Clinical trial NCT00803309: Study to Assess the Efficacy of 12 Versus 24 Weeks of Extended Treatment in HCV-Genotype 2/3 Patients
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hepatitis C, Chronic
Keywords: Chronic HCV-genotype 2/3
Efficacy of treatment extension
PegIntron
pegylated interferon alpha-2b
Rebetol
ribavirin
Lead sponsor: HepNet Study House, German Liverfoundation
Sponsor class: NETWORK
Collaborators: name: Hannover Medical School
First posted: 2008-12-05
Enrollment: 99
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: 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)
timeFrame: 48 weeks (arm A) or 36 weeks (arm B)
Secondary outcomes:
measure: 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
timeFrame: 24 weeks (arm A) or 12 weeks (arm B)
measure: Biochemical responses as determined by ALT and AST levels at the end of treatment and at the end of follow up.
timeFrame: Arm A: 24 and 24 weeks, arm B: 12 and 24 weeks
measure: Severity and frequency of adverse event
timeFrame: 48 weeks (arm A) or 36 weeks (arm B)
measure: Analysis of quality of life
timeFrame: 48 weeks (arm A) or 36 weeks (arm B)
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Ärztehaus Leipziger Straße
city: Berlin
country: Germany
facility: Medizinisches Infektiologiezentrum
city: Berlin
country: Germany
facility: Praxis Dr. med. Naumann
city: Berlin
country: Germany
facility: Hepatologische Schwerpunktpraxis im bng
city: Berlin
country: Germany
facility: Charité Campus Virchow-Klinikum, Med. Klinik für Gastroenterologie und Hepatologie
city: Berlin
country: Germany
facility: Praxis Dr. med. J. Gölz
city: Berlin
country: Germany
facility: Praxis Meyer
city: Bonn
country: Germany
facility: Friedrich-Wilhelms-Universität, Med. Klinik und Poliklinik I
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte gGmbH
city: Burghausen/Altötting
country: Germany
facility: Kreiskliniken Burghausen/Altötting, Med. Klinik II
city: Dortmund
country: Germany
facility: Hepatologische Schwerpunktpraxis im bng
city: Dresden
country: Germany
facility: Krankenhaus Dresden-Friedrichstadt
city: Düsseldorf
country: Germany
facility: Fachärztliche Gemeinschaftspraxis
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Frankfurt
country: Germany
facility: Klinikum der J.W. Goethe-Universität
city: Frankfurt
country: Germany
facility: Vitanus GmbH
city: Freiburg
country: Germany
facility: Praxis Zentrum Gastroenterologie und Endokrinologie
city: Hamburg
country: Germany
facility: Asklepios Klinik St. Georg, Institut für interdiziplinäre Infektiologie
city: Hamburg
country: Germany
facility: IPM-Studycenter GmbH & Co. KG
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Klinik für Innere Medizin
city: Hamburg
country: Germany
facility: Universtätsklinikum Hamburg-Eppendorf;Innere Medizin
city: Hannover
country: Germany
facility: Praxis Dr. med. S. Holm
city: Hannover
country: Germany
facility: Leberpraxis Hannover
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover, Zentrum Innere Medizin
city: Heidelberg
country: Germany
facility: Medizinische Fakultät der Universität Heidelberg, Innere Medizin IV
city: Herne
country: Germany
facility: Hepatologische Schwerpunktpraxis im bng
city: Homburg
country: Germany
facility: Universitätskliniken des Saarlandes, Innere Medizin II, Gastroenterologie
city: Jena
country: Germany
facility: Klinik für Innere Medizin der FSU
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Allgemeine Innere Medizin
city: Kiel
country: Germany
facility: Gastroenterologische Gemeinschaftspraxis
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Leverkusen
country: Germany
facility: Gemeinschaftspraxis Dr.Simon
city: Lübeck
country: Germany
facility: Universitätklinikum Schleswig-Holstein, Campus Lübeck, Med. Klinik I
city: Magdeburg
country: Germany
facility: Otto-von-Guericke Universität Magdeburg
city: Mainz
country: Germany
facility: Klinikum der Johannes Gutenberg Universität Med. Klinik
city: Mannheim
country: Germany
facility: Universitäts-Klinikum Mannheim, Med. Klinik II
city: Minden
country: Germany
facility: Hepatologische Schwerpunktpraxis im bng
city: München
country: Germany
facility: Klinikum Großhadern, Med. Klinik 2
city: Münster
country: Germany
facility: Universitätsklinikum Münster, Med. Klinik und Poliklinik B
city: Nürnberg
country: Germany
facility: St.-Theresien-Krankenhaus
city: Oberhausen
country: Germany
facility: St. Josef Hospital
city: Offenbach
country: Germany
facility: Hepatologische Schwerpunktpraxis im bng
city: Offenburg
country: Germany
facility: St.-Josefs-Klinik, Med. Klinik
city: Regensburg
country: Germany
facility: Universitätsklinikum Regensburg, Klinik und Poliklinik für Innere Medizin I
city: Rotenburg (Wuemme)
country: Germany
facility: Diakoniekrankenhaus, Med. Klinik II
city: Stuttgart
country: Germany
facility: Praxis Dr. med. A. Trein
city: Tübingen
country: Germany
facility: Universitätsklinikum Tübingen Medizinische Klinik I
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm, Abteilung für Innere Medizin I
city: Würzburg
country: Germany
facility: Med. Poliklinik der Universität Würzburg
Study officials:
affiliation: Hannover Medical School
name: Michael P. Manns, Prof. Dr.
role: STUDY_DIRECTOR
References:
citation: 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.