New Approaches to Treat Patients Who Did Not Benefit From Standard Therapy for Hepatitis C

Main Category: Liver Disease / Hepatitis
Article Date: 24 Apr 2004 - 0:00 PDT


A new study seeks to answer one of the most challenging and important questions in hepatitis C therapy today: What is the best option for patients in whom one of the most widely prescribed treatments has failed?

The study will evaluate different regimens of combination therapy in patients with hepatitis C who failed to generate a sustained virological response after treatment with Peg-Intron/Rebetol therapy.

Patients in the new study will receive Pegasys® (peginterferon alfa-2a) and CopegusÒ (ribavirin), already approved as a first-line treatment for patients with hepatitis C.

The REPEAT Trial (REtreatment with PEgasys in PATients Not Responding to Peg-Intron Therapy) is led in the U.S. by hepatologist Dr. Donald Jensen of Rush University Medical Center. The US portion of the study will enroll approximately 330 patients at 33 centers including Rush.

Hepatitis C, a blood-borne infectious disease of the liver, is transmitted through body fluids, primarily blood or blood products, and by sharing needles. Hepatitis C chronically infects an estimated 2.7 million Americans and 170 million people worldwide and is the leading cause of cirrhosis and liver cancer and the number one reason for liver transplants in the U.S.

"Although we have seen significant improvements in hepatitis C therapy over the past few years, many patients still do not respond to treatment on their first attempt," said Dr. Donald Jensen, director of Hepatology at Rush University Medical Center and lead U.S. investigator in the REPEAT trial. "We hope that this trial will provide patients a proven option with another pegylated interferon if Peg-Intron combination therapy failed to work for them."

The REPEAT Trial is an international study enrolling approximately 888 patients at 98 centers in 14 countries worldwide. Approximately 330 patients will be enrolled at the 33 participating centers in the United States.

In order to be eligible for the trial, patients must have undergone at least 12 weeks of treatment with Peg-Intron/Rebetol therapy with no response. Patients who discontinued therapy because of adverse events alone are not eligible for this study. In addition, patients must be over 18 years of age. Nationwide enrollment is currently underway for the study.

Patients will be randomized to the following treatment arms:

-- Group A: Initial high induction dose of Pegasys 360 mcg/week and Copegus 1000/1200mg daily for the first 12 weeks; additional treatment period of 60 weeks with Pegasys 180 mcg/week and Copegus 1000/1200mg daily.

-- Group B: Initial high induction dose of Pegasys 360 mcg/week and Copegus 1000/1200mg daily for the first 12 weeks; additional treatment period of 36 weeks with Pegasys 180 mcg/week and Copegus 1000/1200mg daily.

-- Group C: Treatment period of 72 weeks with Pegasys 180 mcg/week and Copegus 1000/1200mg daily.

-- Group D: Treatment period of 48 weeks with Pegasys 180 mcg/week and Copegus 1000/1200mg daily.

All patients will have a 24-week follow-up period to evaluate whether they have achieved a sustained virologic response. Sustained virological response refers to a patient's continued undetectable serum hepatitis C RNA levels 24 weeks after finishing a course of treatment.

"Although the two pegylated interferons in this study belong to the same class of medications, there are differences between the two," said Jensen. "We hope that the differences between the medications and the different dosing regimens will lead to a good alternative for patients who currently have no proven options."

Pegasys and Copegus combination therapy is marketed in the U.S. by Hoffmann-La Roche Inc. (Roche), based in Nutley, N.J. Peg-Intron and Rebetol combination therapy is marketed by Schering-Plough Corporation, based in Kenilworth, NJ.

For more information about the REPEAT trial and to locate a study site, patients can visit the "Clinical Trials" section of the American Liver Foundation website at

www.liverfoundation.org or call 1-800-GO-LIVER. Rush University Medical Center includes the 729-bed Presbyterian-St. Luke's Hospital; 79-bed Johnston R. Bowman Health Center; Rush University (Rush Medical College, College of Nursing, College of Health Sciences and the Graduate College).

