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

Sponsor

Debiopharm International SA (Industry)

Overall Status

Completed

CT.gov ID

NCT00854802

Collaborator

Parexel (Industry)

290

Enrollment

Locations

Arms

Duration (Months)

7.3

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: Debio 025 Drug: Peg-IFNα2a Drug: Ribavirin Drug: Debio 025 placebo	N/A

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

290 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, 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

Study Start Date :

Jan 1, 2009

Actual Primary Completion Date :

Sep 1, 2010

Actual Study Completion Date :

Sep 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Drug: Debio 025 Debio 025 supplied in soft gel capsules Other Names: Alisporivir Drug: Peg-IFNα2a Peg-IFNα2a supplied in pre-filled syringes Other Names: Pegasys Drug: Ribavirin Ribavirin supplied in tablets Other Names: Copegus Rebetol Ribasphere Vilona Virazole
Experimental: 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.	Drug: Debio 025 Debio 025 supplied in soft gel capsules Other Names: Alisporivir Drug: Peg-IFNα2a Peg-IFNα2a supplied in pre-filled syringes Other Names: Pegasys Drug: Ribavirin Ribavirin supplied in tablets Other Names: Copegus Rebetol Ribasphere Vilona Virazole
Experimental: 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.	Drug: Debio 025 Debio 025 supplied in soft gel capsules Other Names: Alisporivir Drug: Peg-IFNα2a Peg-IFNα2a supplied in pre-filled syringes Other Names: Pegasys Drug: Ribavirin Ribavirin supplied in tablets Other Names: Copegus Rebetol Ribasphere Vilona Virazole
Placebo Comparator: 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.	Drug: Peg-IFNα2a Peg-IFNα2a supplied in pre-filled syringes Other Names: Pegasys Drug: Ribavirin Ribavirin supplied in tablets Other Names: Copegus Rebetol Ribasphere Vilona Virazole Drug: Debio 025 placebo Debio 025 placebo supplied in soft gel capsules

Outcome Measures

Primary Outcome Measures

Percentage of participants achieving sustained viral response (SVR) 72 weeks after treatment start [72 weeks after treatment start]
SVR is defined as hepatitis C virus (HCV) RNA < 10 IU/mL (undetectable).

Secondary Outcome Measures

Percentage of participants achieving a rapid viral response (RVR) after 4 weeks of treatment [4 weeks after treatment start]
RVR is defined as HCV RNA level < 10 IU/mL after 4 weeks of treatment.
Percentage of participants achieving a complete early viral response (cEVR) after 12 weeks of treatment [12 weeks after treatment start]
cEVR is defined as HCV RNA level < 10 IU/mL after 12 weeks of treatment.
Percentage of participants achieving an early viral response (EVR) after 12 weeks of treatment [12 weeks after treatment start]
EVR is defined as a decrease from baseline of the HCV RNA level by > 2 log10 or undetectable (< 10 UI/mL) after 12 weeks of treatment.
Percentage of participants achieving an end-of-treatment response (ETR) at treatment end [at end of treatment (Week 28 or Week 52)]
ETR is defined as HCV RNA level < 10 IU/mL at the end of treatment (Week 24 or Week 48).
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)]
SVR 12 is defined as HCV RNA level < 10 IU/mL 12 weeks after the end of treatment (Week 40 or Week 64).
Percentage of participants with sustained viral response 24 weeks after the end of treatment (SVR 24) [24 weeks after end of treatment (Week 52 or Week 76]
SVR 24 is defined as HCV RNA level < 10 IU/mL 24 weeks after the end of treatment (Week 52 or Week 76).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Cliniques Universitaires Saint-Luc	Brussels	Belgium	1200
2	UZ Gent	Gent	Belgium	9000
3	C.H.U - Hôpital Henri-Mondor	Creteil	France	94010
4	C.H.U de Lyon Hôpital de l'Hôtel Dieu	Lyon	France	69288
5	Hôpital de l'Archet 2	Nice	France	06202
6	C.H.U - Hôpital Saint Antoine	Paris - Saint Antoine	France	75571
7	C.H.U Hôpital Cochin	Paris	France	75679
8	Hôpital du Haut-Levêque - C.H.U de Bordeaux	Pessac	France	33604
9	C.H.U de Nancy-Hôpital Brabois	Vandoeuvre-les-Nancy	France	54511
10	Charité - Universitatsmedizin Berlin	Berlin	Germany	13353
11	Universitätsklinikum Düsseldorf	Düsseldorf	Germany	40225
12	Center for HIV and Hepatogastroenterology	Düsseldorf	Germany	40237
13	Universitätsklinikum Essen	Essen	Germany	45122
14	J.W. Goethe University Hospital	Frankfurt am Main	Germany	60590
15	Albert-Ludwigs-Universität Freiburg, Universitätsk	Freiburg	Germany	79106
16	Medizinische Hochschule Hannover	Hannover	Germany	30623
17	Medizinische Universitätsklinik	Heidelberg	Germany	69120
18	Johannes Gutenberg-Universitaet Mainz	Mainz	Germany	55101
19	Policlinico S.Orsola Malpighi	Bologna	Italy	40138
20	Mangiagalli e Regina Elena di Milano	Milano	Italy	20122
21	Seconda Università di Napoli- Secondo Policlinico	Napoli	Italy	80131
22	"Policlinico ""Paolo Giaccone"" dell'Università di	Palermo	Italy	90127
23	Az. Osp. Universitaria S. Giovanni Battista	Torino	Italy	10126
24	Wojewódzki Szpital Specjalistyczny im. K. Dluskieg	Bialystok	Poland	15-540
25	Wojewódzki Szpital Obserwacyjno-Zakazny im. Tadeus	Bydgoszcz	Poland	85-030
26	Szpital Specjalistyczny w Chorzowie	Chorzów	Poland	41-500
27	Wojewódzki Szpital Zespolony w Kielcach	Kielce	Poland	25-736
28	Krakowski Szpital Specjalistyczny im. Jana Pawla I	Krakow	Poland	31-202
29	Wojewódzki Szpital Specjalstyczny im. Wl. Biegansk	Lódz	Poland	91-347
30	Samodzielny Publiczny Zaklad Opieki Zdrowotnej Woj	Warszawa	Poland	01-201
31	Spitalul Clinic Colentina	Bucharest	Romania	20125
32	Institutul Clinic Fundeni	Bucharest	Romania	22328
33	Centrul de Diagnostic si Tratament Dr. Victor Babe	Bucharest	Romania	30303
34	"Spitalul Clinic de Urgenta ""Prof. dr. Octavian F	Cluj Napoca	Romania	400162
35	Institutul de Gastroenterologie si Hepatologie	Iasi	Romania	700111
36	Hospital Universitari Vall d'Hebrón	Barcelona	Spain	8035
37	Hospital Universitari Germans Trias i Pujol	Barcelona	Spain	8916
38	Hospital Universitario de La Princesa	Madrid	Spain	28006
39	Hospital Universitario Puerta de Hierro	Madrid	Spain	28035
40	Hospital Universitario Nuestra Señora de Valme	Sevilla	Spain	41014