Peginterferon and Ribavirin, With or Without Telaprevir, for Genotype 1 Hepatitis C and IL28B CC Polymorphism

• Status: Withdrawn
• Trial end date: 2011-07-01
• Target enrollment: 0
• Participant gender: All

Summary

Chronic hepatitis C is a major cause of liver disease and is thus an important public health problem. Although some strains (genotypes) of the hepatitis C virus are highly responsive to treatment with a combination of peginterferon and ribavirin, the most common form of the virus (genotype 1) is relatively resistant to this treatment. Recently, telaprevir has been approved by the Food and Drug Administration to be given in combination with peginterferon and ribavirin. This 3-drug combination boosts the remission rate for genotype 1 hepatitis C to that seen with other more responsive hepatitis C genotypes treated with only peginterferon and ribavirin. However, telaprevir has additional side affects such as rash and anemia that may limit its usefulness. Intriguingly, about one third of patients infected with genotype 1 hepatitis C, who have a specific variation (polymorphism) in the DNA sequence (CC) near an immune response gene (IL28B), in fact are highly responsive to 2-drug treatment with peginterferon and ribavirin. This raises the possibility that individuals who have the IL28B CC polymorphism may not need to be treated with the addition of telaprevir and could therefore be spared unnecessary side effects. Thus, the purpose of this study is to determine among genotype 1 hepatitis C patients with the IL28B CC polymorphism the success rate and side effects of 3-drug treatment compared with 2-drug treatment.

In this study, patients with genotype 1 chronic hepatitis C who have the IL28B CC polymorphism will be randomly assigned to be treated with telaprevir, peginterferon, and ribavirin or with only peginterferon with ribavirin. These medications and the procedures involved, including patient history, physical examination, and obtaining small volume blood specimens (less than 4 teaspoons) for laboratory testing, are within the scope of standard management of hepatitis C treatment. All patients will be monitored during treatment with periodic blood testing (weeks 2, 4, and every 4 weeks thereafter while on treatment, and 24 weeks after stopping treatment) and office visits (weeks 5, 12, 25, 49 while on treatment and 25 weeks after stopping treatment). The success of treatment will be judged by the presence or absence of detectable virus in blood, as measured by a sensitive diagnostic test (PCR). The data to be generated will include measurement by PCR of hepatitis C viral loads before, during, and after treatment, as well as reporting of adverse drug effects.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Vermont
• Treatments: Peginterferon alfa-2a; Ribavirin

Criteria

Inclusion Criteria:

• Age > 18 years

• Serum Hepatitis C RNA > 10,000IU/mL

• Hepatitis C virus genotype 1

• IL28B polymorphism

Exclusion Criteria:

• Previous treatment for chronic Hepatitis C

• clinical or biological evidence of acute hepatitis, including serum ALT or AST > 300U/ml

• HIV antibody positive, hepatitis b surface antigen positive or known diagnosis of other chronic liver disease

• Contraindications to PR-based treatment:

1. uncontrolled psychiatric illness

2. active substance dependency

3. Known autoimmune disorder

4. Untreated thyroid disease

5. Uncontrolled seizure disorder

6. Pregnancy, lactation or inability to maintain contraception

7. Chronic kidney disease w/ estimated GFR< 60

8. ANC<1.5/nl, Hb<12g/dl, or platelets<75/nl

• Clinical or biochemical evidence of decompensated liver disease including:

1. History of encephalopathy, ascites, or variceal bleeding OR

2. Bilirubin > 3g/dl or INR > 1.5

• Life threatening disorder with expected median survival less than 5 years

• Inability to comply with drug regimens or testing schedule required for study

• Lack of insurance coverage for any of the study medications