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

This study has been completed.
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Debiopharm International SA
ClinicalTrials.gov Identifier:
NCT00854802
First received: March 2, 2009
Last updated: August 7, 2012
Last verified: August 2012
  Purpose

The purpose of this study is to compare several Debio025/peg IFNalpha2a/ribavirin triple therapies with the current standard of care (SOC) in treatment naïve chronic hepatitis C genotype 1 patients.


Condition Intervention Phase
Chronic Hepatitis C
Drug: Debio 025
Drug: Debio 025 placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicentre, Randomised, Double-blind, Placebo-controlled, Parallel-group Phase II Study on the Efficacy and Safety of Debio 025 Combined With Peg-IFNα2a and Ribavirin in Treatment naïve Chronic Hepatitis C Genotype 1 Patients

Resource links provided by NLM:


Further study details as provided by Debiopharm International SA:

Primary Outcome Measures:
  • Proportion of patients achieving SVR 24 [ Time Frame: HCV RNA < 10 IU/mL 72 weeks after treatment start ] [ Designated as safety issue: Yes ]
    in each treatment arm, proportion of patients who develop a mutant viral strain selecting for resistance against treatment regimens, proportion of patients with abnormal ALAT at baseline who normalise ALAT levels at treatment end, safety parameters and drug pharmacokinetics


Secondary Outcome Measures:
  • Proportion of patients achieving RVR [ Time Frame: HCV RNA < 10 IU/mL after 4 weeks of treatment ] [ Designated as safety issue: Yes ]
    in each treatment arm, proportion of patients who develop a mutant viral strain selecting for resistance against treatment regimens, proportion of patients with abnormal ALAT at baseline who normalise ALAT levels at treatment end, safety parameters and drug pharmacokinetics

  • cEVR [ Time Frame: HCV RNA < 10 IU/mL after 12 weeks of treatment ] [ Designated as safety issue: Yes ]
    in each treatment arm, proportion of patients who develop a mutant viral strain selecting for resistance against treatment regimens, proportion of patients with abnormal ALAT at baseline who normalise ALAT levels at treatment end, safety parameters and drug pharmacokinetics

  • EVR [ Time Frame: HCV RNA decrease by > 2 log10 or undetectable [< 10 IU/mL] after 12 weeks of treatment ] [ Designated as safety issue: Yes ]
    in each treatment arm, proportion of patients who develop a mutant viral strain selecting for resistance against treatment regimens, proportion of patients with abnormal ALAT at baseline who normalise ALAT levels at treatment end, safety parameters and drug pharmacokinetics

  • ETR [ Time Frame: HCV RNA < 10 IU/mL at treatment end ] [ Designated as safety issue: Yes ]
    in each treatment arm, proportion of patients who develop a mutant viral strain selecting for resistance against treatment regimens, proportion of patients with abnormal ALAT at baseline who normalise ALAT levels at treatment end, safety parameters and drug pharmacokinetics

  • SVR 12 [ Time Frame: HCV RNA < 10 IU/mL 12 weeks after treatment end ] [ Designated as safety issue: Yes ]
    in each treatment arm, proportion of patients who develop a mutant viral strain selecting for resistance against treatment regimens, proportion of patients with abnormal ALAT at baseline who normalise ALAT levels at treatment end, safety parameters and drug pharmacokinetics

  • SVR 24 [ Time Frame: HCV RNA > 10 IU/mL 24 weeks after treatment end ] [ Designated as safety issue: Yes ]
    in each treatment arm, proportion of patients who develop a mutant viral strain selecting for resistance against treatment regimens, proportion of patients with abnormal ALAT at baseline who normalise ALAT levels at treatment end, safety parameters and drug pharmacokinetics


