Individually Adapted Therapy Duration for the Treatment of Chronic Hepatitis C Genotype 1 Infection

FGK Clinical Research

Status and phase: Completed; Phase 4

Conditions: Hepatitis C, Chronic

Treatments: Drug: Peginterferon alfa 2b; Drug: Ribavirin

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00351403

2006-000358-38 (EudraCT Number)

INDIV-2

Details and patient eligibility

About

Patients with chronic hepatitis C genotype 1 virus infection are usually treated with Interferon alfa plus Ribavirin over 48 weeks. For some patients this might be too long, for others too short. An individually adapted therapy length from 24 to 72 weeks will be determined in dependence of the initial virus load and the time to HCV RNA negativity.

The primary objective is to compare the cumulative rate of the sustained viral response (SVR) of the patients with the individually adapted therapy duration to the SVR rates of a historic patient collective under the 48 week standard therapy.

Full description

Further objectives of this trial are:

To record the tolerance of the therapy with Peginterferon alfa-2b plus Ribavirin over 72 weeks inclusive the adverse reactions and the withdrawal rates.

To evaluate the biochemical response to the treatment (ALT values during and after the therapy) in comparison to the virological response to the treatment.

To evaluate the validity of the withdrawal rules of this trial at week 12 and 24 in comparison to the 2-log-rule and a qualitative detection of the HCV RNA at week 24 with a detection limit of 50 IU/ml.

To evaluate the impact of the HCV RNA concentration before the therapy, and the HCV kinetic during the therapy on the response to the treatment in the different groups.

To evaluate the impact of the serum concentration of Ribavirin on anaemia and the virological therapy response, as well as the dependence of the serum concentration of Ribavirin on the creatinine clearance in comparison to the body weight.

Enrollment: 390 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with a chronic HCV infection (HCV antibodies and HCV RNA positive)
• Presence of a HCV genotype 1 infection
• Presence of a compensated liver disease satisfying following hematological and biochemical minimum criteria: - Hemoglobin value >= 13 g/dl in men, >= 12 g/dl in women - Leukocytes >= 3.000/mm3 or neutrophile granulocytes > 1.500/mm3 - Thrombocytes > 80.000/mm3
• Total bilirubin in the normal range
• Albumin in the normal range
• Serum creatinine in the normal range THS in the normal range
• Exclusion of an autoimmune hepatitis
• Alpha-Fetoprotein in the normal range
• Negative HIV test
• Negativity of Hepatitis B surface antigens (Hbs-Ag)
• Normal or elevated ALT/GTP values at screening
• At known diabetes mellitus or hypertension an ophthalmologic examination must be performed
• Liver biopsy within the last 12 months must confirm the diagnoses of a chronic hepatitis
• A confirmation must be given that sexually active patients practice a save method of contraception during the therapy and 6 (women) to 7 (men) months after the therapy

Exclusion criteria

• Age < 18 years, > 70 years
• Previous treatment of hepatitis c with (Peg)Interferon alfa or (Peg)Interferon alfa/Ribavirin
• Patients with organ transplantations other than cornea or hair
• Infection with HCV genotype 2,3,4,5 or 6
• Pregnant or nursing women
• Any other reason for the liver disease than chronic hepatitis C
• Suspected hypersensitivity to Interferon, Peginterferon or Ribavirin
• Participation in a clinical trial or treatment with an investigational product 30 days before inclusion in this study
• Patients with any kind of hemoglobinopathy
• Documented liver disease in advanced state Liver cirrhosis Child B and C
• Each known and existing clinical conditions that might challenge the participation or completion of this clinical trial as depressions, psychosis, severe psychiatric diseases, suicide ideations CNS traumata or cramps which need medicamentous treatment
• Relevant cardiovascular dysfunctions in the last 6 months or patients with clinically relevant changes in the ECG
• Insufficiently adjusted diabetes mellitus
• Severe chronic lung diseases (as e.g. COPD)
• Immunologic diseases or autoimmune-diseases or any other disease which demand a longtime treatment with corticosteroids during this clinical trial
• Clinically relevant gout
• Abuse of drugs, alcohol or pharmaceuticals
• Patient with clinically relevant changes of the retina
• Missing ability or willingness to understand the purpose of this study or to give a written consent for participating in this study.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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390 participants in 2 patient groups

Individualized therapy

Experimental group

Description:

Lengh of therapy depends on time point when no HCV RNA is detectable in blood with Versant HCV Qualitative assay.

Treatment:

Drug: Peginterferon alfa 2b

Drug: Ribavirin

Historical control

Other group

Description:

48 week standard therapy

Treatment:

Drug: Peginterferon alfa 2b

Drug: Ribavirin