Hepatitis C Treatment Naive Genotype 1 Consensus Interferon Trial

This study has been completed.
Sponsor:
Collaborators:
Minneapolis Veterans Affairs Medical Center
Minnesota Veterans Research Institute
InterMune
Kadmon Pharmaceuticals
San Diego Veterans Healthcare System
Information provided by:
Minneapolis Veterans Affairs Medical Center
ClinicalTrials.gov Identifier:
NCT00211692
First received: September 13, 2005
Last updated: February 17, 2011
Last verified: September 2005
  Purpose

Data have suggested that consensus interferon (CIFN) has greater antiviral activity in vitro compared with interferon alfa-2a or alfa-2b. Several clinical studies also suggest that CIFN has greater antiviral activity in patients with genotype 1 hepatitis C infection, particularly if given as a daily injection. These data indicate that the use of a regimen of daily CIFN and ribavirin will lead to greater virologic response rates compared with pegylated interferon alfa-2b and ribavirin in patients with genotype 1 infection, with comparable adverse events. Emerging data indicate that HCV genotype 1 patients with a delayed virologic response to initial therapy may benefit from an extended duration of therapy. Therefore, the goals of this pilot study are to determine the tolerability and efficacy of daily CIFN plus ribavirin when given for 52 weeks or an extended duration of therapy. The target population will consist of "difficult-to-treat" patients, defined as having the following characteristics: genotype 1, a North American patient population, predominantly male gender, and no specific exclusions for pre-existing psychiatric or substance abuse co-morbidities.


Condition Intervention Phase
Chronic Hepatitis C
Drug: consensus interferon (Interferon Alfacon-1) and ribavirin
Drug: Consensus Interferon alfa (CIFN) and ribavirin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Randomized Pilot Study of Daily Consensus Interferon (CIFN) and Ribavirin for 52 Wks vs Extended Duration 72 Wks Based on Virologic Response for the Initial Treatment of Difficult-to-treat Patients With Chronic HCV Genotype 1

Resource links provided by NLM:


Further study details as provided by Minneapolis Veterans Affairs Medical Center:

Primary Outcome Measures:
  • The primary endpoint would be the number who achieve a sustained virologic response.

Secondary Outcome Measures:
  • Secondary endpoints are the percentage of patients who complete therapy, have significant adverse events, and the relationship of early virologic response at each 4 week period between 4 and 24 weeks and those who achieve a sustained virologic response.

Enrollment: 64
Study Start Date: July 2005
Study Completion Date: September 2009
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group A 52 weeks treatment
Daily CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given 52 weeks (group A)
Drug: consensus interferon (Interferon Alfacon-1) and ribavirin
CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B)
Other Name: interferon alfacon-1
Drug: Consensus Interferon alfa (CIFN) and ribavirin
CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B)
Other Name: interferon alfacon-1
Experimental: Group B duration based on viral response
CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for 52-72 weeks (from time of viral response +48 weeks) (group B)
Drug: Consensus Interferon alfa (CIFN) and ribavirin
CIFN (15 mcg/day SQ) and RBV (1-1.2 g/d PO) given for either 52 weeks (group A, n = 33) or 52-72 weeks (from time of viral response +48 weeks) (group B)
Other Name: interferon alfacon-1

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

1. Chronic hepatitis C. This is defined as the documentation of the presence of circulating hepatitis C virus by a positive hepatitis C PCR test and a positive HCV genotype test for genotype 1, and a liver biopsy (within the previous 5 years) that is compatible with chronic hepatitis. (Note: no requirement is made for the presence of abnormal transaminases. Patients with persistently normal transaminases are allowed if they meet the definition of chronic hepatitis C above). Liver biopsy data is required on at least 90% of enrolled patients to allow for the potential refusal of patients for the liver biopsy test. In the case of patients that have refused liver biopsies a clinical diagnosis of chronic hepatitis C is required. In the absence of a liver biopsy within five years the clinical diagnosis requires a history compatible with a chronic hepatitis C infection with the documentation of the presence of circulating hepatitis C virus by a positive hepatitis C PCR test and a positive HCV genotype test for genotype 1, and biochemical evidence of prior abnormal transaminases at two times covering a time span of at least 6 months.

2. Positive HCV RNA by PCR, Genotype 1, treatment naive 3. Age 18-65 years. 4. Patient must be able to give informed consent. 5. Eligible for interferon alfa and ribavirin-based antiviral treatment:

  1. Negative pregnancy test at entry within 48 hours of starting treatment.
  2. Reconfirmation and documentation that sexually active female patients of childbearing potential are practicing adequate contraception. A urine pregnancy test obtained at entry prior to the initiation of treatment must be negative.
  3. Reconfirmation that sexually active male subjects are practicing acceptable methods of contraception during the treatment period and for six months following the last dose of study medication.
  4. For patients with cirrhosis or stage 4 fibrosis on liver biopsy, they must have an alpha fetoprotein (AFP) value < 80 ng/mL obtained within 3 months prior to entry. Cirrhotics with an alpha fetoprotein value >30 ng/mL but <80ng/mL may be enrolled after a normal ultrasound or triphasic CT scan within the previous 3 months. Cirrhotics with alpha fetoprotein levels up to 30 ng/ml must have an ultrasound or CT scan within 6 months of enrolling that is negative for hepatocellular cancer. Patients with an AFP > 80 ng/mL may not be enrolled. Cirrhotics must have ongoing HCC screening during study.
  5. Compensated liver disease with the following laboratory results at entry:

    • Hemoglobin greater than or equal to 12 gm/dL for females and greater than or equal to 13 gm/dL for males
    • WBC greater than or equal to 2,000/mm3
    • Neutrophil count greater than or equal to 1,500/mm3
    • Platelets greater than or equal to 75,000/mm3
    • Albumin > 3.0 g/dL
    • Total bilirubin <2.0
    • Serum creatinine < 1.4 mg/dL
    • INR <1.8
    • If diabetic, must have glycosylated Hgb test that demonstrates adequate control of diabetes in the opinion of the investigator
    • TSH within normal limits (including patients with hypothyroidism controlled by thyroid hormone replacement)

Exclusion Criteria:

  1. Patient unable or unwilling to participate.
  2. Liver disease in addition to chronic hepatitis C (HBsAg positive, prior diagnosis of or known autoimmune liver disease, hemochromatosis, PBC, PSC, alpha-1 antitrypsin deficiency, Wilson's disease, etc.)
  3. Decompensated liver disease, with history of encephalopathy, variceal bleeding, or ascites or CHILD-PUGH class B or C.
  4. Baseline BDI > 19 or current suicidal or homicidal ideation. (Note: if baseline BDI is > 19 pt. will require a psychiatric evaluation and treatment; if deemed stable after this he may be considered according to site PI clinical judgment.)
  5. Current substance use disorder (Must be evaluated and demonstrate engagement and compliance with care before they will be eligible).
  6. Patients with active or uncontrolled psychiatric disease including:

    o patients who have had recent prior severe psychiatric disease, such as patients who were previously hospitalized with major depressive or bipolar or major psychotic disorder within the last 2 years, and patients who were previously hospitalized for suicide attempts within the last two years,

    • patients with prior traumatic brain injury and persistent deficits related to this, and
    • patients who have a recent (past five year) history of, or who are known to be at risk for, homicidal ideation or assaultive behavior.:
  7. Accepted and reasonable exclusion criteria for interferon alfa and ribavirin based treatments:

1) CNS trauma or active seizure disorders requiring medication. 2) Significant cardiovascular dysfunction within the past 12 months 3) Poorly controlled diabetes mellitus (in the opinion of the site PI). 4) Moderate or severe chronic pulmonary disease 5) Clinically significant immunologically mediated disease 6) Hemoglobinopathies (e.g., Thalassemia) or any other cause of hemolytic anemia.

7) Evidence of decompensated liver disease such as a history of or presence of ascites, bleeding varices, or spontaneous encephalopathy or CHILD-PUGH scores B or C.

8) Any medical condition requiring, or likely to require during the course of the study, chronic systemic administration of steroids.

9) Hypersensitivity to interferon alfa or ribavirin 10) Known anti-HIV positive 11) Clinically significant retinopathy 12) Previous solid organ transplantation 13) Any condition that, in the opinion of the investigator, will prevent the patient from being compliant with study medications or appointments.

8. Patients who develop hepatic decompensation during the course of treatment. The PT/INR, total bilirubin, albumin will be repeated at the 24 week interval to allow for a re-calculation of the CHILD-PUGH score. Patients who have developed a score of 7 or greater (CHILD-PUGH class B or greater) be considered for discontinuation of the study.

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Please refer to this study by its ClinicalTrials.gov identifier: NCT00211692

Sponsors and Collaborators
Minneapolis Veterans Affairs Medical Center
Minnesota Veterans Research Institute
InterMune
Kadmon Pharmaceuticals
San Diego Veterans Healthcare System
Investigators
Principal Investigator: Samuel B. Ho, M.D. Department of Veterans Affairs
  More Information

Publications:
Responsible Party: Samuel B. Ho, M.D., VA San Diego Healthcare System
ClinicalTrials.gov Identifier: NCT00211692     History of Changes
Other Study ID Numbers: MVRI001
Study First Received: September 13, 2005
Last Updated: February 17, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Minneapolis Veterans Affairs Medical Center:
Hepatitis C
interferon alfa
ribavirin
interferon alfacon-1
antiviral therapy

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferons
Ribavirin
Interferon-alpha
Interferon alfacon-1
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antiviral Agents
Anti-Infective Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 18, 2014