PegIntron Treatment of Chronic Hepatitis B e Antigen-Positive Patients (P05170/MK-4031-327)

Hepatitis B, Chronic Clinical Trial

Official title:

An Open-label, Randomized Study of PegIntron in the Treatment of HBeAg Positive Chronic Hepatitis B Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00536263
• Other study ID #: P05170
• Status: Completed
• Phase: Phase 3
• First received: September 26, 2007
• Last updated: February 25, 2015
• Start date: September 2007
• Est. completion date: November 2009

Study information

• Verified date: February 2015
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 671
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• pegylated interferon alpha-2b
1.0 mcg/kg subcutaneously (S.C.) QW for 24 weeks
• pegylated interferon alpha-2b
1.5 mcg/kg S.C. QW for 24 weeks
• pegylated interferon alpha-2b
1.5 mcg/kg S.C. QW for 48 weeks

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Hepatitis B Envelope Antigen (HBe or HBeAg) Loss	HBeAg Loss was tested by Abbott Microparticle Enzyme Immunoassay (MEIA)	24 weeks after end of treatment (EOT)	No
Secondary	Number of Participants With HBeAg Loss	HBeAg Loss was tested by assay of Abbott MEIA	Up to Treatment Week 48	No
Secondary	HBe Seroconversion	HBe seroconversion was defined as HBeAg Loss and Anti-HBeAg Positive. These were tested by assay of Abbott MEIA.	End of treatment (EOT) and 24 weeks after EOT	No
Secondary	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)	End of treatment (EOT) and 24 weeks after EOT	No
Secondary	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)	End of treatment (EOT) and 24 weeks after EOT	No
Secondary	Number of Participants With HBV-DNA Undetectable	Undetectable HBV-DNA was defined as having a level <6 IU/mL by polymerase chain reaction (PCR).	End of treatment (EOT) and 24 weeks after EOT	No
Secondary	Number of Participants With Biochemical Response	Biochemical response was defined as alanine aminotransferase (ALT) normalization.	End of treatment (EOT) and 24 weeks after EOT	No
Secondary	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	End of treatment (EOT) and 24 weeks after EOT	No
Secondary	Hepatitis B Surface Antigen (HBsAg) Loss	HBsAg Loss was tested by assay of Abbott MEIA	End of treatment (EOT) and 24 weeks after EOT	No
Secondary	Hepatitis B Surface Antigen (HBs) Seroconversion	HBs seroconversion was defined as having HBsAg Loss and Anti-HBs Positive	End of treatment (EOT) and 24 weeks after EOT	No
Secondary	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).	Baseline to 24 weeks after end of treatment	No