Clinical trial NCT00062816: Addition of ISIS 14803 to Therapy With Peginterferon and Ribavirin for Chronic Hepatitis C (HCV) Patients Not Responding Adequately to the Two Drugs
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis
Chronic
Lead sponsor: Ionis Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2003-06-18
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Birmingham Gastroenterology Associates
state: Alabama
city: Phoenix
country: United States
facility: Mayo Clinic Hospital
state: Arizona
city: Orange
country: United States
facility: Community Clinical Trials
state: California
city: Colorado Springs
country: United States
facility: The Lynn Institute of the Rockies
state: Colorado
city: Wheat Ridge
country: United States
facility: Western States Clinical Research, Inc.
state: Colorado
city: Jacksonville
country: United States
facility: University of Florida
state: Florida
city: Miami
country: United States
facility: Miami Research Associates, Inc.
state: Florida
city: Boise
country: United States
facility: Idaho Gastroenterology Assoc.
state: Idaho
city: New Orleans
country: United States
facility: IMG Healthcare, LLC
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deconess Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: FutureCare Studies
state: Massachusetts
city: Royal Oak
country: United States
facility: William Beaumont Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Saint Louis University
state: Missouri
city: New York
country: United States
facility: Cornell Medical Center
state: New York
city: Rochester
country: United States
facility: Rochester Institute for Digestive Diseases and Sciences, Inc.
state: New York
city: Durham
country: United States
facility: Duke Clinical Research Institute
state: North Carolina
city: Cincinnati
country: United States
facility: Consultants for Clinical Research
state: Ohio
city: Altoona
country: United States
facility: Blair Gastroenterology Associates
state: Pennsylvania
city: Germantown
country: United States
facility: Gastroenterology Center of the MidSouth, P.C.
state: Tennessee
city: Memphis
country: United States
facility: Memphis Gastroenterology Group
state: Tennessee
city: Nashville
country: United States
facility: Nashville Medical Research Institute
state: Tennessee
city: Houston
country: United States
facility: Baylor College of Medicine-VAMC
state: Texas
city: Richmond
country: United States
facility: McGuire VAMC
state: Virginia
city: Bellevue
country: United States
facility: Northwest Gastroenterolgy Assoc.
state: Washington
city: Spokane
country: United States
facility: Spokane Digestive Disease Center
state: Washington
Study officials:
References: