Study for Patients With Chronic HCV (GT 1 or 3) Who Relapsed to Previous (Peg)Interferon/ Ribavirin Combination Therapy

Hepatitis C, Chronic Clinical Trial

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.

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00299923
• Other study ID #: ML 18545 (TRELA)
• Secondary ID: EudraCT-Nr.: 200
• Status: Active, not recruiting
• Phase: Phase 3
• First received: March 6, 2006
• Last updated: March 8, 2007
• Start date: November 2005

Study information

• Verified date: March 2007
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 300
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis C, Chronic
• Relapse

Intervention

Drug:
• Peginterferon alfa-2a, Ribavirin, Amantadine

Locations

Country	Name	City	State
Germany	Universitätsklinikum des Saarlandes	Bad Homburg/ Saar	Saarland
Germany	Charité, Campus Benjamin Franklin	Berlin
Germany	Charité, Campus Virchow-Klinikum, Med. Klinik (Gastroenterologie/ Hepatologie)	Berlin
Germany	Praxis Möller/ Heyne	Berlin
Germany	Klinikum der Ruhr-Universität Bochum	Bochum	Nordrhein-Westfalen
Germany	Universitätsklinikum Bonn	Bonn	Nordrhein-Westfalen
Germany	Klinikum Bremen-Mitte	Bremen
Germany	Universitätsklinikum Erlangen	Erlangen	Bayern
Germany	J. W.-Goethe-Universität	Frankfurt	Hessen
Germany	Universitätsklinikum Freiburg	Freiburg	Baden-Württemberg
Germany	Klinikum der Medizinischen Fakultät der Martin-Luther Universität Halle-Wittenberg	Halle (Saale)	Sachsen-Anhalt
Germany	Universitätsklinikum Hamburg-Eppendorf, Med. Klinik 1	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover	Niedersachsen
Germany	Universitätsklinikum Heidelberg	Heidelberg	Baden-Württembeg
Germany	Universitätsklinikum Schleswig-Holstein	Kiel	Schleswig-Holstein
Germany	Klinikum der Universität Köln	Köln	Nordrhein-Westfalen
Germany	Universitätsklinikum Schleswig-Holstein, Campus Lübeck	Lübeck	Schleswig-Holstein
Germany	Johannes Gutenberg-Universität Mainz	Mainz	Rheinland-Pfalz
Germany	Universitätsklinikum Mannheim	Mannheim	Baden-Würtemberg
Germany	Klinikum rechts der Isar der TU München	München	Bayern
Germany	Universitätsklinkum Münster	Münster	Nordrhein-Westfalen
Germany	St-Josef-Hospital	Oberhausen	Nordrhein-Westfalen
Germany	Klinikum der Universität Regensburg	Regensburg	Bayern
Germany	Krankenhaus Barmherzige Brüder	Regensburg	Bayern
Germany	Universität Rostock	Rostock	Mecklenburg-Vorpommern
Germany	Universitätsklinikum Ulm	Ulm	Baden-Württemberg
Germany	Klinikum der Universität Würzburg	Würzburg	Bayern

Sponsors (3)

Lead Sponsor	Collaborator
University of Hamburg	Hoffmann-La Roche, Universitätsklinikum Hamburg-Eppendorf

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	- 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	relationship between EVR during the first twelve weeks and SVR
Secondary	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.