Enrollment: 290
Study Start Date: December 2008
Study Completion Date: September 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
48 weeks, Peg-IFN Alpha-2a/Ribavirin/Debio 025 600 mg
Drug: Debio 025
Patients in experimental treatment arm 1 will receive Debio 025 orally twice daily for 7 days (loading dose) followed by 600 mg orally once daily for 47 weeks in combination with Peg-IFNalpha2a 180 µg s.c. once weekly and ribavirin 1000 or 1200 mg orally daily (weight based)for 48 weeks.
Experimental: 2
24 weeks, Peg-IFN Alpha-2a/Ribavirin/Debio 025 600 mg
Drug: Debio 025
Patients in experimental treatment arm 2 will receive Debio 025 orally twice daily for 7 days (loading dose) followed by 600 mg orally once daily for 23 weeks in combination with Peg-IFNalpha2a 180 µg s.c. once weekly and ribavirin 1000 or 1200 mg orally daily (weight based) for 24 weeks.
Experimental: 3
24 or 48 weeks (response-guided), Peg-IFN Alpha-2a/Ribavirin/Debio 025 600 mg Placebo comparator
Drug: Debio 025
Patients in experimental treatment arm 3 will receive Debio 025 orally twice daily for 7 days (loading dose) followed by 600 mg orally once daily for 23 weeks or 47 weeks in combination with Peg-IFNalpha2a 180 µg s.c. once weekly and ribavirin 1000 or 1200 mg orally daily (weight based) for 24 weeks or 48 weeks.
Experimental: 4
48 weeks, Peg-IFN Alpha-2a/Ribavirin/Debio 025 placebo
Drug: Debio 025 placebo
Patients in Debio 025 placebo arm will receive 3 soft gel placebo capsules twice daily for 7 days followed by 3 soft gel placebo capsules once daily for 47 weeks.

Detailed Description:

This is an international, multicentre, randomised, double-blind, placebo-controlled, 4-arm parallel-group multiple dose phase II study comparing three Debio 025/peg IFNa2a/ribavirin regimens to SOC treatment in 272 treatment naïve chronic HCV genotype 1 patients.

Patients will be randomised into one of 4 arms receiving either Debio 025/peg IFNalpha2a/ribavirin triple therapy for a fixed treatment duration of 48 (Treatment A) or 24 (Treatment B) weeks, or Debio 025/peg IFNalpha2a/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 will last 24 weeks in all treatment arms.

In 48-week treatment arms (Treatments A, C, and D), the entire study will last a maximum of 76 weeks, including a screening period of about 4 weeks, a 48-week treatment period and a 24-week follow up period. In 24-week treatment arms (Treatment B and C), the entire study will last a maximum of 52 weeks, including a screening period of about 4 weeks, a 24-week treatment period and a 24-week follow up period.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males or females aged ≥18 and ≤65 years;
  • BMI between ≥18 and ≤ 32 kg/m2;
  • 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 HCV infection (approved or investigational drug);
  • Plasma HCV RNA level lower limit ≥100 IU/ml assessed by qPCR or equivalent; no upper limit;
  • Neutrophil count ≥1500/µL; 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
  • ASAT and ALAT < 5 times the upper limit of normal;
  • Normal or compensated liver function and absence of complicated portal hypertension as documented by the following:

    1. No history of bleeding oesophageal varices;
    2. Absence of ascites;
    3. Absence of encephalopathy;
    4. Albumin ≥ 35 g/L;
    5. Total bilirubin ≤ 1.8 mg/dL (≤ 30µmol/L);
    6. Prothrombin (INR ≤ 1.5);
  • Creatinine clearance > 50 mL/min;
  • TSH within normal range;
  • All patients should be advised on Debio 025 and ribavirin foetotoxicity:

    1. 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.
    2. 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 CYP450 3A, substrates of P-gP, or substrates/inhibitors of OATPs, MRP2, or 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 HBV, drug- or alcohol-related cirrhosis, autoimmune hepatitis, haemochromatosis, Wilson's disease, NASH, PSC, or PBC;
  • Any other condition which, in the opinion of the Investigator, would make the patient unsuitable for enrolment 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, i.e. patients with systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg;
  • History of pancreatitis, uncontrolled diabetes mellitus or retinopathy;
  • 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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00854802

