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Study to Assess the Efficacy of 12 Versus 24 Weeks of Extended Treatment in HCV-Genotype 2/3 Patients (OPTEX2/3)
This study is currently recruiting participants.
Verified by Competence Network Viral Hepatitis, December 2008
Sponsors and Collaborators: Competence Network Viral Hepatitis
Hannover Clinical Trial Center GmbH
Information provided by: Competence Network Viral Hepatitis
ClinicalTrials.gov Identifier: NCT00803309
  Purpose

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 µg/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.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: pegylated interferon alpha-2b
Drug: Ribavirin
Drug: pegylated Interferon alpha-2b
Phase IV

MedlinePlus related topics: Hepatitis Hepatitis C
Drug Information available for: Ribavirin Interferon alfa-n1 Interferon alfa-2a Interferon alfa-2b Peginterferon Alfa-2b Interferons
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
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

Further study details as provided by Competence Network Viral Hepatitis:

Primary Outcome Measures:
  • 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) [ Time Frame: 48 weeks (arm A) or 36 weeks (arm B) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: 24 weeks (arm A) or 12 weeks (arm B) ] [ Designated as safety issue: No ]
  • Biochemical responses as determined by ALT and AST levels at the end of treatment and at the end of follow up. [ Time Frame: Arm A: 24 and 24 weeks, arm B: 12 and 24 weeks ] [ Designated as safety issue: No ]
  • Severity and frequency of adverse event [ Time Frame: 48 weeks (arm A) or 36 weeks (arm B) ] [ Designated as safety issue: Yes ]
  • Analysis of quality of life [ Time Frame: 48 weeks (arm A) or 36 weeks (arm B) ] [ Designated as safety issue: No ]

Estimated Enrollment: 150
Study Start Date: November 2008
Estimated Study Completion Date: July 2011
Estimated Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
A: Active Comparator
PegIntron® 1.5 µg/kg once weekly (QW) subcutaneous (sc) plus Rebetol® 800-1400 mg per os divided in 2 daily doses for additional 24 weeks beyond standard treatment with 24 weeks follow-up
Drug: pegylated interferon alpha-2b
1.5 µg/kg once weekly, syringe, 24 weeks
Drug: Ribavirin
800-1400 mg per os, daily, tablets, 24 weeks
B: Active Comparator
PegIntron® 1.5 µg/kg QW sc plus Rebetol® 800-1400 mg per os divided in 2 daily doses for additional 12 weeks beyond standard treatment with 24 weeks follow-up
Drug: pegylated Interferon alpha-2b
1.5 µg/kg once weekly, syringe, 12 weeks
Drug: Ribavirin
800-1400 mg per os, daily, tablets, 12 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 ≥ 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 µg/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 randomizaion (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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00803309

Contacts
Contact: Markus Cornberg, Dr. med. +49 511 532 6817 cornberg.markus@mh-hannover.de

