A study to find out the how your body reacts, absorbs, metabolizes and eliminates a combination of drugs and their ability to reduce the activity of a virus that causes permanent inflammation of the liver (Hepatitis C virus).

• Register: EUCTR
• Last refreshed on: 27 January 2014
• Main ID: EUCTR2011-004129-28-SK
• Date of registration: 06/12/2011
• Prospective Registration: Yes
• Primary sponsor: F. Hoffmann-La Roche
• Public title: A study to find out the how your body reacts, absorbs, metabolizes and eliminates a combination of drugs and their ability to reduce the activity of a virus that causes permanent inflammation of the liver (Hepatitis C virus).
• Scientific title: Study To Evaluate Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Ritonavir-Boosted DANOPREVIR in Combination With Peginterferon Alfa-2a Plus Ribavirin in Treatment-naive Patients and with addition of RO5024048 in Previous Null Responder Patients With Chronic Hepatitis C Genotype 1 or 4 and Compensated Cirrhosis.
• Date of first enrolment: 24/01/2012
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004129-28
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Australia, Canada, France, New Zealand, Poland, Slovakia, United States

Contacts

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

• Name: Trial Information Support Line-TISL
• Affiliation: F. Hoffmann-La Roche Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
• Gender : Male and Female
• History of CHC GT 1 or GT 4, documented with HCV genotype and serum HCV RNA of > 1 x 105 IU/mL at Screening.
• HCV-treatment-naive Cohort 1 (ie, have never received treatment for their condition including but not limited to IFN-based therapy, RBV, or other anti-viral agents with established or perceived activity against HCV).
• HCV prior P/R null responders for Cohort 2. Documentation of previous treatment failure after starting treatment with approved doses of PEG-IFN plus RBV. Patients must have been adherent to previous therapy and have taken a minimum of approximately 80% of the previous course of therapy for a least the first 12 weeks as estimated by the investigator in consultation with the patients and must have failed treatment as a consequence of null virologic response (<2 log 10 reduction in HCV RNA at week 12).
• Liver biopsy confirming cirrhosis: Knodell score = 4, Metavir score = 4, Batts & Ludwig score = 4, or Ishak modified HAI score = 5
• Compensated cirrhosis (Child-Pugh A)
• Patients must have an abdominal ultrasound, computerized tomography (CT) scan, or magnetic resonance imaging (MRI) scan without evidence of hepatocellular carcinoma (within 6 months prior to Screening), and a serum alfa-fetoprotein (AFP) <100ng/mL (< 100 µg/L at Screening).

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion criteria:
• History or presence of decompensated liver disease (history of ascites, hepatic encephalopathy, hepatocellular carcinoma, or bleeding esophageal varices).
• For Cohort 2: Patients who discontinued previous P/R therapy due to reasons other than null response (eg, intolerability, lost to follow up, noncompliance).
• Presence or history of non-hepatitis C chronic liver disease, including but not limited to, autoimmune hepatitis, alfa-1-antitrypsin deficiency, C282Y homozygous hemochromatosis, Wilson’s disease, drug- or toxin-induced liver disease, alcohol-related liver disease, primary biliary cirrhosis, sclerosing cholangitis, and porphyria cutanea tarda causing liver pathology or requiring phlebotomy.
• Positive Hepatitis B surface antigen (HBsAg) or human immunodeficiency virus (HIV) antibody at Screening.
• Use of blood transfusion growth factors (including, but not limited to, granulocyte colony stimulating factor or erythropoietin) or any other therapeutic agents to elevate hematology parameters to facilitate patient entry into the study within 3 months before Screening
• History of severe psychiatric disease
• Laboratory parameters: ALT > 10x ULN; Bi =1.5x ULN; serum amylase or lipase > 1.5 x ULN; Hgb < 12- g/L (males), < 120 g/L (females): HA1c =8.5;CrCl < 70 mL/min, microproteinuria and Uprotein/Cr ratio = 0.3 (33.89 mg/mmoL; ANC = 1500 /µL; platelets = 90,000/µL



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Chronic Hepatitis C
MedDRA version: 14.0 Level: LLT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Product Name: Danoprevir
Product Code: RO5190591/F24
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Danoprevir
Current Sponsor code: RO5190591
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Trade Name: Norvir
Product Code: Ro0326047
Pharmaceutical Form: Tablet
INN or Proposed INN: RITONAVIR
CAS Number: 155213-67-5
Current Sponsor code: RO0326047
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-

Product Name: RO5024048
Product Code: RO5024048/F14
Pharmaceutical Form: Film-coated tablet
Current Sponsor code: RO5024048
Other descriptive name: HCV Polymerase Inhibitor Prodrug
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 500-

Primary Outcome(s)

Primary end point(s): safety, tolerability, pharmacokinetics (PK) and antiviral activity

Main Objective: safety, tolerability, pharmacokinetics (PK) and antiviral activity of RO5190591/ritonavir (danoprevir/r) in combination with peginterferon and ribavirin in treatment-naïve genotype 1 or 4 chronic hepatitis C patients with compensated cirrhosis and danoprevir/r +RO5024048 in combination with peginterferon and ribavirin in null responder genotype 1 or 4 chronic hepatitis C patients with compensated cirrhosis

Secondary Objective: characterize the emergence of danoprevir (DNV) and/or RO5024048 resistance.
evaluate Rapid Virological Response (RVR), complete Early Virological Response (cEVR), and Sustained Virological Response (SVR) in each cohort

Timepoint(s) of evaluation of this end point: Study visits to assess safety, tolerability, PK and antiviral activity (PD) are scheduled at the following time points:
Screening (day-56 to day-36), rescreening (day -35 to day -2if necessary), Day -1, Day 1, 2, 3, 6, 8, 12, 13, 14, 15, then every 2 weeks during treatment (wk 4, 6, 8, 10, 1 2, 14, 16, 18, 20, 22, 24)At three off-treatment follow-up visits: at 4, 12 and 24 weeks following end of treatment

Secondary Outcome(s)

Secondary end point(s): -Development of resistant mutations to danoprevir (DNV) and/or RO5024048 treatment
-Rapid Virological Response (RVR), complete Early Virological Response (cEVR), and Sustained Virological Response (SVR) in each cohort

Timepoint(s) of evaluation of this end point: RVR at study week 4, cEVR at study week 24, SVR at 24 weeks post end of treatment

Secondary ID(s)

NP27946

Source(s) of Monetary Support

F. Hoffmann-La Roche AG