Subcutaneous Continuous Infusion of Interferon Alfa-2b and Ribavirin in Hepatitis C Genotype 1 Nonresponders (SCIN-C)
Primary Purpose
Chronic Hepatitis C
Status
Completed
Phase
Phase 2
Locations
Netherlands
Study Type
Interventional
Intervention
interferon alfa-2b
interferon alfa-2b
interferon alfa-2b
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C focused on measuring genotype 1 nonresponders
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
Sites / Locations
- Erasmus University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
1
2
3
Arm Description
12 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin
9 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin
6 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
HCV RNA negativity at week 48 and 24 weeks after end of treatment
Biological activity of IFN-a2b
Pharmacokinetics by IFN-a2b levels
HCV-specific immune responses
Quality of life assessment using SF-36 and SCL-90 questionnaires
Full Information
NCT ID
NCT00624325
First Posted
January 7, 2008
Last Updated
March 10, 2011
Sponsor
Foundation for Liver Research
1. Study Identification
Unique Protocol Identification Number
NCT00624325
Brief Title
Subcutaneous Continuous Infusion of Interferon Alfa-2b and Ribavirin in Hepatitis C Genotype 1 Nonresponders
Acronym
SCIN-C
Official Title
Subcutaneous Continuous Infusion of Interferon Alfa-2b and Ribavirin in Hepatitis C Genotype 1 Nonresponders
Study Type
Interventional
2. Study Status
Record Verification Date
March 2011
Overall Recruitment Status
Completed
Study Start Date
July 2007 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
December 2010 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Foundation for Liver Research
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C
Keywords
genotype 1 nonresponders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
12 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin
Arm Title
2
Arm Type
Experimental
Arm Description
9 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin
Arm Title
3
Arm Type
Experimental
Arm Description
6 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin
Intervention Type
Drug
Intervention Name(s)
interferon alfa-2b
Other Intervention Name(s)
Intron A
Intervention Description
12 MU daily continuously subcutaneous
Intervention Type
Drug
Intervention Name(s)
interferon alfa-2b
Other Intervention Name(s)
Intron A
Intervention Description
9 MU daily continuously subcutaneous
Intervention Type
Drug
Intervention Name(s)
interferon alfa-2b
Other Intervention Name(s)
Intron A
Intervention Description
6 MU daily continuously subcutaneous
Primary Outcome Measure Information:
Title
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).
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
HCV RNA negativity at week 48 and 24 weeks after end of treatment
Time Frame
48 weeks
Title
Biological activity of IFN-a2b
Time Frame
48 weeks
Title
Pharmacokinetics by IFN-a2b levels
Time Frame
48 weeks
Title
HCV-specific immune responses
Time Frame
48 weeks
Title
Quality of life assessment using SF-36 and SCL-90 questionnaires
Time Frame
48 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
R.J. de Knegt, MD, PhD
Organizational Affiliation
Erasmus Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Erasmus University Medical Center
City
Rotterdam
ZIP/Postal Code
3015 GD
Country
Netherlands
12. IPD Sharing Statement
Learn more about this trial
Subcutaneous Continuous Infusion of Interferon Alfa-2b and Ribavirin in Hepatitis C Genotype 1 Nonresponders
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