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

Study Overview
=================
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.

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

Conditions
-----------------
Hepatitis D, Chronic, Hepatitis B, Chronic

Intervention / Treatment
-----------------
* Biological: Peginterferon alfa-2b (PegIntron, SCH 54031)


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PegIntron<br>All participants received PegIntron (Peginterferon alfa-2b) weekly based on their body weight. | Biological: Peginterferon alfa-2b (PegIntron, SCH 54031)<br>* Peginterferon alfa-2b 1.5 mcg/kg/wk subcutaneously (SC) for 52 weeks.<br>* Other names: SCH 54031, PegIntron;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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). | 52 weeks (end of treatment [EOT]), 104 weeks (end of follow-up [EOF]) following treatment initiation | 
| 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. | 52 weeks (EOT), 104 weeks (EOF) | 
| 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. | 52 weeks (EOT), 104 weeks (EOF) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 52 week (EOT) | 
| 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. | Baseline and 52 week (EOT) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Hepatitis D, Hepatitis B