NCT00624325

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Jul 2007

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2007

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

January 7, 2008

Completed
2 months until next milestone

First Posted

Study publicly available on registry

February 27, 2008

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2010

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2010

Completed
Last Updated

March 11, 2011

Status Verified

March 1, 2011

Enrollment Period

2.9 years

First QC Date

January 7, 2008

Last Update Submit

March 10, 2011

Conditions

Chronic Hepatitis C

Keywords

genotype 1 nonresponders

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (5)

  • HCV RNA negativity at week 48 and 24 weeks after end of treatment

    48 weeks

  • Biological activity of IFN-a2b

    48 weeks

  • Pharmacokinetics by IFN-a2b levels

    48 weeks

  • HCV-specific immune responses

    48 weeks

  • Quality of life assessment using SF-36 and SCL-90 questionnaires

    48 weeks

Study Arms (3)

1

EXPERIMENTAL

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

Drug: interferon alfa-2b

2

EXPERIMENTAL

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

Drug: interferon alfa-2b

3

EXPERIMENTAL

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

Drug: interferon alfa-2b

Interventions

interferon alfa-2bDRUG

12 MU daily continuously subcutaneous

Also known as: Intron A
1

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Erasmus University Medical Center

Rotterdam, 3015 GD, Netherlands

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

Interferon alpha-2Introns

Condition Hierarchy (Ancestors)

Hepatitis CBlood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Interferon-alphaInterferon Type IInterferonsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsProteinsBiological FactorsDNA, IntergenicGenome ComponentsGenomeGenetic StructuresGenetic PhenomenaGene ComponentsGenes

Study Officials

  • R.J. de Knegt, MD, PhD

    Erasmus Medical Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

January 7, 2008

First Posted

February 27, 2008

Study Start

July 1, 2007

Primary Completion

June 1, 2010

Study Completion

December 1, 2010

Last Updated

March 11, 2011

Record last verified: 2011-03

Locations

NL(1)