Peginterferon Alfa-2a and Ribavirin for Genotype 2 Chronic Hepatitis C: Duration and Ribavirin Dose Stratified by RVR - Full Text View

Sponsors and Collaborators:	National Taiwan University Hospital National Science Council, Taiwan Department of Health, Taiwan
Information provided by:	National Taiwan University Hospital
ClinicalTrials.gov Identifier:	NCT00532701

Purpose

Treatment with peginterferon plus daily low dose (800 mg) or weight-based ribavirin (800-1400 mg) for 24 to 48 weeks has achieved 70-93% sustained virologic response (SVR) rates in patients with genotype 2 or 3 chronic hepatitis C (CHC). Recently, a large randomized study has shown that patients with genotype 2 or 3 CHC have comparable SVR rates for those who received peginterferon for 24 or 48 weeks, and who received daily low dose (800 mg) or standard dose (1000-1200 mg) ribavirin. Therefore, the currently recommended treatment for these patients is 24 weeks of peginterferon plus low dose ribavirin. Because of the high response rates, several studies have shown that when these patients had rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV) ribonucleic acid (RNA) levels, at week 4 of peginterferon plus weight-based ribavirin, 12-16 weeks of treatment could have 82-94% SVR rates. However, treatment with peginterferon plus low dose ribavirin for 24 weeks showed significantly higher SVR rates than that for 16 weeks (85% versus 79%) in these patients who achieved RVR. While studies showed concordant results in SVR rates for patients with genotype 3 CHC who received peginterferon plus low dose or weight-based ribavirin for 16 or 24 weeks, the SVR rates stratified by RVR showed great differences in patients with genotype 2 CHC who received such treatment. Currently, there are no studies on the direct comparison of low dose versus weight-based ribavirin, and of 16 to 24 weeks of treatment stratified by RVR for patients with genotype 2 CHC. The investigators aimed to conduct a randomized trial to determine the optimal ribavirin dose and treatment duration of peginterferon plus ribavirin for patients with genotype 2 CHC based on RVR studies.

Condition	Intervention	Phase
Chronic Hepatitis C	Drug: Pegylated interferon alfa-2a + ribavirin	Phase IV

MedlinePlus related topics: Hepatitis Hepatitis C

Drug Information available for: Ribavirin Interferon alfa-2a Peginterferon Alfa-2a Interferon alfa-n1 Interferons

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Dose Comparison, Parallel Assignment, Safety/Efficacy Study
Official Title:	Peginterferon Alfa-2a Plus Ribavirin in Patients With Genotype 2 Chronic Hepatitis C: A Randomized Study of Treatment Duration and Ribavirin Dose Stratified by Rapid Virologic Response

Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:

Sustained virologic response (SVR) [ Time Frame: 1.5 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Histologic response (HR) [ Time Frame: 1.5 year ] [ Designated as safety issue: Yes ]
Biochemical response (BR) [ Time Frame: 1.5 ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	700
Study Start Date:	June 2006
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Weight-based ribavirin (1000-1200 mg/day) from weeks 1-16 in patients with RVR	Drug: Pegylated interferon alfa-2a + ribavirin Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 1-4 Rapid virologic response (RVR) at week 4 of therapy: achieved Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 5-16
2: Active Comparator Weight-based ribavirin (1000-1200 mg/day) from weeks 1-4, and then low dose ribavirin (800 mg/day) from weeks 5-16 in patients with RVR	Drug: Pegylated interferon alfa-2a + ribavirin Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 1-4 Rapid virologic response (RVR) at week 4 of therapy: achieved Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 800 mg/day from weeks 5-16
3: Active Comparator Weight-based ribavirin (1000-1200 mg/day) from weeks 1-24 in patients without RVR	Drug: Pegylated interferon alfa-2a + ribavirin Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 1-4 Rapid virologic response (RVR) at week 4 of therapy: not achieved Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day from weeks 5-24
4: Active Comparator Weight-based ribavirin (1000-1200 mg/day) from weeks 1-48 in patients without RVR	Drug: Pegylated interferon alfa-2a + ribavirin Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day (< 75 kg, 1000 mg/day; >= 75 kg, 1200 mg/day) from weeks 1-4 Rapid virologic response (RVR) at week 4 of therapy: not achieved Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 1000-1200 mg/day from weeks 5-48
5: Active Comparator Low dose ribavirin (800 mg/day) from weeks 1-24 in patients with or without RVR	Drug: Pegylated interferon alfa-2a + ribavirin Peginterferon alfa-2a (Pegasys, F. Hoffman-LaRoche) 180 ug/week plus ribavirin (Copegus, Hoffman-LaRoche) 800 mg/day from weeks 1-24 Rapid virologic response (RVR) at week 4 of therapy: both achieved and not achieved

