Back to resultsEfficacy of Peginterferon Alfa-2b in Previously Untreated Subjects With Chronic Hepatitis B and D Co-infection (Study P04603)
Primary Purpose
Hepatitis D, Chronic, Hepatitis B, Chronic
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Peginterferon alfa-2b (PegIntron, SCH 54031)
Sponsored by
About this trial
This is an interventional treatment trial for Hepatitis D, Chronic focused on measuring Hepatitis D, Hepatitis B
Eligibility Criteria
Inclusion Criteria:
- Participants must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
- Age 18-65 years old.
- HBsAg positive >6 months.
- ALT >= 2 ULN >6 months.
- HDV RNA positive serology.
- Serum antibody to hepatitis delta antigen of IgG and IgM class.
- Knodell score HAI >= 6 and F >= 0; positive test for intrahepatic Delta antigen in liver biopsy.
- Women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (e.g., hormonal contraceptive, medically prescribed IUD, condom in combination with spermicide) or be surgically sterilized (e.g., hysterectomy or tubal ligation).
- Participants must be free of any clinically significant disease (other than chronic hepatitis B and D), that would interfere with study evaluations.
- Participants must understand and be able to adhere to the dosing and visit schedules, and agree to record symptom severity scores, medication times, concomitant medications, and adverse events accurately and consistently in a daily diary.
Exclusion Criteria:
- Age <18 and >65.
- Concomitant HCV and/or HIV infection.
- Actual liver failure (total serum bilirubin >2.5 x normal, prolonged prothrombin time >3 sec, serum albumin <3 g/dl, history of ascites, variceal bleeding, or hepatic encephalopathy).
- Toxic or autoimmune hepatitis (ANA titers > 1:160), metabolic liver diseases (Wilson disease, hemochromatosis, α-1 antitrypsin deficiency)
- Women who are pregnant or nursing.
- Leukopenia (<2500/mm^3), neutropenia (<1000/mm^3), hemoglobin <10 g/dl, presence of other severe diseases (myocardiopathy, diabetes mellitus, arterial hypertension, neoplasia, neurologic diseases, malnutrition).
- Antiviral, immunomodulatory, corticosteroid, or chemotherapeutical treatment within 6 months of the participation in the study.
- Depression and/or psychiatric disorders.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
PegIntron
Arm Description
All participants received PegIntron (Peginterferon alfa-2b) weekly based on their body weight.
Outcomes
Primary Outcome Measures
Number of Participants With a Virological Response
For virological response, a participant was defined as a responder if his/her serum sample tested negative for Hepatitis D Virus - ribonucleic acid (HDV-RNA) by polymerase chain reaction (PCR) at end of treatment (EOT).
Number of Participants With a Biochemical Response
A participant was defined as a responder if his alanine aminotransferase (ALT) level after 52 weeks, i.e. at EOT, was below the upper reference range as specified by Bioclinica. The normal reference range for ALT is 5-55 U/L.
Number of Participants With a Combined Response
The combined response was defined as an ALT level below the upper
reference range and a negative HDV-RNA test. The normal reference range for ALT is 5-55 U/L.
Secondary Outcome Measures
Number of Participants With Hepatitis B Virus (HBV) Replication Response (HBV Response)
Serum samples collected from the participants were tested by PCR to detect HBV-DNA. HBV response was defined as the absence of HBV-deoxyribonucleic acid (HBV-DNA) in serum.
Number of Participants With a Liver Histology Response
The liver histology response was defined as at least a 2 point decrease in the necrosis inflammation score (a sum of periportal necrosis [0-10], lobular inflammation [0-4], portal inflammation [0-4], with the total score of 18 representing the worst outcome) and no increase or regression of fibrosis (scored [0-4]) in the pre- and post-treatment liver biopsies.
The efficacy of treatment based on histological response was assessed by the investigator as complete response, partial response, minimal response, progressive disease, and not assessable at EOT.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00686790
Brief Title
Efficacy of Peginterferon Alfa-2b in Previously Untreated Subjects With Chronic Hepatitis B and D Co-infection (Study P04603)
Official Title
An Open Label, Uncontrolled, Study to Assess the Response of Peg-Intron in naïve Patients With Chronic Hepatitis B and D Co-infection
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
December 2005 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 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 objective of this study is to determine the effectiveness of peginterferon alfa-2b 1.5 mcg/kg/week administered for 52 weeks (wk) in previously untreated participants coinfected with hepatitis virus B and D. After 52-week treatment and 52-week follow-up, the virologic, biochemical, and histological response will be evaluated.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis D, Chronic, Hepatitis B, Chronic
Keywords
Hepatitis D, Hepatitis B
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
PegIntron
Arm Type
Experimental
Arm Description
All participants received PegIntron (Peginterferon alfa-2b) weekly based on their body weight.