Locations
Germany
Medizinische Hochschule Hannover, Zentrum Innere Medizin Recruiting
Hannover, Germany, 30625
Contact: M. P. Manns, Prof. Dr.            
Principal Investigator: M. P. Manns, Prof. Dr.            
Universitätsklinikum Aachen Recruiting
Aachen, Germany, 52074
Contact: Wasmuth, PD Dr.            
Principal Investigator: H. Wasmuth, PD Dr.            
Gastroenterologische Gemeinschaftspraxis Recruiting
Kiel, Germany, 24146
Contact: Hinrichsen, PD Dr.            
Principal Investigator: H. Hinrichsen, PD Dr.            
Charité Campus Virchow-Klinikum, Med. Klinik für Gastroenterologie und Hepatologie Recruiting
Berlin, Germany, 13353
Contact: Berg, Prof. Dr.            
Principal Investigator: T. Berg, Prof. Dr.            
Praxis Dr. med. J. Gölz Recruiting
Berlin, Germany, 14057
Contact: Gölz, Dr.            
Ärztehaus Leipziger Straße Recruiting
Berlin, Germany, 10117
Contact: John, Dr.            
Principal Investigator: C. John, Dr.            
Praxis Dr. med. U. Meyer Recruiting
Berlin, Germany, 10627
Contact: Meyer, Dr.            
Principal Investigator: U. Meyer, Dr.            
Hepatologische Schwerpunktpraxis im bng Recruiting
Berlin, Germany, 10969
Contact: Möller, Dr.            
Principal Investigator: B. Möller, Dr.            
Friedrich-Wilhelms-Universität, Med. Klinik und Poliklinik I Recruiting
Bonn, Germany, 53105
Contact: Spengler, Prof. Dr.            
Principal Investigator: U. Spengler, Prof. Dr.            
Klinikum Bremen-Mitte gGmbH Recruiting
Bremen, Germany, 28205
Contact: Ockenga, PD Dr.            
Principal Investigator: J. Ockenga, PD Dr.            
Krankenhaus Dresden-Friedrichstadt Recruiting
Dresden, Germany, 01067
Contact: Wollschläger, Dr.            
Principal Investigator: S. Wollschläger, Dr.            
Fachärztliche Gemeinschaftspraxis Recruiting
Düsseldorf, Germany, 40223
Contact: Carls, Dr.            
Principal Investigator: H. Carls, Dr.            
St. Josef Hospital Recruiting
Oberhausen, Germany, 46045
Contact: Niederau, Prof. Dr.            
Principal Investigator: C. Niederau, Prof. Dr.            
St.-Theresien-Krankenhaus Recruiting
Nürnberg, Germany, 90491
Contact: Norgauer, Dr.            
Principal Investigator: W. Norgauer, Dr.            
Universitätsklinikum Essen Recruiting
Essen, Germany, 45122
Contact: Gerken, Prof. Dr.            
Principal Investigator: G. Gerken, Prof. Dr.            
Hepatologische Schwerpunktpraxis im bng Recruiting
Offenbach, Germany, 63065
Contact: Leuschner, Dr.            
Principal Investigator: M. Leuschner, Dr.            
Vitanus GmbH Recruiting
Frankfurt, Germany, 60596
Contact: Cordes, Dr.            
Principal Investigator: H.-J. Cordes, Dr.            
Klinikum der J.W. Goethe-Universität Recruiting
Frankfurt, Germany, 60590
Contact: Zeuzem, Prof. Dr.            
Principal Investigator: S. Zeuzem, Prof. Dr.            
Praxis Zentrum Gastroenterologie und Endokrinologie Recruiting
Freiburg, Germany, 79098
Contact: Rössle, Prof. Dr.            
Principal Investigator: M. Rössle, Prof. Dr.            
Asklepios Klinik St. Georg, Institut für interdiziplinäre Infektiologie Recruiting
Hamburg, Germany, 20099
Contact: Stoehr, Dr.            
Principal Investigator: A. Stoehr, Dr.            
Universitätsklinikum Hamburg-Eppendorf, Klinik für Innere Medizin Recruiting
Hamburg, Germany, 20246
Contact: Lohse, Prof. Dr.            
Principal Investigator: A. Lohse, Prof. Dr.            
IPM-Studycenter GmbH & Co. KG Recruiting
Hamburg, Germany, 20099
Contact: Weitner, Dr.            
Principal Investigator: L. Weitner, Dr.            
Kreiskliniken Burghausen/Altötting, Med. Klinik II Recruiting
Burghausen/Altötting, Germany, 84489
Contact: Kraus, Prof. Dr.            
Principal Investigator: M. Kraus, Prof. Dr.            
Praxis Dr. med. S. Holm Recruiting
Hannover, Germany, 30159
Contact: Holm, Dr.            
Principal Investigator: S. Holm, Dr.            
Medizinische Fakultät der Universität Heidelberg, Innere Medizin IV Recruiting
Heidelberg, Germany, 69120
Contact: Eisenbach, Dr.            
Principal Investigator: C. Eisenbach, Dr.            
Klinik für Innere Medizin der FSU Recruiting
Jena, Germany, 07747
Contact: Stallmach, Prof. Dr.            
Principal Investigator: A. Stallmach, Prof. Dr.            
Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Allgemeine Innere Medizin Recruiting
Kiel, Germany, 24105
Contact: Günther, Dr.            
Principal Investigator: R. Günther, Dr.            
Universitätsklinikum Leipzig Recruiting
Leipzig, Germany, 04103
Contact: Wiegand, Dr.            
Principal Investigator: J. Wiegand, Dr.            
Universitätklinikum Schleswig-Holstein, Campus Lübeck, Med. Klinik I Recruiting
Lübeck, Germany, 23538
Contact: Schmidt, Dr.            
Principal Investigator: K. Schmidt, Dr.            
Otto-von-Guericke Universität Magdeburg Recruiting
Magdeburg, Germany, 39120
Contact: Malfertheiner, Prof. Dr.            
Principal Investigator: P. Malfertheiner, Prof. Dr.            
Universitäts-Klinikum Mannheim, Med. Klinik II Recruiting
Mannheim, Germany, 68167
Contact: Singer, Prof. Dr.            
Principal Investigator: M. Singer, Prof. Dr.            
Klinikum Großhadern, Med. Klinik 2 Recruiting
München, Germany, 81366
Contact: Zachoval, Prof. Dr.            
Principal Investigator: R. Zachoval, Prof. Dr.            
Zentrum für Interdisziplinäre Medizin Recruiting
Münster, Germany, 48143
Contact: Busch, Dr.            
Principal Investigator: H. Busch, Dr.            
Hepatologische Schwerpunktpraxis im bng Recruiting
Herne, Germany, 44623
Contact: Hüppe, Dr.            
Principal Investigator: D. Hüppe, Dr.            
Universitätsklinikum Münster, Med. Klinik und Poliklinik B Recruiting
Münster, Germany, 48149
Contact: Lügering, PD Dr.            
Principal Investigator: A. Lügering, PD Dr.            
Hepatologische Schwerpunktpraxis im bng Recruiting
Minden, Germany, 32423
Contact: Roggel, Dr.            
Principal Investigator: C. Roggel, Dr.            
Hepatologische Schwerpunktpraxis im bng Recruiting
Dortmund, Germany, 44263
Contact: Zehnter, Dr.            
Principal Investigator: E. Zehnter, Dr.            
Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin I Recruiting
Regensburg, Germany, 93053
Contact: Wiest, Dr.            
Principal Investigator: R. Wiest, Dr.            
Universitätskliniken des Saarlandes, Innere Medizin II, Gastroenterologie Recruiting
Homburg, Germany, 66424
Contact: Lammert, Prof. Dr.            
Principal Investigator: F. Lammert, Prof. Dr.            
St.-Josefs-Klinik, Med. Klinik Recruiting
Offenburg, Germany, 77654
Contact: Link, Dr.            
Principal Investigator: R. Link, Dr.            
Praxis Dr. med. A. Trein Recruiting
Stuttgart, Germany, 70197
Contact: Trein, Dr.            
Principal Investigator: A. Trein, Dr.            
Universitätsklinikum Ulm, Abteilung für Innere Medizin I Recruiting
Ulm, Germany, 89081
Contact: Dikopoulos, Dr.            
Principal Investigator: N. Dikopoulos, Dr.            
Med. Poliklinik der Universität Würzburg Recruiting
Würzburg, Germany, 97080
Contact: Kliniker, Prof. Dr.            
Principal Investigator: H. Kliniker, Prof. Dr.            
Diakoniekrankenhaus, Med. Klinik II Recruiting
Rotenburg (Wuemme), Germany, 27356
Contact: Arnold, Prof. Dr.            
Principal Investigator: J. Arnold, Prof. Dr.            
Sponsors and Collaborators
Competence Network Viral Hepatitis
Hannover Clinical Trial Center GmbH
Investigators
Study Director: Michael P. Manns, Prof. Dr. Hannover Medical School
  More 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.  This link exits the ClinicalTrials.gov site

