Subcutaneous Continuous Infusion of Interferon Alfa-2b and Ribavirin in Hepatitis C Genotype 1 Nonresponders

NCT ID: NCT00624325

Last Updated: 2011-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-07-31
• Study Completion Date: 2010-12-31

Brief Summary

For chronic hepatitis C patients unresponsive to previous (PEG-)IFN/RBV combination therapy we propose continuous subcutaneous administration of high-dose IFN-a2b (Intron A®) for 48 weeks in combination with 15 mg/kg/day RBV (Rebetol®) and optimal management of side effects in order to maintain the highest possible dosages of both IFN-a2b and RBV for 48 weeks. We expect improved tolerability with continuous subcutaneous pump delivery of IFN-a2b compared to thrice weekly or daily subcutaneous injection of IFN-a2b, and increased antiviral activity and biologic potency due to sustained and higher levels of a fully potent interferon protein.

Conditions

Chronic Hepatitis C

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

12 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin

Group Type: EXPERIMENTAL

interferon alfa-2b

Intervention Type: DRUG

12 MU daily continuously subcutaneous

2

9 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin

Group Type: EXPERIMENTAL

interferon alfa-2b

Intervention Type: DRUG

9 MU daily continuously subcutaneous

3

6 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin

Group Type: EXPERIMENTAL

interferon alfa-2b

Intervention Type: DRUG

6 MU daily continuously subcutaneous

Interventions

interferon alfa-2b

12 MU daily continuously subcutaneous

Intervention Type: DRUG

interferon alfa-2b

9 MU daily continuously subcutaneous

Intervention Type: DRUG

interferon alfa-2b

6 MU daily continuously subcutaneous

Intervention Type: DRUG

Other Intervention Names

Intron A; Intron A; Intron A

Eligibility Criteria

Inclusion Criteria

• Hepatitis C genotype 1 unresponsive to (peg)interferon /ribavirin therapy
• In the past, peginterferon or conventional interferon plus ribavirin combination therapy for at least 12 weeks and less than 2-log HCV RNA decrease at week 12, HCV RNA positivity at week 24, breakthrough during therapy or relapse after therapy
• At least 12 weeks between end of (peg)interferon/ribavirin therapy and start of high-dose IFN/ribavirin therapy
• Persistent indication for antiviral therapy such as persistently elevated serum ALT or histological evidence of continuing or progressive fibrosis
• Age 18-60 years

Exclusion Criteria

• Signs of progressive liver disease since end of previous therapy, beyond generally accepted criteria for HCV antiviral therapy:

• serum bilirubin >35 μmol/l, albumin <36 g/l, prothrombin time >4 sec prolonged or platelets <100,000/mm3
• decompensated cirrhosis (defined as jaundice in the presence of cirrhosis, ascites, gastric bleeding, esophageal varices or encephalopathy)
• Hepatic imaging (US, CT or MRI) with the evidence of hepatocellular carcinoma (hepatic imaging should be performed within 3 months prior to screening) or an alpha fetoprotein >50 ng/ml
• Other acquired or inherited causes of liver disease that could explain liver disease activity
• Co-infection with hepatitis B virus or human immunodeficiency virus (HIV)
• Other significant medical illness that might interfere with this study: significant cardiovascular, pulmonary or renal dysfunction, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes (e.g.: HIV positivity, steroid therapy, organ transplants other than cornea and hair transplant)
• History of a severe seizure disorder or current anticonvulsant use
• History of thyroid disease poorly controlled on prescribed medications
• Contra-indications for IFN and/or ribavirin:

• Severe psychiatric disorder, such as major psychoses, suicidal ideation, suicidal attempt and/or manifest depression during previous (peg)interferon therapy. Severe depression would include the following: (a) subjects who have been hospitalized for depression, (b) subjects who have received electroconvulsive therapy for depression, or (c) subjects whose depression has resulted in a prolonged absence of work and/or significant disruption of daily functions. Subjects with a history of mild depression may be considered for entry into the protocol provided that a pretreatment assessment of the subject's mental status supports that the subject is clinically stable and that there is ongoing evaluation of the patient's mental status during the study
• Reactivation of immunological disorders during previous therapy
• Visual symptoms related to retinal abnormalities
• Pregnancy, breast-feeding or inadequate contraception
• Thalassemia, spherocytosis
• Substance abuse, such as alcohol (³80 gm/day) and I.V. drugs. If the subject has a history of substance abuse, to be considered for inclusion into the protocol, the subject must have abstained from using the abused substance for at least 2 years
• Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Foundation for Liver Research

OTHER

Sponsor Role: lead

Responsible Party

Erasmus Medical Center Rotterdam

Principal Investigators

R.J. de Knegt, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Erasmus Medical Center

Locations

Erasmus University Medical Center

Rotterdam, , Netherlands

Countries

Netherlands

Other Identifiers

eudract 2006-000592-15

Identifier Type: -

Identifier Source: secondary_id

HCV 06-01

Identifier Type: -

Identifier Source: org_study_id