E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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 | 10008912 |
E.1.2 | Term | Chronic hepatitis C |
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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 |
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E.2.2 | Secondary objectives of the trial |
- To evaluate the pharmacokinetics of RO1048297 (parent compound of RO4588161) when administering RO4588161 in combination with Pegasys and Copegus - To evaluate the resistance profile of RO4588161 in combination with Pegasys and Copegus
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E.2.3 | Trial contains a sub-study | No |
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 ≥ 50,000 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 scoring methods in Appendix 2 of the protocol 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
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E.4 | Principal exclusion criteria |
1) Infection with any HCV genotype other than genotype 1 or an indeterminate or mixed genotype 2) History of having received any IFN, PEG-IFN, RBV, viramidine, levovirin, or investigational HCV polymerase or protease inhibitors at any previous time 3) History of having received any investigational drug less than or equal to 3 months prior to the first dose of study 4) Patients who are expected to need systemic antiviral therapy with established or perceived activity against HCV 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 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 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 16) History of immunologically mediated disease 17) History or other evidence of decompensated liver disease or a Child-Pugh score >6 18) History or other evidence of chronic pulmonary disease associated with functional limitation 19) History of severe cardiac disease. In addition, patients with documented or presumed coronary artery disease, stable or unstable cardiovascular disease or cerebrovascular disease should not be enrolled as an acute decrease in hemoglobin by up to 4 g/dL (as may be seen with ribavirin or RO4588161 therapy) may occur. 20) Patients with higher potential for QTC prolongation; patients with any clinical condition that increases the risk of QTC prolongation; personal or family history of congenital long QT syndrome or sudden death, which would make the patient, in the opinion of the investigator, unsuitable for the study 21) History of uncontrolled severe seizure disorder 22) Evidence of an active or suspected cancer, or a history of malignancy where the risk of recurrence is ≥ 20% within 2 years 23) History of any systemic anti-neoplastic or immunomodulatory treatment 24) Poorly controlled thyroid dysfunction 25) History or other evidence of a clinically relevant ophthalmologic disorder due to diabetes mellitus or hypertension or history or other evidence of severe retinopathy 26) History of major organ transplantation with an existing functional graft 27) History or other evidence of severe illness, malignancy or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study 28) Evidence of excessive alcohol, drug or substance abuse within 1 year of first dose
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary measure of efficacy is SVR defined as the 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 (SVR-24; a single last HCV RNA undetectable ≥ 20 weeks after last dose). Patients without HCV RNA measurements at the end of the 24-week treatment-free follow-up period will be considered non-responders. This definition of SVR will be “SVR according to actual treatment period”.
Additional analyses will be performed using the definition of SVR defined as the percentage of patients with undetectable HCV RNA as measured by Roche COBAS TaqMan HCV test at or after week 44 (≥ study day 309) for treatment Group C with total duration of 24 weeks or at or after week 68 (≥ study day 477) for treatment groups with total treatment duration of 48 weeks. This definition of SVR will be “SVR according to scheduled treatment period”.
All primary and secondary analyses of SVR will be performed using both definitions. Subgroup analysis and explorative analysis for SVR will be performed only for “SVR according to actual treatment period”.
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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 | Yes |
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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
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 | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.4.1 | Number of sites anticipated in Member State concerned | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 20 |
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 |
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E.8.7 | Trial has a data monitoring committee | Yes |
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
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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 |