A Study of Debio 025 (Alisporivir) Combined With Peg-IFNα2a and Ribavirin in Treatment naïve Chronic Hepatitis C Genotype 1 Patients

NCT ID: NCT00854802

Last Updated: 2016-02-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

290 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-01-31

Study Completion Date

2010-09-30

Brief Summary

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The purpose of this study is to compare several Debio 025 (alisporivir)/peg-IFNα2a/ribavirin triple therapies with the current standard of care (SOC) in treatment naïve chronic hepatitis C genotype 1 patients.

Detailed Description

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This is an international, multicentre, randomised, double-blind, placebo-controlled, 4-arm, parallel-group, multiple dose phase II study comparing 3 Debio 025 (alisporivir)/peg-IFNα2a/ribavirin regimens to SOC treatment in treatment naïve chronic HCV genotype 1 patients.

Patients are randomised into 1 of 4 arms receiving either Debio 025/peg-IFNα2a/ribavirin triple therapy for a fixed treatment duration of 48 weeks (Treatment A) or 24 weeks (Treatment B), Debio 025/peg-IFNα2a/ribavirin triple therapy for a response-based treatment duration of 24 or 48 weeks (Treatment C), or blinded SOC treatment for 48 weeks (Treatment D). Follow-up is 24 weeks in all treatment arms.

Conditions

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Chronic Hepatitis C

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Debio 025 600 mg + peg-IFNα2a + ribavirin - 48 weeks

Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 47 weeks + peg-IFNα2a 180 µg subcutaneously (sc) once weekly for 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 48 weeks.

Group Type EXPERIMENTAL

Debio 025

Intervention Type DRUG

Debio 025 supplied in soft gel capsules

Peg-IFNα2a

Intervention Type DRUG

Peg-IFNα2a supplied in pre-filled syringes

Ribavirin

Intervention Type DRUG

Ribavirin supplied in tablets

Debio 025 600 mg + peg-IFNα2a + ribavirin - 24 weeks

Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 23 weeks + peg-IFNα2a 180 µg sc once weekly for 24 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 24 weeks.

Group Type EXPERIMENTAL

Debio 025

Intervention Type DRUG

Debio 025 supplied in soft gel capsules

Peg-IFNα2a

Intervention Type DRUG

Peg-IFNα2a supplied in pre-filled syringes

Ribavirin

Intervention Type DRUG

Ribavirin supplied in tablets

Debio 025 600 mg + peg-IFNα2a + ribavirin - 24 or 48 weeks

Participants receive Debio 025 600 mg orally twice daily for 7 days (loading dose) followed by Debio 025 600 mg orally once daily for 23 or 47 weeks + peg-IFNα2a 180 µg sc once weekly for 24 or 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 24 or 48 weeks. Participants who achieve a rapid viral response, defined as having undetectable hepatitis C virus RNA at week 4, are treated for 24 weeks; other patients are treated for 48 weeks.

Group Type EXPERIMENTAL

Debio 025

Intervention Type DRUG

Debio 025 supplied in soft gel capsules

Peg-IFNα2a

Intervention Type DRUG

Peg-IFNα2a supplied in pre-filled syringes

Ribavirin

Intervention Type DRUG

Ribavirin supplied in tablets

Debio 025 placebo + peg-IFNα2a + ribavirin - 48 weeks

Participants receive Debio 025 placebo orally twice daily for 7 days followed by Debio 025 placebo orally once daily for 47 weeks + peg-IFNα2a 180 µg subcutaneously (sc) once weekly for 48 weeks + ribavirin 1000 or 1200 mg (weight based) orally daily for 48 weeks.

Group Type PLACEBO_COMPARATOR

Peg-IFNα2a

Intervention Type DRUG

Peg-IFNα2a supplied in pre-filled syringes

Ribavirin

Intervention Type DRUG

Ribavirin supplied in tablets

Debio 025 placebo

Intervention Type DRUG

Debio 025 placebo supplied in soft gel capsules

Interventions

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Debio 025

Debio 025 supplied in soft gel capsules

Intervention Type DRUG

Peg-IFNα2a

Peg-IFNα2a supplied in pre-filled syringes

Intervention Type DRUG

Ribavirin

Ribavirin supplied in tablets

Intervention Type DRUG

Debio 025 placebo

Debio 025 placebo supplied in soft gel capsules

Intervention Type DRUG

Other Intervention Names

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Alisporivir Pegasys Copegus Rebetol Ribasphere Vilona Virazole

Eligibility Criteria

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Inclusion Criteria

* Males or females aged ≥ 18 and ≤ 65 years.
* Body mass index (BMI) ≥ 18 and ≤ 32 kg/m\^2.
* Hepatitis B surface antigen (HbsAg) negative and HIV-1 negative.
* Serological diagnosis of chronic hepatitis C viral infection genotype 1 for \> 6 months.
* Chronic liver disease consistent with chronic hepatitis C infection on a biopsy or FibroScan® obtained within the past 24 months (36 months for patients with incomplete/transition to cirrhosis).
* Previously untreated for hepatitis C virus (HCV) infection (approved or investigational drug).
* Plasma HCV RNA level lower limit ≥ 100 IU/ml assessed by quantitative polymerase chain reaction (qPCR) or equivalent; no upper limit.
* Neutrophil count ≥ 1500/µL; hemoglobin (Hb) ≥ 12g/dL for females and ≥ 13g/dL for males; platelets ≥ 90,000/µL.
* Patients with incomplete/transition to cirrhosis on biopsy or an elasticity score between 9.5 and 14 kPa on FibroScan must have an abdominal ultrasound (US), computed tomographic (CT) scan, or magnetic resonance imaging (MRI) scan without evidence of hepatocellular carcinoma (within 2 months prior to randomisation) and a serum alpha-foetoprotein (AFP) \< 100 ng/mL.
* Aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) \< 5 times the upper limit of normal.
* Normal or compensated liver function and absence of complicated portal hypertension as documented by the following:

* No history of bleeding oesophageal varices;
* Absence of ascites;
* Absence of encephalopathy;
* Albumin ≥ 35 g/L;
* Total bilirubin ≤ 1.8 mg/dL (≤ 30 µmol/L);
* Prothrombin (INR ≤ 1.5).
* Creatinine clearance \> 50 mL/min.
* Thyroid stimulating hormone (TSH) within normal range;
* All patients should be informed about Debio 025 and ribavirin foetotoxicity:

* Females may participate if they are surgically sterile or post-menopausal. Pre-menopausal females may participate if they use 2 reliable contraceptive methods (oral contraceptive + barrier method). The contraceptive regimen must be maintained during the treatment period and for 4 months after the last Debio 025 or ribavirin dose.
* Male patients must be surgically sterile or use 2 reliable contraceptive methods (oral contraceptive + barrier method). The contraceptive regimen must be maintained during the treatment period and for 7 months after the last Debio 025 or ribavirin dose.
* Signed informed consent before any study procedures.
* Negative pregnancy test within one week of first investigational product administration for female patients of child bearing potential.

Exclusion Criteria

* Treatment with any investigational drug within 6 months prior to the first dose of investigational product.
* HCV genotype different from genotype 1.
* Any previous HCV treatment (approved or investigational).
* Histologic evidence of complete hepatic cirrhosis (including compensated cirrhosis) based on a previous liver biopsy (if available).
* Ongoing or recent use of any other medication (including over the counter medication and herbal products) within 2 weeks before study start or within 5 drug half-lives of that medication (whichever is longer) that are known inhibitors/inducers of cytochrome P450 (CYP450) 3A, substrates of P-glycoprotein 1 (P-gP), or substrates/inhibitors of organic anion-transporting polypeptides (OATP), multidrug resistance-associated protein 2 (MRP2), or bile salt export pump (BSEP) and are mentioned in the list of unauthorised medications;
* Any medical contraindications to peg-IFNα2a and/or ribavirin treatment;
* Any other cause of relevant liver disease other than HCV including but not limited to hepatitis B virus (HBV), drug- or alcohol-related cirrhosis, autoimmune hepatitis, haemochromatosis, Wilson's disease, nonalcoholic steatohepatitis (NASH), primary sclerosing cholangitis (PSC), or primary biliary cirrhosis (PBC).
* Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrollment or could interfere with the patient participating in and completing the study. Patients with risk factors (hypertension or diabetes) need to have an ophthalmologic investigation (including fundoscopy).
* History of moderate, severe, or uncontrolled psychiatric disease, especially depression, including a history of hospitalisation or prior suicidal attempt.
* Uncontrolled arterial hypertension, ie, patients with systolic BP ≥ 160 mmHg and/or diastolic BP ≥ 100 mmHg.
* History of pancreatitis, uncontrolled diabetes mellitus, or retinopathy.
* Anti-nuclear antibody (ANA) titre \> 1:640 at screening and/or evidence of autoimmune hepatitis on liver biopsy.
* Alcohol consumption \> 20 g/day for females and \> 30 g/day for males.
* History of major organ transplantation with an existing functional graft.
* Pregnancy or lactation.
* Haemoglobinopathies (thalassaemia major, sickle cell anaemia or drepanocytosis).
* Familial history of severe neonatal cholestasis or pregnancy cholestasis.
* Evidence of an active or suspected cancer, or a history of malignancy where the risk of recurrence is ≥ 20% within 2 years.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Parexel

