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Study to Assess the Efficacy of 12 Versus 24 Weeks of Extended Treatment in HCV-Genotype 2/3 Patients

Information source: HepNet Study House, German Liverfoundation
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Hepatitis C, Chronic

Intervention: pegylated interferon alpha-2b (Drug); Ribavirin (Drug); pegylated Interferon alpha-2b (Drug); Ribavirin (Drug)

Phase: Phase 4

Status: Terminated

Sponsored by: HepNet Study House, German Liverfoundation

Official(s) and/or principal investigator(s):
Michael P. Manns, Prof. Dr., Study Director, Affiliation: Hannover Medical School

Summary

In this study we intend to treat patients with chronic hepatitis C of genotype 2 or 3 having characteristics associated with poor treatment response for additional 12 or 24 weeks beyond the standard treatment of PEG-IFN alpha-2b plus ribavirin. The objective of this study is to compare the efficacy of a treatment extension of 12 versus 24 weeks in patients with HCV-genotypes 2 and 3 who are treated with 1. 5 Ág/kg PEG-IFN alpha-2b and 800-1400 mg ribavirin (standard dose) for 24 weeks (standard duration) and who are not HCV-RNA negative (< 15 IU/ml) after 4 weeks of standard treatment but HCV-RNA negative after 16-24 weeks of standard treatment.

Clinical Details

Official title: Optimization of Treatment for Patients With Chronic Hepatitis C Infected With HCV-genotype 2 or 3: 12 vs. 24 Weeks of Treatment Extension for Patients Without Rapid Virological Response

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Reduction of Relapse rate (HCV-RNA positive in serum by a standard HCV-PCR with a detection limit of at least 15 IU/ml) 24 weeks after the end of treatment and thus improvement of sustained virological response rates (SVR)

Secondary outcome:

Virological response rates (HCV-RNA negative in serum by a standard HCV-PCR with a detection limit of at least 15 IU/ml) at the end of therapy

Biochemical responses as determined by ALT and AST levels at the end of treatment and at the end of follow up.

Severity and frequency of adverse event

Analysis of quality of life

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Male and female patients with HCV-genotype 2/3 chronic hepatitis C documented by

detectable plasma HCV RNA (> 15 IU/mL) and positivity of anti-HCV antibodies

- Age Ôëą 18 years

- Compensated liver disease (Child-Pugh Grade A clinical classification)

- Negative urine or blood pregnancy test (one of the both; for women of childbearing

potential) documented within the 24-hour period prior to the first dose of study drug. Additionally, all fertile males and females must be using two forms of effective contraception during treatment and during the 7 months after treatment end. This includes using birth control pills (no interaction with investigational drugs), IUDs, condoms, diaphragms, or implants, being surgically sterilized, or being in a post-menopausal state. At least one contraception method must be of barrier method

- Ongoing treatment with 1. 5 ┬Ág/kg Peg-Interferon alpha-2b (PegIntron┬«) and > 10. 6

mg/kg ribavirin (Rebetol®)

- No rapid virological response (HCV-RNA positive after week 4 of the ongoing therapy)

- Willingness to give written informed consent and willingness to participate to and to

comply with the study protocol Exclusion Criteria:

- Women with ongoing pregnancy or breast feeding

- Male partners of women who are pregnant

- Positive tests at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, HBeAg,

anti-HIV, HIV-RNA

- History or other evidence of a medical condition associated with chronic liver

disease other than HCV associated (e. g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposures)

- History or other evidence of bleeding from esophageal varices or other conditions

consistent with decompensated liver disease

- Patients with liver cirrhosis with a lesion suspicious for hepatic malignancy on the

screening

- Absolute neutrophil count (ANC) <750 cells/mm3 at screening

- Platelet count <50,000 cells/mm3 at screening

- Hb <10 g/dl at screening

- Dose modification of Peg-Interferon alpha-2b (PegIntron®) or ribavirin (Rebetol®)

during the first 4 weeks of the ongoing therapy

- Interferon alpha or ribavirin therapy at any time point before the actual ongoing

treatment

- Less than 80% adherence to treatment of the ongoing treatment until randomization

(week 20-22 of ongoing treatment)

- Serum creatinine level >1. 5 times the upper limit of normal at screening

- History of severe psychiatric disease, especially depression (ICD 10 codes F30-F33).

Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time. Patients are excluded if any history of suicidal attempts is evident. If hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease are documented, psychiatric consultation is mandatory. Patients with a mild or moderate psychiatric disease (ICD 10 codes F32. 0, F32. 1, F33. 0, F33. 1) are only allowed to be included into the trial if a regular monitoring by a psychiatrist is performed during the trial

- History of a severe seizure disorder or current anticonvulsant use

- History of immunologically mediated disease (e. g., inflammatory bowel disease,

idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis)

- History or any other evidence of autoimmune diseases

- History or other evidence of chronic pulmonary disease associated with functional

limitation

- History of significant cardiac disease that could be worsened by acute anemia (e. g.

