The purposes of this Phase 1/2 study are to examine the safety, tolerability, and antiviral activity of ISIS 14803, when given in combination with peginterferon alfa and ribavirin, to patients who either failed to have at least a 100-fold HCV reduction at Week 12 of standard therapy or still have detectable HCV at Week 24.

Condition	Treatment or Intervention	Phase
Hepatitis C, Chronic	Drug: ISIS 14803, peginterferon alfa, ribavirin	Phase I Phase II

Previously untreated chronic hepatitis C patients undergoing therapy with peginterferon alfa and ribavirin have a very poor probability of achieving a sustained virologic response if they either do not have a 100-fold or greater reduction in their plasma HCV RNA levels at the 12th week of treatment or have detectable plasma HCV RNA at the 24th week of treatment. ISIS 14803 is an experimental antiviral medication for the treatment of chronic hepatitis C that has been given to chronic hepatitis C patients in two previous single-agent clinical trials (approximately 70 patients).

In this clinical research study, 12 weeks of ISIS 14803 treatment will be added to the peginterferon alfa and ribavirin treatment regimen of previously untreated chronic hepatitis C patients who have a very poor probability of achieving a sustained virologic response based upon either of the above two criteria. Enrolled patients must continue to be treated with peginterferon alfa and ribavirin and must begin ISIS 14803 treatment within four weeks of their HCV RNA result report date. ISIS 14803 will be given as a two-hour intravenous infusion, two times each week, for 12 weeks. Depending on their HCV response to the three-drug combination, patients may continue treatment with peginterferon alfa and ribavirin after the end of ISIS 14803 treatment. Patients will be monitored for at least eight weeks (for safety) after the end of ISIS 14803 treatment and possibly for longer (for sustained virologic response). Two dose levels of ISIS 14803 will be studied in this trial, 3 and 6 mg/kg ideal body weight.

Ages Eligible for Study:  18 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria (partial list):

• Age 18 to 65 years.
• Infection with HCV.
• Prior liver biopsy indicating chronic hepatitis.
• Received at least 12 weeks of continuous peginterferon alfa and ribavirin therapy.
• HCV infection was untreated prior to current peginterferon alfa and ribavirin regimen.
• Either less than 100-fold reduction in plasma or serum HCV RNA despite receiving 12 weeks of peginterferon alfa and ribavirin therapy or detectable HCV RNA at week 24 of therapy.
• Prothrombin time and aPTT within normal reference range.
• Serum bilirubin concentration within normal reference range.
• Give written informed consent to participate in the study.

Exclusion criteria (partial list):

• Pregnant women or nursing mothers or women of childbearing potential without adequate contraception.
• Systemic corticosteroid therapy within 3 months of screening.
• Serum ALT greater than 5 x upper limit of normal range.
• HIV or HBV infection.
• Decompensated liver disease.
• Evidence of cirrhosis.
• Severe depression with suicidal ideation requiring hospitalization within one year of screening.
• Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin.
• Any condition which, in the opinion of the Investigator, would preclude participation in or interfere with compliance.
• Alcohol or drug abuse.
• Is undergoing or has undergone treatment with another investigational drug, biologic agent or device within 30 days of screening
• History of cryoglobulinemia or vasculitis

Alabama
      Birmingham Gastroenterology Associates, Birmingham,  Alabama,  35209,  United States
Arizona
      Mayo Clinic Hospital, Phoenix,  Arizona,  85054,  United States
California
      Community Clinical Trials, Orange,  California,  92868,  United States
Colorado
      The Lynn Institute of the Rockies, Colorado Springs,  Colorado,  80909,  United States
      Western States Clinical Research, Inc., Wheat Ridge,  Colorado,  80033,  United States
Florida
      Miami Research Associates, Inc., Miami,  Florida,  33173,  United States
      University of Florida, Jacksonville,  Florida,  32209,  United States
Idaho
      Idaho Gastroenterology Assoc., Boise,  Idaho,  83702,  United States
Louisiana
      IMG Healthcare, LLC, New Orleans,  Louisiana,  70127,  United States
Massachusetts
      Beth Israel Deconess Medical Center, Boston,  Massachusetts,  02215,  United States
      FutureCare Studies, Springfield,  Massachusetts,  01107,  United States
Michigan
      William Beaumont Hospital, Royal Oak,  Michigan,  48073,  United States
Missouri
      Saint Louis University, St. Louis,  Missouri,  63110,  United States
New York
      Rochester Institute for Digestive Diseases and Sciences, Inc., Rochester,  New York,  14607,  United States
      Cornell Medical Center, New York,  New York,  10021,  United States
North Carolina
      Duke Clinical Research Institute, Durham,  North Carolina,  27705,  United States
Ohio
      Consultants for Clinical Research, Cincinnati,  Ohio,  45219,  United States
Pennsylvania
      Blair Gastroenterology Associates, Altoona,  Pennsylvania,  16602,  United States
Tennessee
      Nashville Medical Research Institute, Nashville,  Tennessee,  37205,  United States
      Memphis Gastroenterology Group, Memphis,  Tennessee,  38120,  United States
      Gastroenterology Center of the MidSouth, P.C., Germantown,  Tennessee,  38138,  United States
Texas
      Baylor College of Medicine-VAMC, Houston,  Texas,  77030,  United States
Virginia
      McGuire VAMC, Richmond,  Virginia,  23249,  United States
Washington
      Spokane Digestive Disease Center, Spokane,  Washington,  99207,  United States
      Northwest Gastroenterolgy Assoc., Bellevue,  Washington,  98004,  United States

Study ID Numbers:  ISIS 14803-CS3
Record last reviewed:  September 2004
Record first received:  June 16, 2003
ClinicalTrials.gov Identifier:  NCT00062816
Health Authority: United States: Food and Drug Administration
ClinicalTrials.gov processed this record on 2004-10-25