INDUSTRY

Sponsor Role collaborator

Debiopharm International SA

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Rafael Crabbé, MD

Role: STUDY_DIRECTOR

Debiopharm International SA

Locations

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Cliniques Universitaires Saint-Luc

Brussels, , Belgium

Site Status

UZ Gent

Ghent, , Belgium

Site Status

C.H.U - Hôpital Henri-Mondor

Créteil, , France

Site Status

C.H.U de Lyon Hôpital de l'Hôtel Dieu

Lyon, , France

Site Status

Hôpital de l'Archet 2

Nice, , France

Site Status

C.H.U Hôpital Cochin

Paris, , France

Site Status

C.H.U - Hôpital Saint Antoine

Paris - Saint Antoine, , France

Site Status

Hôpital du Haut-Levêque - C.H.U de Bordeaux

Pessac, , France

Site Status

C.H.U de Nancy-Hôpital Brabois

Vandœuvre-lès-Nancy, , France

Site Status

Charité - Universitatsmedizin Berlin

Berlin, , Germany

Site Status

Universitätsklinikum Düsseldorf

Düsseldorf, , Germany

Site Status

Center for HIV and Hepatogastroenterology

Düsseldorf, , Germany

Site Status

Universitätsklinikum Essen

Essen, , Germany

Site Status

J.W. Goethe University Hospital

Frankfurt am Main, , Germany

Site Status

Albert-Ludwigs-Universität Freiburg, Universitätsk

Freiburg im Breisgau, , Germany

Site Status

Medizinische Hochschule Hannover

Hanover, , Germany

Site Status

Medizinische Universitätsklinik

Heidelberg, , Germany

Site Status

Johannes Gutenberg-Universitaet Mainz

Mainz, , Germany

Site Status

Policlinico S.Orsola Malpighi

Bologna, , Italy

Site Status

Mangiagalli e Regina Elena di Milano

Milan, , Italy

Site Status

Seconda Università di Napoli- Secondo Policlinico

Napoli, , Italy

Site Status

"Policlinico ""Paolo Giaccone"" dell'Università di

Palermo, , Italy

Site Status

Az. Osp. Universitaria S. Giovanni Battista

Torino, , Italy

Site Status

Wojewódzki Szpital Specjalistyczny im. K. Dluskieg

Bialystok, , Poland

Site Status

Wojewódzki Szpital Obserwacyjno-Zakazny im. Tadeus

Bydgoszcz, , Poland

Site Status

Szpital Specjalistyczny w Chorzowie

Chorzów, , Poland

Site Status

Wojewódzki Szpital Zespolony w Kielcach

Kielce, , Poland

Site Status

Krakowski Szpital Specjalistyczny im. Jana Pawla I

Krakow, , Poland

Site Status

Wojewódzki Szpital Specjalstyczny im. Wl. Biegansk

Lódz, , Poland

Site Status

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Woj

Warsaw, , Poland

Site Status

Spitalul Clinic Colentina

Bucharest, , Romania

Site Status

Institutul Clinic Fundeni

Bucharest, , Romania

Site Status

Centrul de Diagnostic si Tratament Dr. Victor Babe

Bucharest, , Romania

Site Status

"Spitalul Clinic de Urgenta ""Prof. dr. Octavian F

Cluj-Napoca, , Romania

Site Status

Institutul de Gastroenterologie si Hepatologie

Iași, , Romania

Site Status

Hospital Universitari Vall d'Hebrón

Barcelona, , Spain

Site Status

Hospital Universitari Germans Trias i Pujol

Barcelona, , Spain

Site Status

Hospital Universitario de La Princesa

Madrid, , Spain

Site Status

Hospital Universitario Puerta de Hierro

Madrid, , Spain

Site Status

Hospital Universitario Nuestra Señora de Valme

Seville, , Spain

Site Status

Countries

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Belgium France Germany Italy Poland Romania Spain

References

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Paeshuyse J, Kaul A, De Clercq E, Rosenwirth B, Dumont JM, Scalfaro P, Bartenschlager R, Neyts J. The non-immunosuppressive cyclosporin DEBIO-025 is a potent inhibitor of hepatitis C virus replication in vitro. Hepatology. 2006 Apr;43(4):761-70. doi: 10.1002/hep.21102.

