Clinical trial NCT00299923: Study for Patients With Chronic HCV (GT 1 or 3) Who Relapsed to Previous (Peg)Interferon/ Ribavirin Combination Therapy
Official title: Randomized, Open-Label, Multicenter Study Examining the Effects of Duration of Treatment of PEGASYS® in Combination With Daily COPEGUS® + Amantadine in Patients With Chronic HCV After Relapse to Previous (Peg)IFN + Ribavirin Therapy.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Hepatitis C, Chronic
Relapse
Keywords: drug therapy
Interferon
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: Universitätsklinikum Hamburg-Eppendorf
name: Hoffmann-La Roche
First posted: 2006-03-07
Enrollment: 300
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: The aim of this study is, to compare the relapse rate in chronic HCV patients with genotype 1 or 3 under the combination of standard dose Peg-Interferon alfa-2a (PEG-IFN alfa-2a), Ribavirin (RBV) and Amantadine (AMA) given for 72 weeks (group A), versus the same combination, given for 48 weeks (group B) in patients who relapsed to previous combination therapy to conventional or pegylated (PEG) Interferon alfa and Ribavirin. Relapse ist defined as percentage of patients with non-detectable HCV-RNA at end of therapy (week 48 GT1/ week 24 GT 3) who become HCV-RNA positive during a follow-up period of 24 weeks.


Eligibility criteria: Inclusion Criteria:

* Relapsers to previous combination therapy with (PEG-)IFN alfa-/Ribavirin and a negative HCV-RNA test result at the end of this regular treatment course and positive HCV-RNA test result during the follow-up period.
* Termination of (PEG-)IFN alfa-/ribavirin therapy at least 3 months prior to enrolment
* Chronic HCV infection genotype 1 or 3.
* Serum HCV-RNA quantifiable at \>100 IU/mL by COBAS AmpliPrep or another quantitative HCV-RNA PCR test (reported in IU)
* Compensated liver disease (Child-Pugh A)
* Exclusion of HCC in patients with cirrhosis or transition to cirrhosis. In patients with AFP \>50 ng/mL an established assay for exclusion of HCC has to be done
* Negative urine or blood pregnancy test
* All fertile males and females must use two reliable forms of effective contraception (combined) during treatment with study drugs and 6 months post treatment

Exclusion Criteria (at screening):

* Hypersensitiveness to Interferon, PEG-IFN alfa-2a, Ribavirin and Amantadine or other ingredient of the drugs
* Ongoing pregnancy or breast feeding
* Male partners of women who are pregnant or with women without effective contraception
* Signs or symptoms of hepatocellular carcinoma
* Chronic HCV infection genotype 2, 4, 5 or 6
* Therapy with any systemic anti-viral, anti-neoplastic or immunomodulatory treatment \< 6 months prior to the first dose of study drug and during study period. Exception: patients who have had a limited (\< 7 days) course of acyclovir or valacyclovir for herpetic lesions \< 1 month prior to the first administration of test drug are not excluded.
* Any investigational drug \< 6 weeks prior to the first dose of study drug
* Positive test for anti-HAV IgM, HBsAg, anti-HBc IgM, anti-HIV
* History or other evidence of a medical condition associated with chronic liver disease other than HCV
* History or other evidence of decompensated liver disease or a Child-Pugh score \> 6.
* Hb \<12 g/dL (\<120 g/L) in women or \<13 g/dL (\<130 g/L) in men at screening
* Any patient with an increased baseline risk for anemia or for whom anemia would be medically problematic
* Neutrophil count \<1,500 cells/mm3 and/or platelet count \<90,000 cells/mm3
* Serum creatinin concentration \>1.5 mg/dl
* History of severe psychiatric disease, especially depression.
* History of a severe seizure disorder that can not be stabilized by medication
* History of immunologically mediated disease
* Chronic pulmonary disease associated with functional limitation
* History of severe cardiac disease
* History of major organ transplantation except corneatransplantation
* Evidence of severe illness, malignancy, or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study
* Thyroid dysfunction not adequately controlled
* Evidence of severe retinopathy or clinically relevant ophthalmological disorder due to diabetes mellitus or hypertension
* Evidence of active drug abuse within one year of study entry except of a prescribed stable opioid substitution
* Take of Memantine during study period
* Cardiomyopathy and myocarditis
* AV-Block II° and III°
* Pre-existing bradycardia \< 55 counts/min
* Known QT-interval (QTc after Bazett \> 420 ms) or recognized U-waves or congenital QT-syndrome
* History of severe ventricular arrhythmia incl. Torsade de pointes
* Simultaneous therapy with Budipin or other medicine that extend the QT-interval like (e.g.antiarrhythmic drugs class IA and class III, antipsychotic drugs, tri- and tetracyclic antidepressants, antihistaminics, macrolide, gyrase inhibitors, Azol-antimykotics)
* Patients with obstructive glaucoma
* Patients with excitableness and confusion
* Patients with delirium and exogenic psychosis in the anamnesis
* Prostataadenome
* Diuretic medication of the type combination Triamterene/ Hydrochlorothiazide
* Inability or unwillingness to provide informed consent or abide by the requirements of the study

