A Multi-Center, Randomized, Open-Label, Phase IIIb Study Investigating the Safety and Efficacy of Peginterferon a-2a Plus Ribavirin for the Treatment of Chronic Hepatitis C Infection in HIV Infected Persons Who Have Failed to Achieve a Sustained Virologic Response Following Previous Interferon Therapy
Overview
- Phase
- Phase 3
- Intervention
- Not specified
- Conditions
- Chronic Hepatitis C Infection in HIV Infected Persons
- Sponsor
- Hepatitis Resource Network
- Locations
- 1
- Primary Endpoint
- 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
- Last Updated
- 20 years ago
Overview
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
Investigators
Eligibility Criteria
Inclusion Criteria
- •To be eligible for this trial, patients must have documentation of the following:
- •4.2.1 Written informed consent specific to this protocol obtained prior to screening and willingness to participate in and comply with the study.
- •4.2.2 Male and female patients \>18 years of age.
- •4.2.3 Detectable plasma HCV-RNA by RT-PCR or other assay (bDNA).
- •4.2.4 HCV genotype result must be available at screening (historical determinations of genotype are acceptable).
- •4.2.5 Evidence of HIV infection (reactive HIV antibody with Western blot confirmation).
- •4.2.6 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.
- •4.2.7 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.
- •4.2.8 No therapy with interferon or interferon plus ribavirin or other specific anti-HCV medications within 4 weeks of the screening.
- •4.2.9 Compensated liver disease with the following laboratory parameters at screening (results within 1 month of screening):
Exclusion Criteria
- •Patients meeting any of the following criteria are not eligible for this trial:
- •4.3.1 Inability or unwillingness to provide written informed consent specific to this protocol or unwillingness to participate in and comply with the study.
- •4.3.2 Women with ongoing pregnancy or breast feeding.
- •4.3.3 Male partners of women who are pregnant.
- •4.3.4 Hypersensitivity to interferon or ribavirin.
- •4.3.5 Evidence of advanced liver disease such as a history of or presence of ascites, bleeding varices, or spontaneous encephalopathy.
- •4.3.6 Any other causes for chronic liver disease other than chronic hepatitis C.
- •4.3.7 Hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia.
- •4.3.8 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.
- •4.3.9 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.
Outcomes
Primary Outcomes
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
- 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.