Reference Type BACKGROUND
PMID: 16557546 (View on PubMed)

Inoue K, Umehara T, Ruegg UT, Yasui F, Watanabe T, Yasuda H, Dumont JM, Scalfaro P, Yoshiba M, Kohara M. Evaluation of a cyclophilin inhibitor in hepatitis C virus-infected chimeric mice in vivo. Hepatology. 2007 Apr;45(4):921-8. doi: 10.1002/hep.21587.

Reference Type BACKGROUND
PMID: 17393519 (View on PubMed)

Flisiak R, Horban A, Gallay P, Bobardt M, Selvarajah S, Wiercinska-Drapalo A, Siwak E, Cielniak I, Higersberger J, Kierkus J, Aeschlimann C, Grosgurin P, Nicolas-Metral V, Dumont JM, Porchet H, Crabbe R, Scalfaro P. The cyclophilin inhibitor Debio-025 shows potent anti-hepatitis C effect in patients coinfected with hepatitis C and human immunodeficiency virus. Hepatology. 2008 Mar;47(3):817-26. doi: 10.1002/hep.22131.

Reference Type BACKGROUND
PMID: 18302285 (View on PubMed)

Reesink HW, Zeuzem S, Weegink CJ, Forestier N, van Vliet A, van de Wetering de Rooij J, McNair L, Purdy S, Kauffman R, Alam J, Jansen PL. Rapid decline of viral RNA in hepatitis C patients treated with VX-950: a phase Ib, placebo-controlled, randomized study. Gastroenterology. 2006 Oct;131(4):997-1002. doi: 10.1053/j.gastro.2006.07.013.

Reference Type BACKGROUND
PMID: 17030169 (View on PubMed)

Pawlotsky JM. Treatment of hepatitis C: don't put all your eggs in one basket! Gastroenterology. 2007 Apr;132(4):1611-5. doi: 10.1053/j.gastro.2007.03.014. No abstract available.

Reference Type BACKGROUND
PMID: 17418174 (View on PubMed)

Dienstag JL, McHutchison JG. American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology. 2006 Jan;130(1):231-64; quiz 214-7. doi: 10.1053/j.gastro.2005.11.010. No abstract available.

Reference Type BACKGROUND
PMID: 16401486 (View on PubMed)

Zeuzem S, Buti M, Ferenci P, Sperl J, Horsmans Y, Cianciara J, Ibranyi E, Weiland O, Noviello S, Brass C, Albrecht J. Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia. J Hepatol. 2006 Jan;44(1):97-103. doi: 10.1016/j.jhep.2005.10.003. Epub 2005 Nov 7.

Reference Type BACKGROUND
PMID: 16290907 (View on PubMed)

Watashi K, Hijikata M, Hosaka M, Yamaji M, Shimotohno K. Cyclosporin A suppresses replication of hepatitis C virus genome in cultured hepatocytes. Hepatology. 2003 Nov;38(5):1282-8. doi: 10.1053/jhep.2003.50449.

Reference Type BACKGROUND
PMID: 14578868 (View on PubMed)

Watashi K, Ishii N, Hijikata M, Inoue D, Murata T, Miyanari Y, Shimotohno K. Cyclophilin B is a functional regulator of hepatitis C virus RNA polymerase. Mol Cell. 2005 Jul 1;19(1):111-22. doi: 10.1016/j.molcel.2005.05.014.

Reference Type BACKGROUND
PMID: 15989969 (View on PubMed)

Rice CM, You S. Treating hepatitis C: can you teach old dogs new tricks? Hepatology. 2005 Dec;42(6):1455-8. doi: 10.1002/hep.20975.

Reference Type BACKGROUND
PMID: 16317665 (View on PubMed)

Ishii N, Watashi K, Hishiki T, Goto K, Inoue D, Hijikata M, Wakita T, Kato N, Shimotohno K. Diverse effects of cyclosporine on hepatitis C virus strain replication. J Virol. 2006 May;80(9):4510-20. doi: 10.1128/JVI.80.9.4510-4520.2006.

Reference Type BACKGROUND
PMID: 16611911 (View on PubMed)

Yang F, Robotham JM, Nelson HB, Irsigler A, Kenworthy R, Tang H. Cyclophilin A is an essential cofactor for hepatitis C virus infection and the principal mediator of cyclosporine resistance in vitro. J Virol. 2008 Jun;82(11):5269-78. doi: 10.1128/JVI.02614-07. Epub 2008 Apr 2.

Reference Type BACKGROUND
PMID: 18385230 (View on PubMed)

Related Links

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Other Identifiers

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2008-004605-34

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CDEB025A2205

Identifier Type: OTHER

Identifier Source: secondary_id

Debio 025-HCV-205

Identifier Type: -

Identifier Source: org_study_id

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