Intervention Type
Biological
Intervention Name(s)
Peginterferon alfa-2b (PegIntron, SCH 54031)
Other Intervention Name(s)
SCH 54031, PegIntron
Intervention Description
Peginterferon alfa-2b 1.5 mcg/kg/wk subcutaneously (SC) for 52 weeks.
Primary Outcome Measure Information:
Title
Number of Participants With a Virological Response
Description
For virological response, a participant was defined as a responder if his/her serum sample tested negative for Hepatitis D Virus - ribonucleic acid (HDV-RNA) by polymerase chain reaction (PCR) at end of treatment (EOT).
Time Frame
52 weeks (end of treatment [EOT]), 104 weeks (end of follow-up [EOF]) following treatment initiation
Title
Number of Participants With a Biochemical Response
Description
A participant was defined as a responder if his alanine aminotransferase (ALT) level after 52 weeks, i.e. at EOT, was below the upper reference range as specified by Bioclinica. The normal reference range for ALT is 5-55 U/L.
Time Frame
52 weeks (EOT), 104 weeks (EOF)
Title
Number of Participants With a Combined Response
Description
The combined response was defined as an ALT level below the upper
reference range and a negative HDV-RNA test. The normal reference range for ALT is 5-55 U/L.
Time Frame
52 weeks (EOT), 104 weeks (EOF)
Secondary Outcome Measure Information:
Title
Number of Participants With Hepatitis B Virus (HBV) Replication Response (HBV Response)
Description
Serum samples collected from the participants were tested by PCR to detect HBV-DNA. HBV response was defined as the absence of HBV-deoxyribonucleic acid (HBV-DNA) in serum.
Time Frame
52 week (EOT)
Title
Number of Participants With a Liver Histology Response
Description
The liver histology response was defined as at least a 2 point decrease in the necrosis inflammation score (a sum of periportal necrosis [0-10], lobular inflammation [0-4], portal inflammation [0-4], with the total score of 18 representing the worst outcome) and no increase or regression of fibrosis (scored [0-4]) in the pre- and post-treatment liver biopsies.
The efficacy of treatment based on histological response was assessed by the investigator as complete response, partial response, minimal response, progressive disease, and not assessable at EOT.
Time Frame
Baseline and 52 week (EOT)
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:
Participants must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
Age 18-65 years old.
HBsAg positive >6 months.
ALT >= 2 ULN >6 months.
HDV RNA positive serology.
Serum antibody to hepatitis delta antigen of IgG and IgM class.
Knodell score HAI >= 6 and F >= 0; positive test for intrahepatic Delta antigen in liver biopsy.
Women of childbearing potential (includes women who are less than 1 year postmenopausal and women who become sexually active) must be using an acceptable method of birth control (e.g., hormonal contraceptive, medically prescribed IUD, condom in combination with spermicide) or be surgically sterilized (e.g., hysterectomy or tubal ligation).
Participants must be free of any clinically significant disease (other than chronic hepatitis B and D), that would interfere with study evaluations.
Participants must understand and be able to adhere to the dosing and visit schedules, and agree to record symptom severity scores, medication times, concomitant medications, and adverse events accurately and consistently in a daily diary.
Exclusion Criteria:
Age <18 and >65.
Concomitant HCV and/or HIV infection.
Actual liver failure (total serum bilirubin >2.5 x normal, prolonged prothrombin time >3 sec, serum albumin <3 g/dl, history of ascites, variceal bleeding, or hepatic encephalopathy).
Toxic or autoimmune hepatitis (ANA titers > 1:160), metabolic liver diseases (Wilson disease, hemochromatosis, α-1 antitrypsin deficiency)
Women who are pregnant or nursing.
Leukopenia (<2500/mm^3), neutropenia (<1000/mm^3), hemoglobin <10 g/dl, presence of other severe diseases (myocardiopathy, diabetes mellitus, arterial hypertension, neoplasia, neurologic diseases, malnutrition).
Antiviral, immunomodulatory, corticosteroid, or chemotherapeutical treatment within 6 months of the participation in the study.
Depression and/or psychiatric disorders.
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
Learn more about this trial
Efficacy of Peginterferon Alfa-2b in Previously Untreated Subjects With Chronic Hepatitis B and D Co-infection (Study P04603)
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