Primary outcomes:
measure: - Comparison of the rate of relapse under the combination of standard dose PegIFN alfa-2a, Ribavirin and Amantadine given for 72 vs. 48 weeks.
Secondary outcomes:
measure: relationship between EVR during the first twelve weeks and SVR
measure: virological response to the combination of standard dose defined as reduction of HCV RNA at week 4, 12, 24, 48 and 72 of treatment, separated between HCV-Genotypes.
Other outcomes:
Locations:
city: Mannheim
country: Germany
facility: Universitätsklinikum Mannheim
state: Baden-Würtemberg
city: Heidelberg
country: Germany
facility: Universitätsklinikum Heidelberg
state: Baden-Württembeg
city: Freiburg
country: Germany
facility: Universitätsklinikum Freiburg
state: Baden-Württemberg
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
state: Baden-Württemberg
city: Erlangen
country: Germany
facility: Universitätsklinikum Erlangen
state: Bayern
city: München
country: Germany
facility: Klinikum rechts der Isar der TU München
state: Bayern
city: Regensburg
country: Germany
facility: Krankenhaus Barmherzige Brüder
state: Bayern
city: Regensburg
country: Germany
facility: Klinikum der Universität Regensburg
state: Bayern
city: Würzburg
country: Germany
facility: Klinikum der Universität Würzburg
state: Bayern
city: Frankfurt
country: Germany
facility: J. W.-Goethe-Universität
state: Hessen
city: Rostock
country: Germany
facility: Universität Rostock
state: Mecklenburg-Vorpommern
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
state: Niedersachsen
city: Bochum
country: Germany
facility: Klinikum der Ruhr-Universität Bochum
state: Nordrhein-Westfalen
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
state: Nordrhein-Westfalen
city: Köln
country: Germany
facility: Klinikum der Universität Köln
state: Nordrhein-Westfalen
city: Münster
country: Germany
facility: Universitätsklinkum Münster
state: Nordrhein-Westfalen
city: Oberhausen
country: Germany
facility: St-Josef-Hospital
state: Nordrhein-Westfalen
city: Mainz
country: Germany
facility: Johannes Gutenberg-Universität Mainz
state: Rheinland-Pfalz
city: Bad Homburg/ Saar
country: Germany
facility: Universitätsklinikum des Saarlandes
state: Saarland
city: Halle (Saale)
country: Germany
facility: Klinikum der Medizinischen Fakultät der Martin-Luther Universität Halle-Wittenberg
state: Sachsen-Anhalt
city: Kiel
country: Germany
facility: Universitätsklinikum Schleswig-Holstein
state: Schleswig-Holstein
city: Lübeck
country: Germany
facility: Universitätsklinikum Schleswig-Holstein, Campus Lübeck
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: Praxis Möller/ Heyne
city: Berlin
country: Germany
facility: Charité, Campus Benjamin Franklin
city: Berlin
country: Germany
facility: Charité, Campus Virchow-Klinikum, Med. Klinik (Gastroenterologie/ Hepatologie)
city: Bremen
country: Germany
facility: Klinikum Bremen-Mitte
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg-Eppendorf, Med. Klinik 1
Study officials:
affiliation: Universitätsklinikum Hamburg-Eppendorf, Medizinische Klinik 1
name: Peter Buggisch, Dr.
role: PRINCIPAL_INVESTIGATOR
References: