Low-Dose Peginterferon and Ribavirin to Treat Chronic Hepatitis C in Patients Infected With HCV Genotype 2 or 3
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 National Institutes of Health (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.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Low Dose Peginterferon and Ribavirin Therapy for Patients With Chronic Hepatitis C Infected With Genotype 2 or 3|
- Virological Response (Intention to Treat) [ Time Frame: 6 months after stopping therapy ] [ Designated as safety issue: No ]Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.
- Virological Response Category (Per Protocol) [ Time Frame: 6 months after therapy ] [ Designated as safety issue: No ]Virological response category. Sustained virological response (SVR) is defined as negative serum HCV RNA at least 6 months after the end of treatment. Non-response is defined as serum HCV RNA positivity on week 12 of treatment. Breakthrough/relapse is defined as HCV RNA becoming negative and subsequently positive on treatment or after treatment is stopped.
- First Phase Decline in Logarithm of HCV RNA Level [ Time Frame: 2 days ] [ Designated as safety issue: No ]The 1st phase decline is defined as the log difference between baseline HCV RNA level and the level on day 2 of treatment (see Neumann et al, Science, 1998).
- Slope of Second Phase Decline in HCV Levels [ Time Frame: day 7 to day 28 ] [ Designated as safety issue: No ]The 2nd phase slope is defined as the slope of the logarithmic viral levels from week 1 to week 4 of treatment (see Neumann et al, Science, 1998).
- Time to Negativity [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]Time from treatment initiation to the first negative HCV RNA test during treatment
|Study Start Date:||March 2003|
|Study Completion Date:||June 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Experimental: Low-dose peginterferon and standard dose ribavirin
Patients receive a lower dose of peginterferon (90 mcg per week) and standard dose of ribavirin (800 mg/d) for chronic hepatitis C, genotype 2/3, for 24 weeks.
Drug: Peginterferon alfa-2a
Other Name: PegasysDrug: Ribavirin
Other Name: Copegus
Active Comparator: Standard-dose peginterferon and ribavirin
Patients receive the standard, recommended doses of peginterferon (180 mcg per week) and ribavirin (800 mg/d) for chronic hepatitis c, genotype 2/3, for 24 weeks.
Drug: Peginterferon alfa-2a
Other Name: PegasysDrug: Ribavirin
Other Name: Copegus
Sixty patients with chronic hepatitis C infected with HCV genotype 2 or 3 will be treated using the combination of either low- or standard dose peginterferon and ribavirin for 24 weeks, with re-treatment using the standard doses and a longer duration (48 weeks) for those who do not respond to or relapse after initial low dose therapy.
Adult patients with chronic hepatitis C who have HCV genotype 2 or 3 and previously have not received anti-viral treatment will be given peginterferon alfa-2a (90 or 180 micrograms weekly by injection) and ribavirin (800 mg daily by mouth). Patients will be monitored at 2- to 4-week intervals for side effects, compliance, complete blood counts, liver biochemical tests and HCV RNA. Patients becoming HCV RNA negative by week 12 will be considered on-treatment responders, continue therapy to week 24, and be monitored thereafter for another 24 weeks. Patients who do not become HCV RNA negative by week 12 as well as patients who relapse after therapy will be retreated with 180 micrograms of peginterferon weekly and 800 mg of ribavirin for another 48 weeks.
The primary outcome will be sustained loss of HCV RNA at 24 weeks after low- or standard-dose combination therapy. Secondary outcomes include viral kinetics and side effects. Because of preliminary results in the initial 31 patients enrolled in this study, the dose of peginterferon was changed from 90 to 180 micrograms weekly for the remaining 29 patients to be enrolled, allowing for a direct comparison of efficacy, viral kinetics and side effects of standard- vs low-dose peginterferon therapy.
This study will evaluate the relative efficacy and safety of the standard versus lower doses of peginterferon with ribavirin in patients with chronic hepatitis C and HCV genotype 2 or 3.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|