NYHA Functional Class III or IV, myocardial infarction within 6 months prior to treatment with Peg-Interferon/ribavirin therapy, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina)

- Evidence of thyroid disease that is poorly controlled on prescribed medications

- Evidence of severe retinopathy (e. g. CMV retinitis, macular degeneration)

- History of major organ transplantation with an existing functional graft

- History or other evidence of severe illness, malignancy or any other conditions which

would make the patient, in the opinion of the investigator, unsuitable for the study

- History of any systemic anti-neoplastic or immunomodulatory treatment (including

supraphysiologic doses of steroids and radiation) 6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study

- Patients with evidence for tuberculosis

- Drug abuse within 6 months prior to the first dose of study drug and excessive

alcohol consumption. Patients on methadone/polamidone/buprenorphine programs are not excluded

- Any investigational drug and/or participation in another clinical study prior 6

months to the actual ongoing antiviral treatment

- Limited contractual capability

Locations and Contacts

Charit├ę Campus Virchow-Klinikum, Med. Klinik f├╝r Gastroenterologie und Hepatologie, Berlin 13353, Germany

Hepatologische Schwerpunktpraxis im bng, Berlin 10969, Germany

Medizinisches Infektiologiezentrum, Berlin 10439, Germany

Praxis Dr. med. J. G├Âlz, Berlin 14057, Germany

Praxis Dr. med. Naumann, Berlin 10627, Germany

Praxis Meyer, Berlin 14057, Germany

├ärztehaus Leipziger Stra├če, Berlin 10117, Germany

Friedrich-Wilhelms-Universit├Ąt, Med. Klinik und Poliklinik I, Bonn 53105, Germany

Klinikum Bremen-Mitte gGmbH, Bremen 28205, Germany

Kreiskliniken Burghausen/Alt├Âtting, Med. Klinik II, Burghausen/Alt├Âtting 84489, Germany

Hepatologische Schwerpunktpraxis im bng, Dortmund 44263, Germany

Krankenhaus Dresden-Friedrichstadt, Dresden 01067, Germany

Fach├Ąrztliche Gemeinschaftspraxis, D├╝sseldorf 40223, Germany

Universit├Ątsklinikum Essen, Essen 45122, Germany

Klinikum der J.W. Goethe-Universit├Ąt, Frankfurt 60590, Germany

Vitanus GmbH, Frankfurt 60596, Germany

Praxis Zentrum Gastroenterologie und Endokrinologie, Freiburg 79098, Germany

Asklepios Klinik St. Georg, Institut f├╝r interdiziplin├Ąre Infektiologie, Hamburg 20099, Germany

IPM-Studycenter GmbH & Co. KG, Hamburg 20099, Germany

Universit├Ątsklinikum Hamburg-Eppendorf, Klinik f├╝r Innere Medizin, Hamburg 20246, Germany

Universt├Ątsklinikum Hamburg-Eppendorf;Innere Medizin, Hamburg 20246, Germany

Leberpraxis Hannover, Hannover 30161, Germany

Medizinische Hochschule Hannover, Zentrum Innere Medizin, Hannover 30625, Germany

Praxis Dr. med. S. Holm, Hannover 30159, Germany

Medizinische Fakult├Ąt der Universit├Ąt Heidelberg, Innere Medizin IV, Heidelberg 69120, Germany

Hepatologische Schwerpunktpraxis im bng, Herne 44623, Germany

Universit├Ątskliniken des Saarlandes, Innere Medizin II, Gastroenterologie, Homburg 66424, Germany

Klinik f├╝r Innere Medizin der FSU, Jena 07747, Germany

Gastroenterologische Gemeinschaftspraxis, Kiel 24146, Germany

Universit├Ątsklinikum Schleswig-Holstein, Campus Kiel, Klinik f├╝r Allgemeine Innere Medizin, Kiel 24105, Germany

Universit├Ątsklinikum Leipzig, Leipzig 04103, Germany

Gemeinschaftspraxis Dr.Simon, Leverkusen 51375, Germany

Universit├Ątklinikum Schleswig-Holstein, Campus L├╝beck, Med. Klinik I, L├╝beck 23538, Germany

