Overview

This trial is active, not recruiting.

Conditions chronic hepatitis c infection in hiv infected persons, hiv infections
Treatment peginterferon a-2a plus ribavirin
Phase phase 3
Sponsor Hepatitis Resource Network
Collaborator Hoffmann-La Roche
Trial identifier NCT00215839, HRN 004

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

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment

Primary Outcomes

Measure
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
time frame:

Secondary Outcomes

Measure
To evaluate the virological response at weeks 12 and 24 as compared to baseline values.
time frame:
To evaluate the sustained virological response at post-treatment weeks 4, 12, and 24 as compared to baseline.
time frame:

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria

  • 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
  • Bilirubin within 20% of the upper limit of normal (unless non-hepatitis related factors such as Gilbert's disease or the use of indinivir explains an indirect bilirubin rise).
  • Albumin ³ 3.0 g/dL
  • Serum creatinine £ 1.4 mg/dL
  • Fasting blood sugar £ 115 mg/dL for non-diabetic patients
  • Hemoglobin A1C £ 8.5% for diabetic patients (whether on medication and/or diet controlled) 4.2.10 Thyroid Stimulating Hormone (TSH) within normal limits or thyroid disease under clinical control (within 3 months of screening) 4.2.11 Alpha-fetoprotein (AFP) value within normal limits obtained within the prior year. For patients with results above the upper limit of normal but < 100 ng/mL both of the following are required:
  • Alpha-fetoprotein value < 100 ng/mL obtained within 3 months prior to entry AND
  • Ultrasound obtained within 3 months prior to entry that is negative for evidence of hepatocellular carcinoma. 4.2.12 CD4 T cell count and HIV RNA level (by RT-PCR) within 4 weeks of screening:
  • CD4 <100 Eligible with HIV RNA <25,000 by RT-PCR
  • CD4 > 100 - Eligible with any HIV RNA level by RT-PCR 4.2.13 Stable antiretroviral regimen of FDA-approved agents for at least 4 weeks prior to baseline or has taken no antiretroviral agents within 4 weeks prior to baseline. 4.2.14 Reconfirmation and documentation that all sexually active female patients of childbearing potential are practicing adequate contraception (intrauterine device, oral contraceptives, progesterone implanted rods [Norplant], medroxyprogesterone acetate [Depo-Provera], surgical sterilization, barrier method [diaphragm + spermicide], or monogamous relationship with a male partner who has had a vasectomy or is using a condom + spermicide) during the treatment period and for 6 months after discontinuation of therapy. Female patients must not breast feed during the treatment period and for 6 months after discontinuation of therapy. A urine pregnancy test obtained at entry prior to the initiation of treatment must be negative. 4.2.15 Reconfirmation and documentation that sexually active male patients are practicing acceptable methods of contraception (vasectomy, use of a condom + spermicide, monogamous relationship with a female partner who practices an acceptable method of contraception) during the treatment period and for 6 months after discontinuation of therapy. 4.2.16 Anyone at high risk of coronary artery disease should have a stress test performed prior to entry. This would include, but not be limited to, patients over age 55 who have a history of ischemia or who have a significant history of hypertension, diabetes mellitus, obesity, smoking and/or strong family history of coronary artery disease. Patients with evidence of ischemia on resting or stress EKG, or a history of an arrhythmia, angina or a myocardial infarction within 12 months must be excluded.

Exclusion Criteria

    Additional Information

    Official title 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
    Principal investigator Douglas Dieterich, MD
    Trial information was received from ClinicalTrials.gov and was last updated in October 2005.
    Information provided to ClinicalTrials.gov by Hepatitis Resource Network.