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

Phase 2

Completed

Conditions: Hepatitis C

Interventions: Drug: Placebo
Drug: Infliximab

Registration Number: NCT00512278

Lead Sponsor: Nizar Zein

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

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 146

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo: 48 weeks of therapy with Placebo and PEG INF-2b/RBV
Infliximab	Infliximab	Infliximab: 48 weeks of therapy with the combination of PEG INF-2b/RBV plus adjuvant infliximab

Primary Outcome Measures

Name	Time	Method
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.	72 Weeks from initiation 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
Number of Participants Achieving Sustained Virological Response (SVR)	24 weeks after completion of all study medications	HCV RNA negativity at 24 weeks after completion of all study medications

Secondary Outcome Measures

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

Trial Locations

Locations (7): Cedars-Sinai Medical Center, Center for Liver Disease and Transplantation
🇺🇸
Los Angeles, California, United States
Case Medical Center
🇺🇸
Cleveland, Ohio, United States
Cleveland Clinic
🇺🇸
Cleveland, Ohio, United States
Brooke Army Medical Center
🇺🇸
San Antonio, Texas, United States
Advanced Medical Research Center
🇺🇸
Port Orange, Florida, United States
University of Louisville
🇺🇸
Louisville, Kentucky, United States
The Liver Institute at Methodist Dallas
🇺🇸
Dallas, Texas, United States