Clinical trial NCT00512278: Infliximab Treatment Along With Pegylated Interferon and Ribavirin in the Treatment of Hepatitis C
Official title: Infliximab (Remicade®) as an Adjunct to Pegylated- Interferon α-2b and Ribavirin in the Treatment of Hepatitis C Virus Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C
Keywords: Hepatitis
HCV
Hepatitis C
Lead sponsor: The Cleveland Clinic
Sponsor class: OTHER
Collaborators: name: Centocor, Inc.
First posted: 2007-08-07
Enrollment: 146
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: 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.
timeFrame: 72 Weeks from initiation of treatment
measure: Number of Participants Achieving Sustained Virological Response (SVR)
timeFrame: 24 weeks after completion of all study medications
Secondary outcomes:
measure: A Comparison of the Percentage of Participants With Non-detectable HCV-RNA After 24 Weeks of Therapy.
timeFrame: 24 weeks
measure: Percentage of Participants Experiencing Serious Adverse Events
timeFrame: 72 Weeks from initiation of treatment
measure: Percentage of Participants Experiencing Medically Significant Infections
timeFrame: 72 weeks from initiation of treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center, Center for Liver Disease and Transplantation
state: California
city: Port Orange
country: United States
facility: Advanced Medical Research Center
state: Florida
city: Louisville
country: United States
facility: University of Louisville
state: Kentucky
city: Cleveland
country: United States
facility: Case Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: The Liver Institute at Methodist Dallas
state: Texas
city: San Antonio
country: United States
facility: Brooke Army Medical Center
state: Texas
Study officials:
affiliation: The Cleveland Clinic
name: Nizar N Zein, MD
role: PRINCIPAL_INVESTIGATOR
References: