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

NCT ID: NCT00803309

Last Updated: 2017-08-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 99 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-11-30
• Study Completion Date: 2013-08-31

Brief 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.

Conditions

Hepatitis C, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

A

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

Group Type: ACTIVE_COMPARATOR

pegylated interferon alpha-2b

Intervention Type: DRUG

1.5 µg/kg once weekly, syringe, 24 weeks

Ribavirin

Intervention Type: DRUG

800-1400 mg per os, daily, tablets, 24 weeks

B

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

Group Type: ACTIVE_COMPARATOR

pegylated Interferon alpha-2b

Intervention Type: DRUG

1.5 µg/kg once weekly, syringe, 12 weeks

Ribavirin

Intervention Type: DRUG

800-1400 mg per os, daily, tablets, 12 weeks

Interventions

pegylated interferon alpha-2b

1.5 µg/kg once weekly, syringe, 24 weeks

Intervention Type: DRUG

Ribavirin

800-1400 mg per os, daily, tablets, 24 weeks

Intervention Type: DRUG

pegylated Interferon alpha-2b

1.5 µg/kg once weekly, syringe, 12 weeks

Intervention Type: DRUG

Ribavirin

800-1400 mg per os, daily, tablets, 12 weeks

Intervention Type: DRUG

Other Intervention Names

PegIntron; Rebetol; PegIntron; Rebetol

Eligibility 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 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hannover Medical School

OTHER

Sponsor Role: collaborator

HepNet Study House, German Liverfoundation

NETWORK

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael P. Manns, Prof. Dr.

Role: STUDY_DIRECTOR

Hannover Medical School

Locations

Ärztehaus Leipziger Straße

Berlin, , Germany

Medizinisches Infektiologiezentrum

Berlin, , Germany

Praxis Dr. med. Naumann

Berlin, , Germany

Hepatologische Schwerpunktpraxis im bng

Berlin, , Germany

Charité Campus Virchow-Klinikum, Med. Klinik für Gastroenterologie und Hepatologie

Berlin, , Germany

Praxis Dr. med. J. Gölz

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 im Breisgau, , 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

Praxis Dr. med. S. Holm

Hanover, , Germany

Leberpraxis Hannover

Hanover, , Germany

Medizinische Hochschule Hannover, Zentrum Innere Medizin

Hanover, , 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

Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Allgemeine Innere Medizin

Kiel, , Germany

Gastroenterologische Gemeinschaftspraxis

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

Nuremberg, , 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 (Wümme), , 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, , Germany

Countries

Germany

References

Heidrich B, Cordes HJ, Klinker H, Moller B, Naumann U, Rossle M, Kraus MR, Boker 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 Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial. PLoS One. 2015 Jun 9;10(6):e0128069. doi: 10.1371/journal.pone.0128069. eCollection 2015.

Reference Type: RESULT

PMID: 26057627 (View on PubMed)

Related Links

http://www.kompetenznetz-hepatitis.de

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.

Other Identifiers

P05498

Identifier Type: -

Identifier Source: org_study_id