Important Safety Information About Pegasys (Peginterferon alfa-2a) in Combination with Copegus

Alpha interferons, including PEGASYS (Peginterferon alfa-2a), may cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Patients should be monitored closely with periodic clinical and laboratory evaluations. Therapy should be withdrawn in patients with persistently severe or worsening signs or symptoms of these conditions. In many, but not all cases, these disorders resolve after stopping PEGASYS therapy.

Use with Ribavirin. Ribavirin, including COPEGUS®, may cause birth defects and/or death of the fetus. Extreme care must be taken to avoid pregnancy in female patients and in female partners of male patients. Ribavirin causes hemolytic anemia. The anemia associated with ribavirin therapy may result in a worsening of cardiac disease. Ribavirin is genotoxic and mutagenic and should be considered a potential carcinogen.

PEGASYS, alone or in combination with COPEGUS, is indicated for the treatment of adults with chronic hepatitis C virus infection who have compensated liver disease and have not been previously treated with interferon alpha. Patients in whom efficacy was demonstrated included patients with compensated liver disease and histological evidence of cirrhosis (Child-Pugh class A).

PEGASYS is contraindicated in patients with hypersensitivity to PEGASYS or any of its components, autoimmune hepatitis, and decompensated hepatic disease (Child-Pugh class B and C) before or during treatment with PEGASYS. PEGASYS is also contraindicated in neonates and infants because it contains benzyl alcohol. Benzyl alcohol is associated with an increased incidence of neurological and other complications in neonates and infants, which are sometimes fatal. PEGASYS and COPEGUS therapy is additionally contraindicated in patients with a hypersensitivity to COPEGUS or any of its components, in women who are pregnant, men whose female partners are pregnant, and patients with hemoglobinopathies (eg, thalassemia major, sickle-cell anemia).

COPEGUS THERAPY SHOULD NOT BE STARTED UNLESS A REPORT OF A NEGATIVE PREGNANCY TEST HAS BEEN OBTAINED IMMEDIATELY PRIOR TO INITIATION OF THERAPY. Women of childbearing potential and men must use two forms of effective contraception during treatment and during the 6 months after treatment has concluded. Routine monthly pregnancy tests must be performed during this time. If pregnancy should occur during treatment or during 6 months post-therapy, the patient must be advised of the significant teratogenic risk of COPEGUS therapy to the fetus. Physicians and patients are also strongly encouraged to report any pregnancies that do occur to Roche by calling 1-800-526-6367.

The most common adverse events reported for PEGASYS and COPEGUS combination therapy observed in clinical trials (N=451) were fatigue/asthenia (65%), headache (43%), pyrexia (41%), myalgia (40%), irritability/anxiety/nervousness (33%), insomnia (30%), alopecia (28%), neutropenia (27%), nausea/vomiting (25%), rigors (25%), anorexia (24%), injection site reaction (23%), arthralgia (22%), depression (20%), pruritus (19%) and dermatitis (16%).

Serious adverse events included neuropsychiatric disorders (suicidal ideation and suicide attempt), serious and severe bacterial infections (sepsis), bone marrow toxicity (cytopenia and rarely, aplastic anemia), cardiovascular disorders (hypertension, arrhythmias and myocardial infarction), hypersensitivity (including anaphylaxis), endocrine disorders (including thyroid disorders and diabetes mellitus), autoimmune disorders (including psoriasis and lupus), pulmonary disorders (dyspnea, pneumonia, bronchiolitis obliterans, interstitial pneumonitis and sarcoidosis), colitis (ulcerative and hemorrhagic/ischemic colitis), pancreatitis, and ophthalmologic disorders (decrease or loss of vision, retinopathy including macular edema and retinal thrombosis/hemorrhages, optic neuritis and papilledema).

From: http://www.rush.edu/webapps/MEDREL/servlet/NewsRelease?ID=547--

Rush University Medical Center's Dr. Donald Jensen Leads US Study--
Contact: John Pontarelli or Chris Martin
Phone: (312) 942-5949 or 942-7820
Email: jpontare@rush.eduor cmartin@rsh.net

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