A Randomized, Double-blinded, Multicenter, Dose and Duration Finding Study to Evaluate the Sustained Virologic Response of the HCV Polymerase Inhibitor Prodrug (RO5024048) in Combination with Pegasys® and Copegus® versus the Currently Approved Combination of Pegasys® and Copegus® in Treatment-Naive Patients with Chronic Hepatitis C Genotype 1 or 4 Virus Infection.
- Conditions
- Chronic Hepatitis CMedDRA version: 9.1Level: LLTClassification code 10008912Term: Chronic hepatitis C
- Registration Number
- EUCTR2008-008258-21-AT
- Lead Sponsor
- F. Hoffmann-La Roche Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 400
1.Age 18 – 65 years
2.Serologic evidence of CHC infection by an anti-HCV antibody test (current or historical)
3.Evidence of chronic hepatitis C infection > 6 months duration
4.Evidence of hepatitis C genotype 1 or 4 infection by molecular assay
5.Serum HCV RNA quantifiable at =50,000 IU/mL as demonstrated by the Roche COBAS TaqMan HCV Test
6.Chronic liver disease consistent with chronic hepatitis C infection on a biopsy obtained within the past 24 months (36 months for patients with cirrhosis or incomplete/transition to cirrhosis), using one of the scoring methods in Appendix 2
7.Patients with cirrhosis or incomplete/transition to cirrhosis must have an abdominal ultrasound, computerized tomography (CT) scan, or magnetic resonance imaging (MRI) scan without evidence of hepatocellular carcinoma (within 2 months prior to randomization) and a serum alpha-fetoprotein (AFP) < 100 ng/mL (< 100 µg/L)
8.Compensated liver disease (Child-Pugh Grade A clinical classification only)
9.Negative urine pregnancy test (for females of childbearing potential) documented within the 24-hour period prior to the first dose of study drugs confirmed by negative serum pregnancy test collected within 24 hours prior to the first dose of study drug. Additionally, all female patients of childbearing potential and all males with female partners of childbearing potential must use two forms of effective contraception (combined) during treatment and following the last dose of RBV in accordance with locally approved label for RBV
10.Willingness to give written informed consent and willingness to participate in and comply with the study requirements
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
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1.Females who are pregnant or breast feeding
2.Male partners of females who are pregnant
3.Body mass index (BMI) < 18 or = 36
4.Infection with any HCV genotype other than genotype 1 or 4. Genotype 1 and 4 patients with indeterminate or mixed subtypes will be allowed
5.History of having received any IFN, PEG-IFN, RBV, viramidine, levovirin, polymerase or protease inhibitors or other investigational anti-HCV at any time, or any other systemic antiviral therapy with established or perceived activity against the hepatitis C virus = 3 months prior to the first dose of study drug
6.History of having received any investigational drug = 3 months prior to the first dose of study drug or the expectation that such drugs will be used during the study. Patients enrolled in this study cannot be enrolled in another study for either research, diagnostic or treatment purposes
7.Patients who are expected to need systemic antiviral therapy with established or perceived activity against HCV at any time during their participation in the study
8.Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, or anti HIV Ab
9.History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, Wilson’s disease, a1 antitrypsin deficiency, metabolic liver disease, alcoholic liver disease, and/or toxin exposure)
10.Absolute neutrophil count (ANC) < 1.5 x103 /µL (< 1.5 x 109/L)
11.Platelet count < 90 x103/µL (< 90 x 109/L)
12.Hemoglobin concentration < 12 g/dL (120 g/L) in females or < 13 g/dL (130 g/L) in males or any patient with a baseline increased risk for anemia (e.g., thalassemia, sickle cell anemia, spherocytosis, history of gastrointestinal bleeding) or for whom anemia would be medically problematic
13.Presence of schistocytes on peripheral blood smear
14.Serum amylase or lipase levels > 1.5 times the upper limit of normal
15.Serum total bilirubin = 2 times the upper limit of normal
16.History of pre-existing renal disease. Patients with a history of nephrolithiasis will
be allowed.
17.Estimated creatinine clearance of = 80 mL/min (= 1.34 mL/sec), calculated by the Cockcroft-Gault formula
18.Serum creatinine > 1.5 times the upper limit of normal
19.Greater than trace hematuria (=1+ or >10 RBC/HPF, unless related to menstruation)
20.Microproteinuria with protein/creatinine ratio = 0.3 (= 33.89 mg/mmol) as
determined by urine chemistry test (see Appendix 6 for details)
21. One or more of the following: (i) poorly controlled hypertension, OR (ii) poor
adherence to antihypertensive therapy, OR (iii) current use of > 2 antihypertensive agents required, OR (iv) screening or baseline blood pressure =140 mmHg for systolic OR (v) = 90 mmHg for diastolic blood pressure
22.The use of colony stimulating factors such as granulocyte colony stimulating factor (G-CSF), erythropoietin, blood transfusion or other therapeutic agents to elevate hematology parameters to facilitate patient entry into the study within the last 6 months
23.History of severe psychiatric disease, including psychosis and/or depression, characterized by a suicide attempt, hospitalization for psychiatric disease, or a period of disability as a result of psychiatric disease
24.History of immunologically mediated disease (e.g., vasculitis, cryoglobulinemia, inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis (d
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method