Addition of ISIS 14803 to Therapy With Peginterferon and Ribavirin for Chronic Hepatitis C (HCV) Patients Not Responding Adequately to the Two Drugs

Sponsor

Ionis Pharmaceuticals, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT00062816

Collaborator

(none)

Enrollment

Locations

0.9

Patients Per Site

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C, Chronic	Drug: ISIS 14803, peginterferon alfa, ribavirin	Phase 1/Phase 2

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.

Study Design

Study Type:

Interventional

Primary Purpose:

Treatment

Study Start Date :

May 1, 2004

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

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