A Randomized, Partially-blind Study to Evaluate the Safety, Tolerability and Effect on Virological Response of Treatment with the HCV Protease Inhibitor RO5190591 in combination with Pegasys and Copegus for 12 weeks, versus treatment with Pegasys and Copegus alone, in Treatment-Naïve Patients with Chronic Hepatitis C Genotype 1 Virus Infection

• Register: EUCTR
• Last refreshed on: 16 October 2012
• Main ID: EUCTR2009-009608-38-DE
• Date of registration: 15/06/2009
• Prospective Registration: Yes
• Primary sponsor: F.Hoffmann-La Roche
• Public title: A Randomized, Partially-blind Study to Evaluate the Safety, Tolerability and Effect on Virological Response of Treatment with the HCV Protease Inhibitor RO5190591 in combination with Pegasys and Copegus for 12 weeks, versus treatment with Pegasys and Copegus alone, in Treatment-Naïve Patients with Chronic Hepatitis C Genotype 1 Virus Infection
• Scientific title: A Randomized, Partially-blind Study to Evaluate the Safety, Tolerability and Effect on Virological Response of Treatment with the HCV Protease Inhibitor RO5190591 in combination with Pegasys and Copegus for 12 weeks, versus treatment with Pegasys and Copegus alone, in Treatment-Naïve Patients with Chronic Hepatitis C Genotype 1 Virus Infection
• Date of first enrolment: 14/06/2010
• Target sample size: 300
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-009608-38
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Partially Blind If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no

Countries of recruitment

Austria, France, Germany, Italy

Key inclusion & exclusion criteria

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-naïve (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
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) yes
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Infection with any HCV genotype other than genotype 1 or an indeterminate or mixed genotype. Genotype 1 pts w indeterminate or mixed subtypes will be allowed
2. History of having received any IMP = 3m prior to the 1st dose of study drug or the expectation that such drugs will be used during the study. Pts enrolled in this study cannot be enrolled in another study for either research, diagnostic or treatment purposes Pts 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 excl
4. + 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
6. Females who are pregnant or breast feeding
7. Male partners of females who are pregnant
8. BMI < 18 or = 36
9. Absolute neutrophil count (ANC) < 1.5 x 103 / µL (< 1.5 x 109 /L)
10. Platelet count < 90 x 103 / µL (< 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 pt w a baseline increased risk for anemia or for whom anemia would be medically problematic
12. Serum creatinine level > 1.5* 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 6m
14. Hist of severe psychiatric disease, incl 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 add, pts w a concurrent psychiatric condition or history of a psychiatric condition that, in the opinion of the Inv and/or Psychiatrist, would compromise participation in this study
15. Hist of immunologically mediated disease
17. Poorly controlled hypertension, with a hist of poor adherence to antihypertensive therapy or screening or baseline blood pressure of systolic = 160 mmHg and/or diastolic =100 mmHg
18. Type I or II diabetes with HbA1C > 8.5% at the Screening Visit
19. Hist or other evidence of chronic pulmonary disease associated with functional
limitation
20. Hist of severe cardiac disease. In add, pts w doc or presumed coronary artery disease, stable or unstable cardiovascular disease or cerebrovascular disease should not be enrolled
21. Pts w higher potential for QTC prolongation; defined by QTC = 450 ms, or notable resting bradycardia < 50 beats/min, or notable resting tachycardia > 100 beats/min or personal or family history of congenital long QT syndrome or sudden death
22. Hist of uncontrolled severe seizure disorder
23. Evidence of an active or suspected cancer, or a history of malignancy where the risk of recurrence is = 20% within 2y.
24. Hist of any systemic anti-neoplastic or immunomodulatory treatment (incl supraphysiologic doses of steroids and radiation) = 6m prior to the 1st dose of study drug or the expectation that such treatment will be needed at any time during the study
25. Poorly controlled thyroid dysfunction
26. Hist or other evidence of a clinically relevant ophthalmologic disorder due to
diabetes mellitus or hypertension or history /other evidence of severe retinopathy
27. Hist of major organ transplantation with an existing functional graft
28. Hist or other evidence

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

Health Condition(s) or Problem(s) studied

Chronic Hepatitis C Genotype 1 Virus Infection (Treatment-Naive Patients)
MedDRA version: 9.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C

Intervention(s)

Product Name: HCV-Protease
Product Code: RO5190591/F02 (ITMN-191)
Pharmaceutical Form: Capsule, soft
Current Sponsor code: RO519-0591/F02 (ITMN-191)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 100-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Product Name: HCV-Protease
Product Code: RO5190591/F10(ITMN-191)
Pharmaceutical Form: Capsule, soft
Current Sponsor code: RO519-0591/F10 (ITMN-191)
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-
Pharmaceutical form of the placebo: Capsule, soft
Route of administration of the placebo: Oral use

Trade Name: Pegasys
Pharmaceutical Form: Solution for injection
INN or Proposed INN: pegylated interfron alfa-2a
CAS Number: 198153-51-4
Current Sponsor code: Ro 25-8310
Other descriptive name: pegylated interfron alfa-2a
Concentration unit: µg microgram(s)
Concentration type: equal
Concentration number: 180-

Trade Name: Copegus
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Ribavirin
CAS Number: 36791-04-5
Current Sponsor code: RO20-9963
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: To evaluate the safety, tolerability, and effect on virologicalresponse of a 12 weeks duration of RO5190591 incombination with Pegasys and Copegus compared to thecombination of Pegasys and Copegus alone in treatment-naïvepatients with chronic hepatitis C genotype 1 virus infection

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”.

Secondary Objective: 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

Secondary ID(s)

NV21075