HRN 004- Peginterferon a-2a Plus Ribavirin for Chronic Hepatitis C Infection in HIV Infected Persons Who Have Failed to Achieve a Sustained Virologic Response Following Previous Interferon Therapy

NCT00215839 | Unknown Phase 3

• 1 other identifier: HRN 004
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: Primary To evaluate the safety, tolerability, and efficacy of Peginterferon a-2a plus Ribavirin for the treatment of chronic hepatitis C (CHC) infection in persons co-infected with human immunodeficiency virus (HIV) who have failed to achieve a sustained virologic response following previous interferon therapy. Secondary

• To evaluate the virological response to Peginterferon a-2a plus Ribavirin at weeks 12 and 24 as compared to baseline values.
• To evaluate the sustained virological response Peginterferon a-2a plus Ribavirin at post-treatment weeks 4, 12, and 24 as compared to baseline.
• To evaluate the histological effects of long-term Peginterferon a-2a therapy through comparison of liver biopsy results following 96 weeks of Peginterferon a-2a therapy to baseline values.
• To evaluate the safety and tolerability of long-term Peginterferon a-2a therapy in patients who have previously failed to achieve a sustained virologic response following interferon therapy.
• To investigate the effects of long-term Peginterferon a-2a therapy on clinical outcomes of HIV disease. Study Design: All qualifying patients will enter the treatment phase and be dosed as follows: Peginterferon a-2a 180mg by subcutaneous route once weekly plus Ribavirin:
• 800 mg (400 mg bid) if body weight \< 65 kg
• 1000 mg (400 mg a.m. and 600 mg p.m.) if body weight \> 65 kg and \< 85 kg
• 1200 mg (600 mg bid) if body weight \> 85 kg Patients with undetectable levels of HCV-RNA at Treatment Week 24 will continue on previously assigned Peginterferon a-2a plus Ribavirin combo-therapy for an additional 24 weeks. Patients with detectable levels of HCV-RNA will be randomized to Peginterferon a-2a mono-therapy or no treatment for 72 weeks.
• Group A: Peginterferon a-2a 90mg mono-therapy for 72 weeks.
• Group B: No CHC therapy for 72 weeks All patients entering the study are required to have a baseline liver biopsy (within 18 months of study entry). Patients entering the 72-week randomized arm of the trial will have a post-study liver biopsy upon completion of the trial. Study Population: 100 HIV infected adults with chronic hepatitis C infection who have failed to achieve a sustained virologic response following previous interferon therapy. Dosage and Administration: Combo-therapy: Peginterferon a-2a 180mg by subcutaneous route once weekly plus Ribavirin:
• 800 mg (400 mg bid) if body weight \< 65 kg
• 1000 mg (400 mg a.m. and 600 mg p.m.) if body weight \> 65 kg and \< 85 kg
• 1200 mg (600 mg bid) if body weight \> 85 kg Mono-therapy: Peginterferon a-2a 90mg in 1mL solution administered subcutaneously once weekly. Efficacy Evaluations: Laboratory analysis, liver biopsies, quality of life assessments, and changes in Peginterferona-2a and Ribavirin dosages will be obtained. Safety Evaluations:
• Assessment of laboratory evaluations
• vital signs
• incidence and severity of adverse experiences
• dose adjustments
• premature withdrawal for safety reasons
• progression of disease as measured by HCV viral load
• AIDS defining events

Conditions

Chronic Hepatitis C Infection in HIV Infected Persons; HIV Infections

Keywords

Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• evaluate the safety, tolerability, and efficacy of Peginterferon a-2a plus Ribavirin for the treatment of chronic hepatitis C (CHC) infection in persons co-infected with human immunodeficiency virus (HIV) who have failed to achieve a sustained virologi

Secondary Outcomes (2)

• To evaluate the virological response at weeks 12 and 24 as compared to baseline values.

• To evaluate the sustained virological response at post-treatment weeks 4, 12, and 24 as compared to baseline.

Interventions

Peginterferon a-2a 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:

• To be eligible for this trial, patients must have documentation of the following:
• Written informed consent specific to this protocol obtained prior to screening and willingness to participate in and comply with the study.
• Male and female patients \>18 years of age.
• Detectable plasma HCV-RNA by RT-PCR or other assay (bDNA).
• HCV genotype result must be available at screening (historical determinations of genotype are acceptable).
• Evidence of HIV infection (reactive HIV antibody with Western blot confirmation).
• Chronic liver disease consistent with chronic hepatitis C infection on a biopsy, as judged by a qualified pathologist, obtained within the past 18 months. For all participants, both the liver biopsy report and the biopsy specimen (both an H and E slide and a Trichrome slide) must be made available for review by the central pathologist.
• Previous antiviral treatment with alfa interferon monotherapy or, or interferon alfa plus ribavirin combination therapy administered for at least 12 weeks with the failure to obtain a sustained virologic response.
• No therapy with interferon or interferon plus ribavirin or other specific anti-HCV medications within 4 weeks of the screening.
• Compensated liver disease with the following laboratory parameters at screening (results within 1 month of screening):
• Hemoglobin values of ³ 11 gm/dL
• WBC ³ 3,000/mm3
• Neutrophil count ³1,250/mm3
• Platelets ³ 70,000/mm3
• Prothrombin time £ 3 seconds prolonged compared to control, or equivalent INR ratio

You may not qualify if:

• Patients meeting any of the following criteria are not eligible for this trial:
• Inability or unwillingness to provide written informed consent specific to this protocol or unwillingness to participate in and comply with the study.
• Women with ongoing pregnancy or breast feeding.
• Male partners of women who are pregnant.
• Hypersensitivity to interferon or ribavirin.
• Evidence of advanced liver disease such as a history of or presence of ascites, bleeding varices, or spontaneous encephalopathy.
• Any other causes for chronic liver disease other than chronic hepatitis C.
• Hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia.
• 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.
• Active or acute HIV-related opportunistic infection.
• Evidence of severe retinopathy (e.g. CMV retinitis, macular degeneration)
• History of major organ transplantation with an existing functional graft (including Bone Marrow Transplants)
• History of any systemic anti-neoplastic or immunomodulatory treatment (including supraphysiologic doses of steroids and radiation) £6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
• Concomitant medication with, rifampin/rifampicin, rifabutin, pyrazinamide, isoniazid, ganciclovir, thalidomide, oxymetholone (Anadrolâ), and immunomodulatory treatments (including supraphysiologic doses of steroids).

Sponsors & Collaborators

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

Study Sites (1)

Mt. Sinai School of Medicine

New York, New York, 10029, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Douglas Dieterich, MD

  Chair - 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: October 25, 2005

Record last verified: 2005-09

Locations

US (1)