Detailed Description:

Treatment with peginterferon plus daily low dose (800 mg) or weight-based ribavirin (800-1400 mg) for 24 to 48 weeks has achieved 70-93% sustained virologic response (SVR) rates in patients with genotype 2 or 3 chronic hepatitis C (CHC). Recently, a large randomized study has shown that patients with genotype 2 or 3 CHC have comparable SVR rates for those who received peginterferon for 24 or 48 weeks, and who received daily low dose (800 mg) or standard dose (1000-1200 mg) ribavirin. Therefore, the currently recommended treatment for these patients is 24 weeks of peginterferon plus low dose ribavirin. Because of the high response rates, several studies have shown that when these patients had rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV) RNA levels, at week 4 of peginterferon plus weight-based ribavirin, 12-16 weeks of treatment could have 82-94% SVR rates. However, treatment with peginterferon plus low dose ribavirin for 24 weeks showed significantly higher SVR rates than that for 16 weeks (85% vs.

79%) in these patients who achieved RVR. While studies showed concordant results in SVR rates for patients with genotype 3 CHC who received peginterferon plus low dose or weight-based ribavirin for 16 or 24 weeks, the SVR rates stratified by RVR showed great differences in patients with genotype 2 CHC who received such treatment. Currently, there are no studies on the direct comparison of low dose versus weight-based ribavirin, and of 16 to 24 weeks of treatment stratified by RVR for patients with genotype 2 CHC. We aimed to conduct a randomized trial to determine the optimal ribavirin dose and treatment duration of peginterferon plus ribavirin for patients with genotype 2 CHC based on RVR studies.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Treatment naïve
Age older than 18 years old
Anti-HCV (Abbott HCV EIA 2.0, Abbott Diagnostic, Chicago, IL) positive > 6 months
Detectable serum quantitative HCV-RNA (Cobas Taqman HCV Monitor v2.0, Roche Diagnostics) with dynamic range 25 ~ 391000000 IU/ml
HCV genotype 2 (Inno-LiPA HCV II, Innogenetics, Ghent, Belgium)
Serum alanine aminotransferase levels above the upper limit of normal with 6 months of enrollment
A liver biopsy consistent with the diagnosis of chronic hepatitis C

Exclusion Criteria:

Anemia (hemoglobin < 13 grams per deciliter for men and < 12 grams per deciliter for women)
Neutropenia (neutrophil count < 1,500 per cubic milliliter)
Thrombocytopenia (platelets < 90,000 per cubic milliliter)
Co-infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)
Chronic alcohol abuse (daily consumption > 20 grams per day)
Decompensated liver disease (Child-Pugh class B or C)
Serum creatinine level more than 1.5 times the upper limit of normal
Autoimmune liver disease
Neoplastic disease
An organ transplant
Immunosuppressive therapy
Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
Evidence of drug abuse
Unwilling to use contraception
Unwilling to sign informed consent

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00532701

Contacts

Contact: Chen-Hua Liu, MD	+886-2-23123456 ext 3572	jacque_liu@mail2000.com.tw
Contact: Jia-Horng Kao, MD, PhD	+886-2-23123456 ext 7307	kaojh@ntu.edu.tw

