| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Chronic Hepatitis C (CHC) Genotype 1 |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10008912 |
| E.1.2 | Term | Chronic 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 evaluate the safety, tolerability, and effect on virological
response of a 12 and 24-week duration of RO5190591 in combination with Pegasys and Copegus compared to the
combination of Pegasys and Copegus alone in treatment-na�ve
patients with chronic hepatitis C genotype 1 virus infection. |
|
| E.2.2 | Secondary objectives of the trial |
-To evaluate the pharmacokinetics of RO5190591 in combination
with Pegasys and Copegus;
-To evaluate the viral resistance profile of RO5190591 in
combination with Pegasys and Copegus. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Age 18 years and older;
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 infection by molecular assay;
5. Serum HCV RNA quantifiable at ≥ 50,000 IU/mL as demonstrated by the Roche COBAS TaqMan HCV Test;
6. HCV treatment-na�ve (i.e. have never received treatment for CHC, including but not limited to IFN-based therapy, ribavirin, or other anti-viral agents with established or
perceived activity against the HCV virus);
7. Liver biopsy within the past 24 months showing clear absence of advanced fibrosis or cirrhosis (as indicated in Appendix 1). Liver biopsy should be scored using one of
the scoring methods in Appendix 1;
8. Normal cardiac troponin I (cTnI) value at the screening visit (< 0.100 ng/mL);
9. Serum total bilirubin value at the screening visit within the reference range;
10. 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 a 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;
11. 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
(for example, genotype 1a/b);
2. History of having received any investigational drug &#8804; 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; 3. 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; 4. Positive test at screening for anti-HAV IgM Ab, HBsAg, anti-HBc IgM Ab, or anti-HIV Ab;
5. History or other evidence of a medical condition associated with chronic liver disease other than HCV (e.g., hemochromatosis, autoimmune hepatitis, Wilsons disease,
&#945;1-antitrypsin deficiency, metabolic liver disease, alcoholic liver disease, and/or toxin exposure);
6. Females who are pregnant or breast feeding; 7. Male partners of females who are pregnant; 8. Body mass index (BMI) < 18 or &#8805; 36; 9. Absolute neutrophil count (ANC) < 1.5 x 103 / &#956;L (< 1.5 x 109 /L); 10. Platelet count < 90 x 103 / &#956;L (< 90 x 109 /L);
11. Hemoglobin (Hgb) concentration < 11 g/dL (< 110 g/L) in females or < 12 g/dL (< 120 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; 12. Serum creatinine level > 1.5 times the upper limit of normal at screening; 13. 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; 14. History of severe psychiatric disease, including psychosis and/or severe depression,
characterized by a suicide attempt, hospitalization for psychiatric disease, or a period
of disability as a result of psychiatric disease. In addition, patients with a concurrent
psychiatric condition or history of a psychiatric condition that, in the opinion of the Investigator and/or Psychiatrist, would compromise participation in this study;
15. History of immunologically mediated disease (e.g., vasculitis, cryoglobulinemia, 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 anti-inflammatory medications for management, etc); 16. History or other evidence of decompensated liver disease. Coagulopathy,
hyperbilirubinemia, hepatic encephalopathy, hypoalbuminemia, ascites, and bleeding from esophageal varices are conditions consistent with decompensated liver disease; 17. Poorly controlled hypertension, with a history of poor adherence to antihypertensive therapy or screening or baseline blood pressure of systolic &#8805; 160 mmHg and/or
diastolic &#8805;100 mmHg; 18. Type I or II diabetes with HbA1C > 8.5% at the Screening Visit; 19. History or other evidence of chronic pulmonary disease associated with functional limitation; Et al... |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
SVR-24: 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 &#8805; 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. |
|
| 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 | No |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
| Resistenza virale, Analisi di biomarcatori |
|
| 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 | No |
| E.8.1.5 | Parallel group | No |
| 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
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| 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 | 8 |
| 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 | 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
|
| Lo studio termina con la LPLV. La LPLV corrisponde alla data della LPLV per completare lo studio oppure alla data in cui sono stati ricevuti gli ultimi dati dallultimo paziente (richiesti per lanalisi statistica),quella che si verifica piu` tardi. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 1 |
| E.8.9.1 | In the Member State concerned days | |
Print
