Infliximab Treatment Along With Pegylated Interferon and Ribavirin in the Treatment of Hepatitis C

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to investigate in subjects receiving their first course of peg-interferon α-2b plus ribavirin therapy for chronic HCV infection

Detailed Description
-----------------
The aim of the study is to investigate in subjects receiving their first course of peg-interferon α-2b plus ribavirin therapy for chronic HCV infection (genotype 1) whether the addition of infliximab to a standard regimen of pegylated interferon α-2b in combination with ribavirin: increases the proportion of subjects attaining a sustained virological response SVR (undetectable blood Hepatitis C viral load 6 months after treatment) improves the safety profile compared to the same regimen without infliximab

Official Title
-----------------
Infliximab (Remicade®) as an Adjunct to Pegylated- Interferon α-2b and Ribavirin in the Treatment of Hepatitis C Virus Infection

Conditions
-----------------
Hepatitis C

Intervention / Treatment
-----------------
* Drug: Infliximab
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects, >18 years of age with proven chronic (greater than 6 months) hepatitis C infection (genotype 1) who have never been treated with pegylated interferon α-2b and /or ribavirin. Criteria for inclusion in this trial are as follows: Male or female, 18 years of age or older Positive HCV RNA, Genotype 1, treatment naïve (never received pegylated interferon and / or ribavirin) Evidence of chronic HCV infection for at least six months prior to screening Findings on liver biopsy within the past 36 months that are consistent with the presence of chronic hepatitis C infection. Negative hepatitis B surface antigen No evidence of hemochromatosis Hemoglobin ≥12 g/dL for females and ≥13 g/dL for males WBC ≥3.0 x 109/L and neutrophils ≥1.5 x 109/L Platelets ≥80 x109/L Direct Bilirubin WNL +/- 50% of central laboratory normal range. Total bilirubin ≤1.6. Albumin within normal limits Serum creatinine within normal limits. Serum thyroid stimulating hormone (TSH) levels within normal limits Men and women of childbearing potential must use two forms of adequate birth control measures for the duration of the study and should continue such precautions for 6 months after receiving the last infusion. Subjects with a history of mild depression may be considered for entry into this study. No history of latent or active TB. Exclusion Criteria: Women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion and men with partners who are pregnant at baseline or intend to become pregnant within 6 months after the last infusion. Known allergy against infliximab, ribavirin, or pegylated interferon Decompensated liver disease characterized as decreased hepatic synthetic functioning with abnormal albumin and bilirubin levels, prolonged prothrombin time or complications including ascites or recent variceal bleeding have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidiomycosis (Valley Fever) History of autoimmune hepatitis or a history of poorly controlled autoimmune disease Use of other systemic anti-inflammatory medication except NSAIDs and low dose systemic steroids Previous treatment with monoclonal antibodies or antibody fragments History of receiving human/murine recombinant products or a known allergy to murine products Documentation of seropositive for human immunodeficiency virus (HIV) History of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results History of serious infections (e.g., hepatitis, pneumonia or pyelonephritis) in the previous 3 months Opportunistic infection within 6 months prior to screening History of lymphoproliferative disease Currently have any known malignancy or have a history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence Current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease Treatment with any other therapeutic agent targeted at reducing TNF within 3 months of screening Presence of a transplanted solid organ Concomitant diagnosis or history of congestive heart failure

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

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Infliximab<br>Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab | Drug: Infliximab<br>* Infliximab weight based injection at baseline, weeks 2,6,14,22,30,38,46<br>* Other names: Remicade;|
| Placebo Comparator: Placebo<br>Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV | Drug: Placebo<br>* Placebo<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A Comparison of the Percentage of Chronic Hepatitis C Subjects (Treatment Naive,Genotype 1) Who Achieve SVR at Week 72, After 48 Weeks of Treatment. | A comparison of the Proportion of Chronic Hepatitis C Subjects (Treatment Naive,Genotype 1) Who Achieve SVR at Week 72, After 48 Weeks of TreatmentSVR in both study arms | 72 Weeks from initiation of treatment | 
| Number of Participants Achieving Sustained Virological Response (SVR) | HCV RNA negativity at 24 weeks after completion of all study medications | 24 weeks after completion of all study medications | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A Comparison of the Percentage of Participants With Non-detectable HCV-RNA After 24 Weeks of Therapy. | A comparison of the proportion of the subject population with non-detectable HCV-RNA after 24 wks of therapy. | 24 weeks | 
| Percentage of Participants Experiencing Serious Adverse Events | The severity of adverse events was graded according to modified World Health Organization grades as mild, moderate, severe, or life-threatening | 72 Weeks from initiation of treatment | 
| Percentage of Participants Experiencing Medically Significant Infections | Medically significant infection was defined as an infection requiring the use of intravenous antibiotics or hospitalization. | 72 weeks from initiation of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HCV, Hepatitis, Hepatitis C