Locations

Taiwan
National Taiwan University Hospital	Recruiting
Taipei, Taiwan, 100
Principal Investigator: Chen-Hua Liu, MD
Principal Investigator: Jia-Horng Kao, MD, PhD
Principal Investigator: Ding-Shinn Chen, MD
Principal Investigator: Ming-Yang Lai, MD, PhD
Principal Investigator: Pei-Jer Chen, MD, PhD
Principal Investigator: Chun-Jen Liu, MD,PhD
National Taiwan University Hospital, Yun-Lin Branch	Recruiting
Douliou, Taiwan
Principal Investigator: Shih-Jer Hsu, MD
Far Eastern Memorial Hospital	Recruiting
Taipei, Taiwan
Principal Investigator: Cheng-Chao Liang, MD
Ren-Ai Branch, Taipei Municipal Hospital	Recruiting
Taipei, Taiwan
Principal Investigator: Chih-Lin Lin, MD
Paochien Hospital	Recruiting
Pingtung, Taiwan
Contact: Chang-Fu Chiu, MD
Principal Investigator: Chang-Fu Chiu, MD
Taichung Veterans General Hospital	Recruiting
Taichung, Taiwan
Principal Investigator: Sheng-Shun Yang, MD
Kaohsiung Medical University	Recruiting
Kaohsiung, Taiwan
Contact: Ming-Lung Yu, MD, PhD
Principal Investigator: Ming-Lung Yu, MD, PhD
Principal Investigator: Wan-Long Chuang, MD, PhD
Kaohsiung Municipal Hsiao-Kang Hospital	Recruiting
Kaohsiung, Taiwan
Contact: Chia-Yen Dai, MD, Ms
Principal Investigator: Chia-Yen Dai, MD, Ms
Principal Investigator: Jee-Fu Huang, MD
Buddhist Xindian Tzu Chi General Hospital	Recruiting
Taipei, Taiwan
Principal Investigator: Ching-Sheng Hsu, MD
Principal Investigator: Chia-Chi Wang, MD
Principal Investigator: Tai-Chung Tseng, MD

Sponsors and Collaborators

National Taiwan University Hospital

National Science Council, Taiwan

Department of Health, Taiwan

Investigators

Principal Investigator:	Jia-Horng Kao, MD, PhD	National Taiwan University Hospital
Principal Investigator:	Ding-Shinn Chen, MD	National Taiwan University Hospital
Principal Investigator:	Ming-Yang Lai, MD, PhD	National Taiwan University Hospital
Principal Investigator:	Pei-Jer Chen, MD, PhD	National Taiwan University Hospital
Principal Investigator:	Chun-Jen Liu, MD, PhD	National Taiwan University Hospital
Principal Investigator:	Chen-Hua Liu, MD	National Taiwan University Hospital
Principal Investigator:	Shih-Jer Hsu, MD	National Taiwan University Hospital, Yun-Lin Branch
Principal Investigator:	Chih-Lin Lin, MD	Taipei City Hospital, Ren-Ai Branch
Principal Investigator:	Cheng-Chao Liang, MD	Far Eastern Memorial Hospital
Principal Investigator:	Ching-Sheng Hsu, MD	Buddhist Xindian Tzu Chi General Hospital
Principal Investigator:	Sheng-Shun Yang, MD	Taichung Veterans General Hospital
Principal Investigator:	Chia-Chi Wang, MD	Buddhist Xindian Tzu Chi General Hospital
Principal Investigator:	Tai-Chung Tseng, MD	Buddhist Xindian Tzu Chi General Hospital
Principal Investigator:	Ming-Lung Yu, MD, PhD	Kaohsiung Medical University
Principal Investigator:	Wan-Long Chuang, MD, PhD	Kaohsiung Medical University
Principal Investigator:	Chia-Yen Dai, MD, Ms	Kaohsiung Municipal Hsiao-Kang Hospital
Principal Investigator:	Jee-Fu Huang, MD	Kaohsiung Municipal Hsiao-Kang Hospital
Principal Investigator:	Chang-Fu Chiu, MD	Paochien Hospital

More Information

Publications:

Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65.

Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, Haussinger D, Diago M, Carosi G, Dhumeaux D, Craxi A, Lin A, Hoffman J, Yu J. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002 Sep 26;347(13):975-82.

Hadziyannis SJ, Sette H Jr, Morgan TR, Balan V, Diago M, Marcellin P, Ramadori G, Bodenheimer H Jr, Bernstein D, Rizzetto M, Zeuzem S, Pockros PJ, Lin A, Ackrill AM; PEGASYS International Study Group. Peginterferon-alpha2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004 Mar 2;140(5):346-55.

Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, Sarrazin C, Harvey J, Brass C, Albrecht J. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients infected with HCV genotypes 2 or 3. J Hepatol. 2004 Jun;40(6):993-9. Erratum in: J Hepatol. 2005 Mar;42(3):434.

Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Sola R, Shafran SD, Barange K, Lin A, Soman A, Zeuzem S; ACCELERATE Investigators. Peginterferon alfa-2a and ribavirin for 16 or 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2007 Jul 12;357(2):124-34.

Strader DB, Wright T, Thomas DL, Seeff LB; American Association for the Study of Liver Diseases. Diagnosis, management, and treatment of hepatitis C. Hepatology. 2004 Apr;39(4):1147-71. No abstract available. Erratum in: Hepatology. 2004 Jul;40(1):269.

Dalgard O, Bjoro K, Hellum KB, Myrvang B, Ritland S, Skaug K, Raknerud N, Bell H. Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology. 2004 Dec;40(6):1260-5.

von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, Haussinger D, Herrmann E, Zeuzem S. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology. 2005 Aug;129(2):522-7.

Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, Vinelli F, Scotto G, Bacca D, Annese M, Romano M, Zechini F, Sogari F, Spirito F, Andriulli A. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med. 2005 Jun 23;352(25):2609-17.

Yu ML, Dai CY, Huang JF, Hou NJ, Lee LP, Hsieh MY, Chiu CF, Lin ZY, Chen SC, Hsieh MY, Wang LY, Chang WY, Chuang WL. A randomised study of peginterferon and ribavirin for 16 versus 24 weeks in patients with genotype 2 chronic hepatitis C. Gut. 2007 Apr;56(4):553-9. Epub 2006 Sep 6.

Responsible Party:	National Taiwan University Hospital ( National Taiwan University Hospital )
Study ID Numbers:	200709014M
Study First Received:	September 18, 2007
Last Updated:	December 21, 2008
ClinicalTrials.gov Identifier:	NCT00532701 History of Changes
Health Authority:	Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:

Chronic hepatitis C
Genotype
Interferon

Ribavirin
Genotype 2
Peginterferon

Study placed in the following topic categories:

Antimetabolites
Interferon-alpha
Interferon Type I, Recombinant
Liver Diseases
Immunologic Factors
Hepatitis, Chronic
Ribavirin
Interferons
Hepatitis, Viral, Human

Angiogenesis Inhibitors
Antiviral Agents
Hepatitis
Virus Diseases
Digestive System Diseases
Peginterferon alfa-2a
Hepatitis C
Interferon Alfa-2a
Hepatitis C, Chronic

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Interferon Type I, Recombinant
Liver Diseases
Molecular Mechanisms of Pharmacological Action
Flaviviridae Infections
Hepatitis, Chronic
Immunologic Factors
Antineoplastic Agents
Ribavirin
Physiological Effects of Drugs
Hepatitis, Viral, Human
Therapeutic Uses
Growth Inhibitors
Hepatitis C

Angiogenesis Modulating Agents
Interferon-alpha
RNA Virus Infections
Growth Substances
Interferons
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Virus Diseases
Hepatitis
Digestive System Diseases
Peginterferon alfa-2a
Interferon Alfa-2a
Hepatitis C, Chronic

ClinicalTrials.gov processed this record on May 07, 2009