Effect of Infliximab on the Efficacy of Peg-Intron/Ribavirin in Patients With Hepatitis C (Study P04257AM4)(COMPLETED)

NCT00237484 | Completed Phase 3

• 1 other identifier: P04257
• Study Type: interventional
• Target: 89
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is a Phase IIIB, randomized, prospective, multicenter, single-country, open-label, controlled pilot trial designed to evaluate the effect of infliximab induction therapy on sustained virologic response (SVR) to treatment with pegylated interferon alfa-2b plus ribavirin in a group of 96 therapy-naïve subjects with genotype 1 hepatitis C virus (HCV) infection and high serum tumor necrosis factor (TNF)-alpha values.

Conditions

Hepatitis C, Chronic

Keywords

pegylated interferon alfa-2b; ribavirin; infliximab; chronic hepatitis C

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects who have achieved sustained virological response (SVR) in the infliximab (induction dose) plus PEGETRON and the PEGETRON groups at 24 weeks post treatment end

  24 weeks after completion of up to 48 weeks of PEGETRON therapy

Secondary Outcomes (2)

• Early virological response (EVR)

  Week 12 of PEGETRON treatment period

• Safety parameters

  During 48-week PEGETRON treatment period and 24-week follow up

Study Arms (2)

Arm A

EXPERIMENTAL

Remicade induction dose at Day -7 prior to initiation of PEGETRON treatment for up to 48 weeks

Drug: Induction dose of (a) infliximab followed by combination of (b) pegylated interferon alfa-2b and (c) ribavirin

Arm B

ACTIVE COMPARATOR

PEGETRON treatment for up to 48 weeks

Drug: Combination of (a) pegylated interferon alfa-2b and (b) ribavirin

Interventions

Induction dose of (a) infliximab followed by combination of (b) pegylated interferon alfa-2b and (c) ribavirin DRUG

1. Powder for intravenous infusion (100 mg strength), intravenous, single dose of 5 mg/kg, at Day -7, prior to initiation of the following combination therapy: 2. powder for injection in vials or Redipen (80, 100, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 48 weeks 3. 200 mg capsules, oral, dose of 800-1400 mg (weight based dosing as per PEGETRON Product Monograph), daily for up to 48 weeks

Also known as: (a) SCH 215596, Remicade, PEGETRON combination therapy, (b) SCH 54031, PEG-Intron, PegIntron, (c) SCH 18908, REBETOL

Arm A

Combination of (a) pegylated interferon alfa-2b and (b) ribavirin DRUG

1. Powder for injection in vials or Redipen (80, 100, 120, and 150 microgram strengths), subcutaneous, dose of 1.5 micrograms/kg, weekly for up to 48 weeks 2. 200 mg capsules, oral, dose of 800-1400 mg (weight based dosing as per PEGETRON Product Monograph), daily for up to 48 weeks

Also known as: PEGETRON combination therapy, (a) SCH 54031, PEG-Intron; PegIntron, (b) SCH 18908, REBETOL

Arm B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must demonstrate their willingness to participate in the study and comply with its procedures by signing a written informed consent.
• Subjects must be 18 to 65 years of age.
• HCV genotype 1 (including mixtures of subtypes of genotype 1).
• Naïve to interferon (any formulation) and ribavirin.
• Serum TNF-alpha \>300 pg/mL(single measure at Pre-Screen Visit).
• HCV ribonucleic acid (RNA) positive.
• Any alanine aminotransferase (ALT) level.
• Fasting glucose should be 3.8-6.2 mmol/L. Results between 6.3-7.8 mmol/L require a HbA1c \<=8.5%. All diabetic subjects must have an HbA1c \<=8.5%, whether on medication or diet controlled.
• Liver biopsy within 24 months of enrolment demonstrating Stage 0-3 fibrosis (Metavir System).
• Compensated liver disease with the following minimum hematological, biochemical, and serological criteria at the screen visit (WNL = within normal limits):
• Hemoglobin values of equal or more than 12 g/dL for females and 13 g/dL for males.
• White blood cell (WBC) count equal to or more than 3,000/mm\*\*3
• Neutrophil count equal to or more than 1,500/mm\*\*3
• Platelet count equal to or more than 80,000/mm\*\*3
• Total bilirubin WNL

You may not qualify if:

• Women who are pregnant or nursing.
• Subjects who have not observed the designated washout periods for any of the prohibited medications.
• Subjects who have used any investigational product within 30 days prior to enrollment.
• Acute HCV infection defined as infection for \<6 months.
• Male partners to/or Heterosexually active women of childbearing potential not practicing a highly effective form of contraception.
• Positive screening for tuberculosis (TB) or Tuberculin Skin Test \> 5mm.
• History or presence of cirrhosis (Stage 4 on Metavir System) and/or complication such as ascites, bleeding varices or hepatic encephalopathy
• Active hepatitis B virus (HBV) infection (hepatitis B surface antigen \[HBsAg\] positive).
• Any known pre-existing psychiatric condition that could interfere with the subject's participation in and completion of the study such as:
• Pre-existing psychiatric condition, including but not limited to moderate to severe depression, or a history of severe psychiatric disorders, such as psychosis, suicidal ideation and/or suicidal attempt
• Severe depression includes the following:
• Hospitalization for depression,
• Electro convulsive therapy for depression, or
• Depression that resulted in a prolonged absence from work and/or significant disruption of daily functions.
• Subjects with uncontrolled hypertension and/or diabetes.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

peginterferon alfa-2b; Ribavirin; Infliximab

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2005
• First Posted: October 12, 2005
• Study Start: July 18, 2005
• Primary Completion: June 30, 2011
• Study Completion: June 30, 2011
• Last Updated: August 26, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will share