  Hide Study Locations
Locations
Belgium
Cliniques Universitaires Saint-Luc
Brussels, Belgium, 1200
UZ Gent
Gent, Belgium, 9000
France
C.H.U - Hôpital Henri-Mondor
Creteil, France, 94010
C.H.U de Lyon Hôpital de l'Hôtel Dieu
Lyon, France, 69288
Hôpital de l'Archet 2
Nice, France, 06202
C.H.U Hôpital Cochin
Paris, France, 75679
C.H.U - Hôpital Saint Antoine
Paris - Saint Antoine, France, 75571
Hôpital du Haut-Levêque - C.H.U de Bordeaux
Pessac, France, 33604
C.H.U de Nancy-Hôpital Brabois
Vandoeuvre-les-Nancy, France, 54511
Germany
Charité - Universitatsmedizin Berlin
Berlin, Germany, 13353
Center for HIV and Hepatogastroenterology
Düsseldorf, Germany, 40237
Universitätsklinikum Düsseldorf
Düsseldorf, Germany, 40225
Universitätsklinikum Essen
Essen, Germany, 45122
J.W. Goethe University Hospital
Frankfurt am Main, Germany, 60590
Albert-Ludwigs-Universität Freiburg, Universitätsk
Freiburg, Germany, 79106
Medizinische Hochschule Hannover
Hannover, Germany, 30623
Medizinische Universitätsklinik
Heidelberg, Germany, 69120
Johannes Gutenberg-Universitaet Mainz
Mainz, Germany, 55101
Italy
Policlinico S.Orsola Malpighi
Bologna, Italy, 40138
Mangiagalli e Regina Elena di Milano
Milano, Italy, 20122
Seconda Università di Napoli- Secondo Policlinico
Napoli, Italy, 80131
"Policlinico ""Paolo Giaccone"" dell'Università di
Palermo, Italy, 90127
Az. Osp. Universitaria S. Giovanni Battista
Torino, Italy, 10126
Poland
Wojewódzki Szpital Specjalistyczny im. K. Dluskieg
Bialystok, Poland, 15-540
Wojewódzki Szpital Obserwacyjno-Zakazny im. Tadeus
Bydgoszcz, Poland, 85-030
Szpital Specjalistyczny w Chorzowie
Chorzów, Poland, 41-500
Wojewódzki Szpital Zespolony w Kielcach
Kielce, Poland, 25-736
Krakowski Szpital Specjalistyczny im. Jana Pawla I
Krakow, Poland, 31-202
Wojewódzki Szpital Specjalstyczny im. Wl. Biegansk
Lódz, Poland, 91-347
Samodzielny Publiczny Zaklad Opieki Zdrowotnej Woj
Warszawa, Poland, 01-201
Romania
Institutul Clinic Fundeni
Bucharest, Romania, 22328
Spitalul Clinic Colentina
Bucharest, Romania, 20125
Centrul de Diagnostic si Tratament Dr. Victor Babe
Bucharest, Romania, 30303
"Spitalul Clinic de Urgenta ""Prof. dr. Octavian F
Cluj Napoca, Romania, 400162
Institutul de Gastroenterologie si Hepatologie
Iasi, Romania, 700111
Spain
Hospital Universitari Germans Trias i Pujol
Barcelona, Spain, 8916
Hospital Universitari Vall d'Hebrón
Barcelona, Spain, 8035
Hospital Universitario Puerta de Hierro
Madrid, Spain, 28035
Hospital Universitario de La Princesa
Madrid, Spain, 28006
Hospital Universitario Nuestra Señora de Valme
Sevilla, Spain, 41014
Sponsors and Collaborators
Debiopharm International SA
Parexel
Investigators
Study Director: Rafael Crabbé, M.D. Debiopharm SA
  More Information

Additional Information:
Publications:

Responsible Party: Debiopharm International SA
ClinicalTrials.gov Identifier: NCT00854802     History of Changes
Other Study ID Numbers: Debio 025-HCV-205, EudraCT n° 2008-004605-34
Study First Received: March 2, 2009
Last Updated: August 7, 2012
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Federal Institute for Drugs and Medical Devices
Italy: The Italian Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Romania: National Medicines Agency
Spain: Spanish Agency of Medicines

Keywords provided by Debiopharm International SA:
Hepatitis, Hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Interferon-alpha
Ribavirin
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 16, 2014