hepatitis B Surface Antigen (HBsAg) Loss
HBsAg Loss was tested by assay of Abbott MEIA
Hepatitis B Surface Antigen (HBs) Seroconversion
HBs seroconversion was defined as having HBsAg Loss and Anti-HBs Positive
Change From Baseline in Liver Biopsy Score
Method for biopsy scoring was Knodell Scoring System (Histology Activity Index-HAI Score System):
Score I (periportal +/- bridging necrosis): 0 (none) to 10 (multilobular necrosis).
Score II (Intralobular degeneration and focal necrosis): 0 (none) to 4 (Marked [involvement of >2/3 of lobules or nodules]).
Score III (portal inflammation): 0 (none) to 4 (Marked [dense packing of
inflammatory cells in >2/3 of portal tracts]).
Score IV (fibrosis): 0 (none) to 4 (cirrhosis).
Full Information
NCT ID
NCT00536263
First Posted
September 26, 2007
Last Updated
March 9, 2017
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT00536263
Brief Title
PegIntron Treatment of Chronic Hepatitis B e Antigen-Positive Patients (P05170/MK-4031-327)
Official Title
An Open-label, Randomized Study of PegIntron in the Treatment of HBeAg Positive Chronic Hepatitis B Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
September 2007 (undefined)
Primary Completion Date
November 2009 (Actual)
Study Completion Date
November 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine the efficacy and safety of two dosages of PegIntron for treating hepatitis B e antigen (HBeAg) positive chronic hepatitis B compared with the approved dosage, which is PegIntron 1.0 microgram (mcg)/kg given once a week for 24 weeks. This study compares dosages of (1) 1.5 mcg/kg once a week for 24 weeks and (2) 1.5 mcg/kg once a week for 48 weeks with the approved dosage. All subjects are followed for 24 weeks after their treatment ends.
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 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
671 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PEG 1.0 mcg/kg weekly (QW) * 24 weeks
Arm Type
Active Comparator
Arm Description
PegIntron 1.0 mcg/kg weekly (QW) * 24 weeks + 24 weeks follow-up
Arm Title
PEG 1.5 mcg/kg QW * 24 wks
Arm Type
Experimental
Arm Description
PegIntron 1.5 mcg/kg QW * 24 wks + 24 wks follow-up
Arm Title
PEG 1.5 mcg/kg QW * 48 wks
Arm Type
Experimental
Arm Description
PegIntron 1.5 mcg/kg QW * 48 wks + 24 wks follow-up
Intervention Type
Drug
Intervention Name(s)
pegylated interferon alpha-2b
Intervention Description
1.0 mcg/kg subcutaneously (S.C.) QW for 24 weeks
Intervention Type
Drug
Intervention Name(s)
pegylated interferon alpha-2b
Intervention Description
1.5 mcg/kg S.C. QW for 24 weeks
Intervention Type
Drug
Intervention Name(s)
pegylated interferon alpha-2b
Intervention Description
1.5 mcg/kg S.C. QW for 48 weeks
Primary Outcome Measure Information:
Title
Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss
Description
HBeAg Loss was tested by Abbott Microparticle Enzyme Immunoassay (MEIA)
Time Frame
24 weeks after end of treatment (EOT)
Secondary Outcome Measure Information:
Title
Number of Participants With HBeAg Loss
Description
HBeAg Loss was tested by assay of Abbott MEIA
Time Frame
Up to Treatment Week 48
Title
HBe Seroconversion
Description
HBe seroconversion was defined as HBeAg Loss and Anti-HBeAg Positive. These were tested by assay of Abbott MEIA.
