| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Hepatitis C (CHC). |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10019744 |
| E.1.2 | Term | Hepatitis C |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
- To determine the optimal treatment combination based on the efficacy and safety of the HCV Polymerase Inhibitor Prodrug (RO4588161) 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 virus infection. |
|
| E.2.2 | Secondary objectives of the trial |
- To evaluate and compare the exposure levels of RO1048297 (parent compound of RO4588161) in combination with
Pegasys and Copegus
- To evaluate the resistance profile of RO4588161 in combination with Pegasys and Copegus |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Age 18 – 65 years
2. Serologic evidence of CHC infection by an anti-HCV antibody test (current or historical)
3. Evidence of hepatitis C genotype 1 infection by molecular assay
4. Serum HCV RNA quantifiable at > 10,000 IU/mL as demonstrated by the Roche COBAS TaqMan HCV Test
5. 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 proposed scoring methods.
6. Patients with cirrhosis or incomplete/transition to cirrhosis must have an abdominal ultrasound, computerized tomographic (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
7. Compensated liver disease (Child-Pugh Grade A clinical classification only)
8. Negative serum pregnancy test (for females of childbearing potential)
documented within the 24-hour period prior to the first dose of study drugs.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 for 6 months after treatment end
9. Willingness to give written informed consent and willingness to participate in and comply with the study requirements |
|
| E.4 | Principal exclusion criteria |
1. Infection with any HCV genotype other than genotype 1 or an indeterminate or mixed genotype. Genotype 1 patients with indeterminate or mixed subtypes will be allowed
2. History of having received any IFN, PEG-IFN, RBV, viramidine, levovirin, or
investigational HCV polymerase or protease inhibitors at any previous 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
3. 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
4. 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 are also excluded
5. Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, or
anti-HIV Ab
6. History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
7. Females who are pregnant or breast feeding
8. Male partners of females who are pregnant
9. Body mass index (BMI) > 36 or < 18
10. Absolute neutrophil count (ANC) < 2000 cells/mm3
11. Platelet count <90,000 cells/mm3
12. Hemoglobin concentration < 12 g/dL in females or <13 g/dL 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. Serum creatinine level > 1.5 times the upper limit of normal at screening
14. The use of colony stimulating factors such as granulocyte colony stimulating factor (G-CSF), erythropoietin or other therapeutic agents to elevate hematology
parameters to facilitate patient entry into the study
15. 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
16. History of immunologically mediated disease (e.g., inflammatory bowel disease,
idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune
hemolytic anemia, scleroderma, severe psoriasis (defined as affecting > 10% of
the body, where the palm of one hand equals 1%, or if the hands and feet are affected), rheumatoid arthritis requiring more than intermittent nonsteroidal antiinflammatory
medications for management)
17. History or other evidence of decompensated liver disease or a Child-Pugh score >6. Coagulopathy, hyperbilirubinemia, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices are conditions consistent with decompensated liver disease
18. History or other evidence of chronic pulmonary disease associated with functional limitation; Etc... |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Percentage of patients with
undetectable HCV RNA as measured by the Roche COBAS TaqMan HCV Test
(detection limit = 15 IU/mL) 24 weeks after end of treatment. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 9 |
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