Title: Low Dose Peginterferon and Ribavirin Therapy for Patients
with Chronic Hepatitis C Infected with Genotype 2 or 3
Number: 03-DK-0136
Summary: This study will examine the effectiveness of low-dose
peginterferon and ribavirin therapy for certain patients with
chronic hepatitis C-a liver disease that, in some patients, can
progress to cirrhosis of the liver, liver cancer, and liver failure.
This disease is caused by the hepatitis C virus (HCV). There are six
major strains, or genotypes, of HCV. Patients infected with
genotypes 2 and 3 respond better and more quickly to the standard
treatment for this disease-high-dose peginterferon and ribavirin for
24 to 48 weeks-than do patients with other genotypes. Although the
side effects of these medications are more severe at higher doses,
patients with all genotypes, including genotypes 2 and 3, currently
receive the same standard treatment. This study will examine whether
patients infected with HCV genotypes 2 and 3 will respond equally
well, and with fewer side effects, to lower doses of peginterferon
and ribavirin given for a shorter period of time.

Patients 18 years of age and older with chronic hepatitis C genotype
2 or 3 may be eligible for this study. Each candidate will be
screened with a medical history, physical examination, blood tests,
and liver ultrasound. Patients who have not had a chest x-ray or
electrocardiogram within a year of entering the study will have
those tests as well. Additional tests, such as eye examination,
hearing test, stress test, or others, will be done if deemed
necessary because of the individual's particular medical condition
or risk factors for side effects of therapy.

Participants will be admitted to the NIH Clinical Center for 1 day
for supervised administration of the first doses of peginterferon
and ribavirin and 24-hour observation. The treatment regimen
consists of two capsules of ribavirin twice a day every day and an
injection of peginterferon under the skin once a week. Patients will
return to the clinic at 2, 4, 8, 12, 16, 20 and 24 weeks after the
first dose of therapy for a brief medical history and physical
examination, blood test, and check on hepatitis symptoms and
treatment side effects. Women capable of becoming pregnant will also
have a pregnancy test at each visit.

Patients will be tested for HCV levels after 12 weeks of therapy.
Those who are negative for the virus at that time will continue
therapy for another 12 weeks to insure that the response lasts. They
will be monitored during that time and re-tested for the virus at
the end of that period. Patients who do not respond to treatment
after 12 weeks will stop low-dose therapy and be offered the higher-
dose standard treatment for 48 weeks. Patients who responded after
12 weeks and completed 24 weeks of therapy but subsequently became
positive after stopping treatment will also be offered standard high-
dose treatment for the full 48-week regimen. Patients on high-dose
therapy will return to the clinic every 4 weeks during the 48-week
course for evaluation and blood tests. Patients who remain positive
for HCV after 24 weeks of high-dose therapy will stop treatment, as
a response is unlikely to occur beyond that time.

After treatment, patients will return to the clinic at 4- to 8-week
intervals for evaluations until 6 months. At 6 months, they will
have a series of blood and urine tests and ultrasound of the liver.


Sponsoring Institute:
National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): None

Eligibility Criteria:
INCLUSION CRITERIA:

Age above 18 years, male or female.


Presence of anti-HCV in serum.


Positive HCV RNA determination in serum.


HCV genotype 2 or 3 as determined by Inno LiPa assay or by direct
sequencing. Patients with mixed genotypes will not be eligible if
they have genotypes other than 2 or 3.


Written informed consent.


EXCLUSION CRITERIA:


Previous treatment with interferon alpha or peginterferon.


Decompensated liver disease, as marked by bilirubin greater than 4
mg/dL, albumin less than 3.0 g/dL, prothrombin time greater than 2
sec prolonged, or history of bleeding esophageal varices, ascites or
hepatic encephalopathy.


Patients with ALT levels greater than 1000 U/L (greater than 25
times ULN) will not be enrolled but may be followed until three
determinations are below this level.


Pregnancy or, in women of child-bearing potential or in spouses of
such women, inability to practice adequate contraception, defined as
vasectomy in men, tubal ligation in women, or use of condoms and
spermicidal, or birth control pills, or an intrauterine device.


Significant systemic or major illnesses other than liver disease,
including congestive heart failure, renal failure (creatinine
clearance less than 50 ml/min), organ transplantation, serious
psychiatric disease not controlled by psychotropic agents, and
angina pectoris.


Evidence of coronary artery disease or cerebral vascular disease,
including abnormalities on exercise stress testing in patients with
defined risk factors who will be screened for evidence of underlying
coronary artery disease.


Pre-existing, severe bone marrow compromise; anemia (hematocrit less
than 30%), neutropenia (less than 1000 neutrophils/microliter) or
thrombocytopenia (less than 70,000 cells/microliter).


History of hemolytic anemia.


Evidence of another form of liver disease in addition to hepatitis C
(for example hepatitis B, autoimmune liver disease, Wilson's
disease, alcoholic liver disease).


Active substance abuse, such as alcohol, inhaled or injection drugs
within the previous six months.


Evidence of hepatocellular carcinoma: either alfa-fetoprotein (AFP)
levels greater than 50 ng/ml (normal less than 9 ng/ml) and/or
ultrasound (or other imaging study) demonstrating a mass suggestive
of liver cancer.


Clinical gout.


HIV infection.


Quiescent or active, serious autoimmune disease such as lupus
erythematosus, ulcerative colitis, Crohn's disease or rheumatoid
arthritis that in the opinion of the investigators might be
exacerbated by therapy with alfa interferon.


The use of immunosuppressive medications, including corticosteroids
in doses of 10 mg of prednisone or its equivalent and higher.


Special Instructions: Currently Not Provided
Keywords:
Hepatitis C Virus
Antiviral Agents
Hemolysis
Neutropenia
Cirrhosis
Hemolytic Anemia
Viral Hepatitis
Ribavirin
Alfa Interferon
Pegylated Interferon
Recruitment Keyword(s):
Hepatitis C
HCV
Condition(s):
Hepatitis C
Investigational Drug(s):
Peginterferon alfa-2a and ribavirin for chronic hepatitis C
Investigational Device(s):
None
Intervention(s):
None
Supporting Site:
N/A

Contact(s):
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@...

Citation(s):
Liang TJ, Rehermann B, Seeff LB, Hoofnagle JH. Pathogenesis, natural
history, treatment, and prevention of hepatitis C. Ann Intern Med.
2000 Feb 15;132(4):296-305. Review.

Major ME, Feinstone SM. Related Articles, Links The molecular
virology of hepatitis C. Hepatology. 1997 Jun;25(6):1527-38. Review.
No abstract available.

Lauer GM, Walker BD. Related Articles, Hepatitis C virus infection.
N Engl J Med. 2001 Jul 5;345(1):41-52. Review. No abstract
available.




If you have:

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Recruitment and Public Liaison Office, CC.
Technical questions regarding the Clinical Center web site, please
contact the Department of Networks and Applications, CC.