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

NCT00854802 | Completed DMC

• 3 other identifiers: Debio 025-HCV-2052008-004605-34CDEB025A2205
• Study Type: interventional
• Target: 290
• Locations: 7 countries
• Sites: 40

Brief Summary

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.

Conditions

Chronic Hepatitis C

Keywords

Hepatitis; Hepatitis C

Outcome Measures

Primary Outcomes (1)

• Percentage of participants achieving sustained viral response (SVR) 72 weeks after treatment start

  SVR is defined as hepatitis C virus (HCV) RNA \< 10 IU/mL (undetectable).

  72 weeks after treatment start

Secondary Outcomes (6)

• Percentage of participants achieving a rapid viral response (RVR) after 4 weeks of treatment

  4 weeks after treatment start

• Percentage of participants achieving a complete early viral response (cEVR) after 12 weeks of treatment

  12 weeks after treatment start

• Percentage of participants achieving an early viral response (EVR) after 12 weeks of treatment

  12 weeks after treatment start

• Percentage of participants achieving an end-of-treatment response (ETR) at treatment end

  at end of treatment (Week 28 or Week 52)

• Percentage of participants achieving a sustained viral response 12 weeks after the end of treatment (SVR 12)

  12 weeks after end of treatment (Week 40 or Week 64)

Study Arms (4)

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

EXPERIMENTAL

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.

Drug: Debio 025; Drug: Peg-IFNα2a; Drug: Ribavirin

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

EXPERIMENTAL

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.

Drug: Debio 025; Drug: Peg-IFNα2a; Drug: Ribavirin

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

EXPERIMENTAL

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.

Drug: Debio 025; Drug: Peg-IFNα2a; Drug: Ribavirin

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

PLACEBO COMPARATOR

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.

Drug: Peg-IFNα2a; Drug: Ribavirin; Drug: Debio 025 placebo

Interventions

Debio 025 DRUG

Debio 025 supplied in soft gel capsules

Also known as: Alisporivir

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

Peg-IFNα2a DRUG

Peg-IFNα2a supplied in pre-filled syringes

Also known as: Pegasys

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

Ribavirin DRUG

Ribavirin supplied in tablets

Also known as: Copegus, Rebetol, Ribasphere, Vilona, Virazole

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

Debio 025 placebo DRUG

Debio 025 placebo supplied in soft gel capsules

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

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Debiopharm International SA: lead
• Parexel: collaborator

Study Sites (40)

Cliniques Universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

C.H.U - Hôpital Henri-Mondor

Créteil, 94010, France

Location

C.H.U de Lyon Hôpital de l'Hôtel Dieu

Lyon, 69288, France

Location

Hôpital de l'Archet 2

Nice, 06202, France

Location

C.H.U Hôpital Cochin

Paris, 75679, France

Location

C.H.U - Hôpital Saint Antoine

Paris - Saint Antoine, 75571, France

Location

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

Pessac, 33604, France

Location

C.H.U de Nancy-Hôpital Brabois

Vandœuvre-lès-Nancy, 54511, France

Location

Charité - Universitatsmedizin Berlin

Berlin, 13353, Germany

Location

Universitätsklinikum Düsseldorf

Düsseldorf, 40225, Germany

Location

Center for HIV and Hepatogastroenterology

Düsseldorf, 40237, Germany

Location

Universitätsklinikum Essen

Essen, 45122, Germany

Location

J.W. Goethe University Hospital

Frankfurt am Main, 60590, Germany

Location

Albert-Ludwigs-Universität Freiburg, Universitätsk

Freiburg im Breisgau, 79106, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30623, Germany

Location

Medizinische Universitätsklinik

Heidelberg, 69120, Germany

Location

Johannes Gutenberg-Universitaet Mainz

Mainz, 55101, Germany

Location

Policlinico S.Orsola Malpighi

Bologna, 40138, Italy

Location

Mangiagalli e Regina Elena di Milano

Milan, 20122, Italy

Location

Seconda Università di Napoli- Secondo Policlinico

Napoli, 80131, Italy

Location

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

Palermo, 90127, Italy

Location

Az. Osp. Universitaria S. Giovanni Battista

Torino, 10126, Italy

Location

Wojewódzki Szpital Specjalistyczny im. K. Dluskieg

Bialystok, 15-540, Poland

Location

Wojewódzki Szpital Obserwacyjno-Zakazny im. Tadeus

Bydgoszcz, 85-030, Poland

Location

Szpital Specjalistyczny w Chorzowie

Chorzów, 41-500, Poland

Location

Wojewódzki Szpital Zespolony w Kielcach

Kielce, 25-736, Poland

Location

Krakowski Szpital Specjalistyczny im. Jana Pawla I

Krakow, 31-202, Poland

Location

Wojewódzki Szpital Specjalstyczny im. Wl. Biegansk

Lódz, 91-347, Poland

Location

Samodzielny Publiczny Zaklad Opieki Zdrowotnej Woj

Warsaw, 01-201, Poland

Location

Spitalul Clinic Colentina

Bucharest, 20125, Romania

Location

Institutul Clinic Fundeni

Bucharest, 22328, Romania

Location

Centrul de Diagnostic si Tratament Dr. Victor Babe

Bucharest, 30303, Romania

Location

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

Cluj-Napoca, 400162, Romania

Location

Institutul de Gastroenterologie si Hepatologie

Iași, 700111, Romania

Location

Hospital Universitari Vall d'Hebrón

Barcelona, 8035, Spain

Location

Hospital Universitari Germans Trias i Pujol

Barcelona, 8916, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital Universitario Puerta de Hierro

Madrid, 28035, Spain

Location

Hospital Universitario Nuestra Señora de Valme

Seville, 41014, Spain

Location

Related Publications (12)

• 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.

  PMID: 16557546 BACKGROUND

• 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.

  PMID: 17393519 BACKGROUND

• 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.

  PMID: 18302285 BACKGROUND

• 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.

  PMID: 17030169 BACKGROUND

• 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.

  PMID: 17418174 BACKGROUND

• 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.

  PMID: 16401486 BACKGROUND

• 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.

  PMID: 16290907 BACKGROUND

• 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.

  PMID: 14578868 BACKGROUND

• 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.

  PMID: 15989969 BACKGROUND

• 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.

  PMID: 16317665 BACKGROUND

• 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.

  PMID: 16611911 BACKGROUND

• 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.

  PMID: 18385230 BACKGROUND

Related Links

• Study sponsor

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis; Hepatitis C

Interventions

alisporivir; peginterferon alfa-2a; Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Rafael Crabbé, MD

  Debiopharm International SA

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2009
• First Posted: March 3, 2009
• Study Start: January 1, 2009
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: February 17, 2016

Record last verified: 2016-02

Locations

ES (5); PL (7); BE (2); FR (7); DE (9); IT (5); RO (5)