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

This study has been completed.
Sponsor:
Information provided by:
Foundation for Liver Research
ClinicalTrials.gov Identifier:
NCT00624325
First received: January 7, 2008
Last updated: March 10, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Chronic Hepatitis C
Drug: interferon alfa-2b
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Subcutaneous Continuous Infusion of Interferon Alfa-2b and Ribavirin in Hepatitis C Genotype 1 Nonresponders

Resource links provided by NLM:


Further study details as provided by Foundation for Liver Research:

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). [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • HCV RNA negativity at week 48 and 24 weeks after end of treatment [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Biological activity of IFN-a2b [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Pharmacokinetics by IFN-a2b levels [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • HCV-specific immune responses [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Quality of life assessment using SF-36 and SCL-90 questionnaires [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: July 2007
Study Completion Date: December 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
12 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin
Drug: interferon alfa-2b
12 MU daily continuously subcutaneous
Other Name: Intron A
Experimental: 2
9 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin
Drug: interferon alfa-2b
9 MU daily continuously subcutaneous
Other Name: Intron A
Experimental: 3
6 MU interferon alfa-2b daily continuously subcutaneous in combination with 15 mg/kg/day ribavirin
Drug: interferon alfa-2b
6 MU daily continuously subcutaneous
Other Name: Intron A

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00624325

Locations
Netherlands
Erasmus University Medical Center
Rotterdam, Netherlands, 3015 GD
Sponsors and Collaborators
Foundation for Liver Research
Investigators
Principal Investigator: R.J. de Knegt, MD, PhD Erasmus University Medical Center Rotterdam
  More Information

No publications provided

Responsible Party: R.J. de Knegt, Erasmus Medical Center Rotterdam
ClinicalTrials.gov Identifier: NCT00624325     History of Changes
Other Study ID Numbers: HCV 06-01, eudract 2006-000592-15
Study First Received: January 7, 2008
Last Updated: March 10, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Foundation for Liver Research:
genotype 1 nonresponders

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Interferon Alfa-2a
Interferon Alfa-2b
Interferons
Ribavirin
Reaferon
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 24, 2014