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

Chronic Hepatitis C Clinical Trial

— SCIN-C  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00624325
• Other study ID #: HCV 06-01
• Secondary ID: eudract 2006-000
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 7, 2008
• Last updated: March 10, 2011
• Start date: July 2007
• Est. completion date: December 2010

Study information

• Verified date: March 2011
• Source: Foundation for Liver Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• interferon alfa-2b
12 MU daily continuously subcutaneous
• interferon alfa-2b
9 MU daily continuously subcutaneous
• interferon alfa-2b
6 MU daily continuously subcutaneous

Locations

Country	Name	City	State
Netherlands	Erasmus University Medical Center	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Foundation for Liver Research

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of high-dose continuous subcutaneous infused IFN-a2b (serious adverse events, grade 4 NCI toxicity, percentage of patients completing treatment or reasons for dose adjustments).		48 weeks	Yes
Secondary	HCV RNA negativity at week 48 and 24 weeks after end of treatment		48 weeks	Yes
Secondary	Biological activity of IFN-a2b		48 weeks	Yes
Secondary	Pharmacokinetics by IFN-a2b levels		48 weeks	Yes
Secondary	HCV-specific immune responses		48 weeks	Yes
Secondary	Quality of life assessment using SF-36 and SCL-90 questionnaires		48 weeks	Yes