Time Frame
End of treatment (EOT) and 24 weeks after EOT
Title
Number of Participants With Hepatitis B Virus - Deoxyriboncleic Acid (HBV-DNA) <20,000 IU/mL
Description
HBV-DNA was tested by assay of Roche Cobas Taqman (the test
lowest limit is 6 IU/mL)
Time Frame
End of treatment (EOT) and 24 weeks after EOT
Title
Number of Participants With HBV-DNA < 200 IU/mL
Description
HBV-DNA was tested by assay of Roche Cobas Taqman (the test lowest limit is 6 IU/mL)
Time Frame
End of treatment (EOT) and 24 weeks after EOT
Title
Number of Participants With HBV-DNA Undetectable
Description
Undetectable HBV-DNA was defined as having a level <6 IU/mL by polymerase chain reaction (PCR).
Time Frame
End of treatment (EOT) and 24 weeks after EOT
Title
Number of Participants With Biochemical Response
Description
Biochemical response was defined as alanine aminotransferase (ALT) normalization.
Time Frame
End of treatment (EOT) and 24 weeks after EOT
Title
Number of Participants With Combined Response
Description
Combined response was defined as HBV DNA <20,000 IU/mL and HBe seroconversion and alanine aminotransferase (ALT) normalization
Time Frame
End of treatment (EOT) and 24 weeks after EOT
Title
Hepatitis B Surface Antigen (HBsAg) Loss
Description
HBsAg Loss was tested by assay of Abbott MEIA
Time Frame
End of treatment (EOT) and 24 weeks after EOT
Title
Hepatitis B Surface Antigen (HBs) Seroconversion
Description
HBs seroconversion was defined as having HBsAg Loss and Anti-HBs Positive
Time Frame
End of treatment (EOT) and 24 weeks after EOT
Title
Change From Baseline in Liver Biopsy Score
Description
Method for biopsy scoring was Knodell Scoring System (Histology Activity Index-HAI Score System):
Score I (periportal +/- bridging necrosis): 0 (none) to 10 (multilobular necrosis).
Score II (Intralobular degeneration and focal necrosis): 0 (none) to 4 (Marked [involvement of >2/3 of lobules or nodules]).
Score III (portal inflammation): 0 (none) to 4 (Marked [dense packing of
inflammatory cells in >2/3 of portal tracts]).
Score IV (fibrosis): 0 (none) to 4 (cirrhosis).
Time Frame
Baseline to 24 weeks after end of treatment
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:
Adults with chronic hepatitis B:
Serum hepatitis B surface antigen positive for at least 6 months
Serum hepatitis B e antigen positive
Serum negative for hepatitis B surface and e antibodies
Plasma hepatitis B virus deoxyribonucleic acid (DNA) level greater than 20,000 IU/mL
Alanine aminotransferase (ALT) 2- to 10-times the upper limit of normal
Compensated liver disease with certain minimum hematological and serum biochemical criteria
Exclusion Criteria:
Significant hepatic disease from an etiology other than hepatitis B virus
Antiviral treatment for hepatitis within previous 6 months
History of severe psychiatric disease, especially depression
Unstable or significant cardiovascular disease
Prolonged exposure to known hepatotoxins such as alcohol or drugs
Any condition that could interfere with the subject participating in and completing the study
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf
http://engagezone.msd.com/ds_documentation.php
Citations:
PubMed Identifier
25200354
Citation
Cheng J, Wang Y, Hou J, Luo D, Xie Q, Ning Q, Ren H, Ding H, Sheng J, Wei L, Chen S, Fan X, Huang W, Pan C, Gao Z, Zhang J, Zhou B, Chen G, Wan M, Tang H, Wang G, Yang Y, Mohamed R, Guan R, Lee TH, Chang WH, Zhenfei H, Ye Z, Xu D. Peginterferon alfa-2b in the treatment of Chinese patients with HBeAg-positive chronic hepatitis B: a randomized trial. J Clin Virol. 2014 Dec;61(4):509-16. doi: 10.1016/j.jcv.2014.08.008. Epub 2014 Aug 18.
Results Reference
result
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PegIntron Treatment of Chronic Hepatitis B e Antigen-Positive Patients (P05170/MK-4031-327)
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