Low-Dose Peginterferon and Ribavirin to Treat Chronic Hepatitis C in Patients Infected With HCV Genotype 2 or 3

Hepatitis C Clinical Trial

Official title:

Low Dose Peginterferon and Ribavirin Therapy for Patients With Chronic Hepatitis C Infected With Genotype 2 or 3

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00056862
• Other study ID #: 030136
• Secondary ID: 03-DK-0136
• Status: Completed
• Phase: Phase 4
• First received: March 25, 2003
• Last updated: November 13, 2013
• Start date: March 2003
• Est. completion date: June 2010

Study information

• Verified date: November 2013
• Source: National Institutes of Health Clinical Center (CC)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 58
• Est. completion date: June 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

• 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Peginterferon alfa-2a
Peginterferon alfa-2a 90 mcg/week
• Peginterferon alfa-2a
180 mcg/week
• Ribavirin
800 mg/day

Locations

Country	Name	City	State
United States	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (4)

Lauer GM, Walker BD. Hepatitis C virus infection. N Engl J Med. 2001 Jul 5;345(1):41-52. Review. — View Citation

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. — View Citation

Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, Perelson AS. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998 Oct 2;282(5386):103-7. — View Citation

Rotman Y, Borg BB, Soza A, Feld JJ, Modi AA, Loomba R, Lutchman G, Rivera E, Doo E, Ghany MG, Heller T, Neumann AU, Liang TJ, Hoofnagle JH. Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, vira — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Virological Response (Intention to Treat)	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.	6 months after stopping therapy	No
Primary	Virological Response Category (Per Protocol)	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.	6 months after therapy	No
Secondary	First Phase Decline in Logarithm of HCV RNA Level	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).	2 days	No
Secondary	Slope of Second Phase Decline in HCV Levels	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).	day 7 to day 28	No
Secondary	Time to Negativity	Time from treatment initiation to the first negative HCV RNA test during treatment	24 weeks	No