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, 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.
Dalgard O, Bjøro K, Ring-Larsen H, Bjornsson E, Holberg-Petersen M, Skovlund E, Reichard O, Myrvang B, Sundelöf B, Ritland S, Hellum K, Frydén 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. No abstract available.
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, 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.
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.
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.

Responsible Party: Hep-Net ( Prof. Dr. med. M. P. Manns )
Study ID Numbers: P05498
Study First Received: December 4, 2008
Last Updated: December 4, 2008
ClinicalTrials.gov Identifier: NCT00803309  
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Competence Network Viral Hepatitis:
Chronic HCV-genotype 2/3
Efficacy of treatment extension
PegIntron
Rebetol

Study placed in the following topic categories:
Interferon-alpha
Liver Diseases
Hepatitis, Chronic
Interferons
Ribavirin
Hepatitis, Viral, Human
Hepatitis
Virus Diseases
Digestive System Diseases
Peginterferon alfa-2b
Hepatitis C
Interferon Alfa-2a
Hepatitis C, Chronic
Interferon Alfa-2b

Additional relevant MeSH terms:
Antimetabolites
Anti-Infective Agents
RNA Virus Infections
Molecular Mechanisms of Pharmacological Action
Flaviviridae Infections
Immunologic Factors
Antineoplastic Agents
Growth Substances
Physiological Effects of Drugs
Antiviral Agents
Angiogenesis Inhibitors
Pharmacologic Actions
Therapeutic Uses
Angiogenesis Modulating Agents
Growth Inhibitors

ClinicalTrials.gov processed this record on January 16, 2009