Efficacy of Peginterferon Alfa-2b in Previously Untreated Subjects With Chronic Hepatitis B and D Co-infection (Study P04603)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00686790
Recruitment Status : Completed
First Posted : May 30, 2008
Results First Posted : January 17, 2011
Last Update Posted : April 6, 2017
Information provided by (Responsible Party):
Merck Sharp & Dohme Corp.

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.

Condition or disease Intervention/treatment Phase
Hepatitis D, Chronic Hepatitis B, Chronic Biological: Peginterferon alfa-2b (PegIntron, SCH 54031) Phase 3

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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 Start Date : December 2005
Actual Primary Completion Date : May 2009
Actual Study Completion Date : May 2009

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: PegIntron
All participants received PegIntron (Peginterferon alfa-2b) weekly based on their body weight.
Biological: Peginterferon alfa-2b (PegIntron, SCH 54031)
Peginterferon alfa-2b 1.5 mcg/kg/wk subcutaneously (SC) for 52 weeks.
Other Name: SCH 54031, PegIntron

Primary Outcome Measures :
  1. Number of Participants With a Virological Response [ Time Frame: 52 weeks (end of treatment [EOT]), 104 weeks (end of follow-up [EOF]) following treatment initiation ]
    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).

  2. Number of Participants With a Biochemical Response [ Time Frame: 52 weeks (EOT), 104 weeks (EOF) ]
    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.

  3. Number of Participants With a Combined Response [ Time Frame: 52 weeks (EOT), 104 weeks (EOF) ]

    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 :
  1. Number of Participants With Hepatitis B Virus (HBV) Replication Response (HBV Response) [ Time Frame: 52 week (EOT) ]
    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.

  2. Number of Participants With a Liver Histology Response [ Time Frame: Baseline and 52 week (EOT) ]

    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.

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Responsible Party: Merck Sharp & Dohme Corp. Identifier: NCT00686790     History of Changes
Other Study ID Numbers: P04603
First Posted: May 30, 2008    Key Record Dates
Results First Posted: January 17, 2011
Last Update Posted: April 6, 2017
Last Verified: March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

Keywords provided by Merck Sharp & Dohme Corp.:
Hepatitis D
Hepatitis B

Additional relevant MeSH terms:
Hepatitis D, Chronic
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis D
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Parasitic Diseases
Peginterferon alfa-2b
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs