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

Hepatitis C, Chronic Clinical Trial

— OPTEX2/3  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00803309
• Other study ID #: P05498
• Status: Terminated
• Phase: Phase 4
• First received: December 4, 2008
• Last updated: August 25, 2017
• Start date: November 2008
• Est. completion date: August 2013

Study information

• Verified date: August 2017
• Source: HepNet Study House, German Liverfoundation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 99
• Est. completion date: August 2013
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic

Intervention

Drug:
• pegylated interferon alpha-2b
1.5 µg/kg once weekly, syringe, 24 weeks
• Ribavirin
800-1400 mg per os, daily, tablets, 24 weeks
• pegylated Interferon alpha-2b
1.5 µg/kg once weekly, syringe, 12 weeks
• Ribavirin
800-1400 mg per os, daily, tablets, 12 weeks

Locations

Country	Name	City	State
Germany	Ärztehaus Leipziger Straße	Berlin
Germany	Charité Campus Virchow-Klinikum, Med. Klinik für Gastroenterologie und Hepatologie	Berlin
Germany	Hepatologische Schwerpunktpraxis im bng	Berlin
Germany	Medizinisches Infektiologiezentrum	Berlin
Germany	Praxis Dr. med. J. Gölz	Berlin
Germany	Praxis Dr. med. Naumann	Berlin
Germany	Praxis Meyer	Berlin
Germany	Friedrich-Wilhelms-Universität, Med. Klinik und Poliklinik I	Bonn
Germany	Klinikum Bremen-Mitte gGmbH	Bremen
Germany	Kreiskliniken Burghausen/Altötting, Med. Klinik II	Burghausen/Altötting
Germany	Hepatologische Schwerpunktpraxis im bng	Dortmund
Germany	Krankenhaus Dresden-Friedrichstadt	Dresden
Germany	Fachärztliche Gemeinschaftspraxis	Düsseldorf
Germany	Universitätsklinikum Essen	Essen
Germany	Klinikum der J.W. Goethe-Universität	Frankfurt
Germany	Vitanus GmbH	Frankfurt
Germany	Praxis Zentrum Gastroenterologie und Endokrinologie	Freiburg
Germany	Asklepios Klinik St. Georg, Institut für interdiziplinäre Infektiologie	Hamburg
Germany	IPM-Studycenter GmbH & Co. KG	Hamburg
Germany	Universitätsklinikum Hamburg-Eppendorf, Klinik für Innere Medizin	Hamburg
Germany	Universtätsklinikum Hamburg-Eppendorf;Innere Medizin	Hamburg
Germany	Leberpraxis Hannover	Hannover
Germany	Medizinische Hochschule Hannover, Zentrum Innere Medizin	Hannover
Germany	Praxis Dr. med. S. Holm	Hannover
Germany	Medizinische Fakultät der Universität Heidelberg, Innere Medizin IV	Heidelberg
Germany	Hepatologische Schwerpunktpraxis im bng	Herne
Germany	Universitätskliniken des Saarlandes, Innere Medizin II, Gastroenterologie	Homburg
Germany	Klinik für Innere Medizin der FSU	Jena
Germany	Gastroenterologische Gemeinschaftspraxis	Kiel
Germany	Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Allgemeine Innere Medizin	Kiel
Germany	Universitätsklinikum Leipzig	Leipzig
Germany	Gemeinschaftspraxis Dr.Simon	Leverkusen
Germany	Universitätklinikum Schleswig-Holstein, Campus Lübeck, Med. Klinik I	Lübeck
Germany	Otto-von-Guericke Universität Magdeburg	Magdeburg
Germany	Klinikum der Johannes Gutenberg Universität Med. Klinik	Mainz
Germany	Universitäts-Klinikum Mannheim, Med. Klinik II	Mannheim
Germany	Hepatologische Schwerpunktpraxis im bng	Minden
Germany	Klinikum Großhadern, Med. Klinik 2	München
Germany	Universitätsklinikum Münster, Med. Klinik und Poliklinik B	Münster
Germany	St.-Theresien-Krankenhaus	Nürnberg
Germany	St. Josef Hospital	Oberhausen
Germany	Hepatologische Schwerpunktpraxis im bng	Offenbach
Germany	St.-Josefs-Klinik, Med. Klinik	Offenburg
Germany	Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin I	Regensburg
Germany	Diakoniekrankenhaus, Med. Klinik II	Rotenburg (Wuemme)
Germany	Praxis Dr. med. A. Trein	Stuttgart
Germany	Universitätsklinikum Tübingen Medizinische Klinik I	Tübingen
Germany	Universitätsklinikum Ulm, Abteilung für Innere Medizin I	Ulm
Germany	Med. Poliklinik der Universität Würzburg	Würzburg

Sponsors (2)

Lead Sponsor	Collaborator
HepNet Study House, German Liverfoundation	Hannover Clinical Trial Center GmbH

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Heidrich B, Cordes HJ, Klinker H, Möller B, Naumann U, Rössle M, Kraus MR, Böker KH, Roggel C, Schuchmann M, Stoehr A, Trein A, Hardtke S, Gonnermann A, Koch A, Wedemeyer H, Manns MP, Cornberg M. Treatment Extension of Pegylated Interferon Alpha and Ribav — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)		48 weeks (arm A) or 36 weeks (arm B)
Secondary	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		24 weeks (arm A) or 12 weeks (arm B)
Secondary	Biochemical responses as determined by ALT and AST levels at the end of treatment and at the end of follow up.		Arm A: 24 and 24 weeks, arm B: 12 and 24 weeks
Secondary	Severity and frequency of adverse event		48 weeks (arm A) or 36 weeks (arm B)
Secondary	Analysis of quality of life		48 weeks (arm A) or 36 weeks (arm B)

External Links

•   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.