PEG-Interferon a-2b + Ribavirin for Treatment of Patients With Chronic Hepatitis C Who Have Previously Failed to Achieve a Sustained Virologic Response Following Interferon Alfa or Interferon a-2b + Ribavirin Therapy

NCT00215865 | Completed Phase 3

• 1 other identifier: HRN 003
• Study Type: interventional
• Target: 600
• Locations: 1 country
• Sites: 1

Brief Summary

HRN-003 STUDY SYNOPSIS OBJECTIVE: To compare the Sustained Virologic Response (SVR) of PEGIntron plus ribavirin among patients receiving a fixed dose of PEGIntron versus weighted-adjusted dosing. OVERVIEW OF STUDY DESIGN: This is a multi-center, randomized, open-label clinical trial using PEGIntron weight-adjusted dose by subcutaneous injection weekly + ribavirin by mouth twice daily for 48 weeks OR PEGIntron fixed dose by subcutaneous injection weekly + ribavirin by mouth twice daily for 48 weeks. STUDY POPULATION: 600 Adult patients with chronic hepatitis C virus infection who have previously failed to achieve a sustained virologic response following interferon alfa or interferon alfa-2b plus ribavirin therapy. DOSAGE AND ADMINISTRATION: Eligible participants will be randomized to receive PEGIntron weight-adjusted dose (1.5 mg/kg) by subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for 48 weeks OR PEGIntron fixed dose (150 mg if weight \> than 80 kg or 100 mg if weight \< 80 KG) by subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for 48 weeks. EFFICACY EVALUATIONS: Laboratory analysis, quality of life assessments, and change in study medication doses will be obtained. SAFETY EVALUATIONS: Assessment of laboratory evaluations, vital signs, incidence and severity of adverse experiences and progression of disease, as measured by HCV viral load. STUDY DESIGN This is a treatment protocol to evaluate the antiviral efficacy, safety and tolerability polyethylene glycol (PEG) conjugated interferon alfa-2b (PEGIntron) for the treatment of chronic hepatitis C virus infection in patients who have previously failed to achieve a sustained virologic response following interferon alfa or interferon alfa-2b plus ribavirin therapy. Patients will be stratified according to their response to the previous course of therapy (i.e. non-reponse or relapse virologic pattern This is a multi-center, randomized, open-label clinical trial that will involve approximately 25 sites with an anticipated enrollment of 600 patients over a six-month period. Eligible participants will be randomized to receive PEGIntron weight-adjusted dose (1.5 mg/kg) by subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for 48 weeks OR PEGIntron fixed dose (150 mg if weight \> than 80 kg or 100 mg if weight \< 80 KG) by subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for 48 weeks.

• Group A: PEGIntron weight -adjusted dose (1.5 mg/kg) by subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for 48 weeks (Total therapy x 48weeks).
• Group B: PEGIntron fixed dose (150 mg if weight \> than 80 kg or 100 mg if weight \< 80 KG) by subcutaneous injection weekly + ribavirin 400 mg by mouth twice daily for an additional 48 weeks (Total therapy x 48 weeks).

Conditions

Chronic Hepatitis C Virus Infection

Outcome Measures

Primary Outcomes (1)

• 1. To compare the Sustained Virologic Response (SVR) of PEGIntron plus ribavirin among patients receiving a fixed dose of PEGIntron versus weighted-adjusted dosing

Secondary Outcomes (2)

• 2. To evaluate the safety and tolerability PEG Intron in combination with ribavirin given as a fixed dose versus weight adjusted.

• 3. To determine the Early Virologic Response (EVR) at week 24.

Interventions

PEGIntron plus ribavirin DRUG

Eligibility Criteria

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

You may qualify if:

• The patient must meet the following criteria for entry:
• Adult male or female, age of 18 or older.
• Serums positive for hepatitis C virus by RT-PCR or other assay (bDNA).
• HCV genotype result must be available at screening.
• Previous antiviral therapy with interferon or interferon plus ribavirin for at least 12 weeks with the failure to obtain a sustained virologic response.
• No therapy with interferon alfa or interferon alfa-2b plus ribavirin or other specific anti-HCV medications within 6 weeks of the Entry visit.
• Compensated liver disease with the following laboratory parameters at the Entry visit:
• Hemoglobin values of ³ 12 gm/dL for females or ³ 13 gm/dL for males
• WBC ³ 3,000/mm3
• Neutrophil count ³1,500/mm3
• Platelets ³ 70,000/mm3
• Prothrombin time \< 2 seconds prolonged compared to control, or equivalent INR ratio
• Bilirubin within 20% of the upper limit of normal (unless non-hepatitis related factors such as Gilbert's disease explains an indirect bilirubin rise).
• Albumin \> 3.0 g/dL (or within 20% of LLN)
• Serum creatinine \< 1.4 mg/dL

You may not qualify if:

• The patient will be excluded from entry if any of the following criteria apply:
• Hypersensitivity to alpha interferon or ribavirin.
• Any other causes for chronic liver disease other than chronic hepatitis C.
• Hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia.
• Evidence of advanced liver disease such as a history of or presence of ascites, bleeding varices, or spontaneous encephalopathy.
• Any known preexisting medical condition that could interfere with the patient s participation in the protocol including: CNS trauma or active seizure disorders requiring medication; poorly controlled diabetes mellitus; serious pulmonary disease; immunologically-mediated diseases; gout; or any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids.
• Patients with evidence of ischemia on stress testing (required for patients at risk of or with a history of coronary artery disease), ECG evidence of ischemia, an arrhythmia, cardiac failure, coronary surgery, uncontrolled hypertension, angina or a myocardial infarction within 12 months.
• Patients with clinically significant retinal abnormalities.
• Patients with an alcohol consumption of \> 20 gm/day are ineligible for the protocol. Patients must be counseled with regard to the need to abstain from the consumption of alcohol.
• Concurrent use of nucleoside analogs, amantadine/rimantadine, and HIV protease inhibitors will be excluded.
• Patients with a history of organ transplantation will be excluded.
• Preexisting psychiatric conditions; especially depression, or a history of severe psychiatric disorder, such as major psychoses, suicidal ideation and/or suicidal attempt are excluded. Patients with a history of mild depression may enter the protocol if they meet the following eligibility criterion and are monitored as outlined in Section 11.2 (Management of Depression During Study).
• Mild depression: to include either situational depression of a limited period or depressive symptoms, which do not significantly interfere with the patients work or daily functions. Any patient with a manic element to his/her previous symptom complex will be excluded.
• Detailed follow-up of each patient may be individualized according to his/her need; this would usually include further predetermined visits. Patients with a history of mild depression or patients undergoing successful treatment for mild depression will be managed as outlined in Section 11.2 (Management of Depression During Study).

Sponsors & Collaborators

• Hepatitis Resource Network: lead
• Hoffmann-La Roche: collaborator

Study Sites (1)

Johns Hopkins Univesity School of Medicine

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Interventions

peginterferon alfa-2b; Ribavirin

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Mark Sulkowski, MD

  Hepatitis Resource Network

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 20, 2005
• First Posted: September 22, 2005
• Last Updated: September 22, 2005

Record last verified: 2005-09

Locations

US (1)