Otto-von-Guericke Universit├Ąt Magdeburg, Magdeburg 39120, Germany

Klinikum der Johannes Gutenberg Universit├Ąt Med. Klinik, Mainz 55131, Germany

Universit├Ąts-Klinikum Mannheim, Med. Klinik II, Mannheim 68167, Germany

Hepatologische Schwerpunktpraxis im bng, Minden 32423, Germany

Klinikum Gro├čhadern, Med. Klinik 2, M├╝nchen 81366, Germany

Universit├Ątsklinikum M├╝nster, Med. Klinik und Poliklinik B, M├╝nster 48149, Germany

St.-Theresien-Krankenhaus, N├╝rnberg 90491, Germany

St. Josef Hospital, Oberhausen 46045, Germany

Hepatologische Schwerpunktpraxis im bng, Offenbach 63065, Germany

St.-Josefs-Klinik, Med. Klinik, Offenburg 77654, Germany

Universit├Ątsklinikum Regensburg, Klinik und Poliklinik f├╝r Innere Medizin I, Regensburg 93053, Germany

Diakoniekrankenhaus, Med. Klinik II, Rotenburg (Wuemme) 27356, Germany

Praxis Dr. med. A. Trein, Stuttgart 70197, Germany

Universit├Ątsklinikum T├╝bingen Medizinische Klinik I, T├╝bingen 70206, Germany

Universit├Ątsklinikum Ulm, Abteilung f├╝r Innere Medizin I, Ulm 89081, Germany

Med. Poliklinik der Universit├Ąt W├╝rzburg, W├╝rzburg 97080, Germany

Additional Information

The network of competence for hepatitis (Hep-Net) will support the nation-wide research of viral hepatitis and will develop uniform diagnostic and therapeutic standards for five years.

Related publications:

Aghemo A, Rumi MG, Soffredini R, D'Ambrosio R, Ronchi G, Del Ninno E, Gallus S, Colombo M. Impaired response to interferon-alpha2b plus ribavirin in cirrhotic patients with genotype 3a hepatitis C virus infection. Antivir Ther. 2006;11(6):797-802.

Choo QL, Kuo G, Weiner AJ, Overby LR, Bradley DW, Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A, non-B viral hepatitis genome. Science. 1989 Apr 21;244(4902):359-62.

Cornberg M, Deterding K, Manns MP. Present and future therapy for hepatitis C virus. Expert Rev Anti Infect Ther. 2006 Oct;4(5):781-93. Review.

Cornberg M, Wedemeyer H, Manns MP. Treatment of chronic hepatitis C with PEGylated interferon and ribavirin. Curr Gastroenterol Rep. 2002 Feb;4(1):23-30. Review.

Dalgard O, Bj├Şro 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.

Dalgard O, Bj├Şro K, Ring-Larsen H, Bjornsson E, Holberg-Petersen M, Skovlund E, Reichard O, Myrvang B, Sundel├Âf B, Ritland S, Hellum K, Fryd├ęn A, Florholmen J, Verbaan H; North-C Group. Pegylated interferon alfa and ribavirin for 14 versus 24 weeks in patients with hepatitis C virus genotype 2 or 3 and rapid virological response. Hepatology. 2008 Jan;47(1):35-42.

Davis GL, Albright JE, Cook SF, Rosenberg DM. Projecting future complications of chronic hepatitis C in the United States. Liver Transpl. 2003 Apr;9(4):331-8.

Hoofnagle JH. Hepatitis C: the clinical spectrum of disease. Hepatology. 1997 Sep;26(3 Suppl 1):15S-20S. Review.

Hoofnagle JH. Course and outcome of hepatitis C. Hepatology. 2002 Nov;36(5 Suppl 1):S21-9. Review.

Hoofnagle JH, Mullen KD, Jones DB, Rustgi V, Di Bisceglie A, Peters M, Waggoner JG, Park Y, Jones EA. Treatment of chronic non-A,non-B hepatitis with recombinant human alpha interferon. A preliminary report. N Engl J Med. 1986 Dec 18;315(25):1575-8.

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

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.

Manns MP, Rambusch EG. Autoimmunity and extrahepatic manifestations in hepatitis C virus infection. J Hepatol. 1999;31 Suppl 1:39-42. Review.

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.

Manns MP, Wedemeyer H, Cornberg M. Treating viral hepatitis C: efficacy, side effects, and complications. Gut. 2006 Sep;55(9):1350-9. Review.

Shepard CW, Finelli L, Alter MJ. Global epidemiology of hepatitis C virus infection. Lancet Infect Dis. 2005 Sep;5(9):558-67. Review.

Shiffman ML, Suter F, Bacon BR, Nelson D, Harley H, Solá 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.

von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, Bergk A, Bernsmeier C, H├Ąussinger 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.

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.

Starting date: November 2008
Last updated: March 18, 2015

Page last updated: August 23, 2015

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