Hepatitis C
Conditions
Brief summary
The objective of this trial is to evaluate the efficacy and safety of two different treatment regimens with BI 201335, both in combination with PegIFN/RBV) as compared to standard of care (SOC) with PegIFN/RBV alone.
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Chronic hepatitis C infection, diagnosed by positive anti-HCV antibodies and detected HCV RNA at screening in addition to: 1. positive anti-HCV antibodies or detected HCV RNA at least 6 months prior to screening; or, 2. liver biopsy consistent with chronic HCV infection. 2. HCV genotype 1 infection confirmed by genotypic testing at screening. 3. Therapy-naïve to interferon, pegylated interferon, ribavirin or any antiviral / immunomodulatory drug for acute or chronic HCV infection. 4. HCV RNA = 1,000 IU/mL at screening 5. Documentation of a liver biopsy within 3 years or fibroscan within 6 months prior to randomization. Note: If cirrhosis has been previously demonstrated on a biopsy, then biopsies obtained more than 3 years before randomization need not be repeated. Biopsies may be waived for patients who would be placed at risk from the procedure. Inability to do a liver biopsy in patients at risk for the procedure should not exclude such patients from a trial. 6. Age 18 to 70 years 7. Female patients: 1. with documented hysterectomy, 2. who have had both ovaries removed, 3. with documented tubal ligation, 4. who are post-menopausal with last menstrual period at least 12 months prior to screening, or 5. of childbearing potential with a negative serum pregnancy test at screening and Day 1, that, if sexually active, agree to use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin in addition to the consistent and correct use of a condom. Patients must agree not to breast-feed at any time from the date of screening until 7 months after the last dose of ribavirin. Medically accepted methods of contraception for females in this trial are ethinyl estradiol containing contraceptives, diaphragm with spermicide substance and intra-uterine device. Male patients: 1. who are documented to be sterile, or 2. who are without pregnant female partner(s) and consistently and correctly use a condom while their female partner(s) (if of child-bearing potential) use one of the appropriate medically accepted methods of birth control from the date of screening until 7 months after the last dose of ribavirin. It is in the responsibility of the male patient to ensure that his partner(s) is not pregnant prior to screening into the study or becomes pregnant during the treatment and the observation phase. Female partners of childbearing potential should perform monthly pregnancy tests from the date of screening until 7 months after the last dose of ribavirin (tests will be provided by the sponsor). 8. Signed informed consent form prior to trial participation
Exclusion criteria
1. HCV infection of mixed genotype (1/2, 1/3, and 1/4) diagnosed by genotypic testing at screening 2. Evidence of acute or chronic liver disease due to causes other than chronic HCV infection. Incidental steatosis diagnosed by biopsy is not an exclusion criterion. 3. HIV co-infection 4. Hepatitis B virus (HBV) infection based on presence of HBs-Ag 5. Active malignancy, or history of malignancy within the last 5 years prior to screening (with an exception of appropriately treated basal cell carcinoma of the skin or in situ carcinoma of the uterine cervix) 6. Active or, history of alcohol or illicit drug abuse other than cannabis within the past 12 months 7. A condition that is defined as one which in the opinion of investigator may put the patient at risk because of participation in this study, may influence the results of this study, or limit the patients ability to participate in this study 8. Usage of any investigational drugs within 30 days prior to screening, or planned usage of an investigational drug during the course of this study. 9. Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to randomization. Patients being treated with oral antivirals such as acyclovir, famciclovir or valacyclovir for recurrent herpes simplex infection; or with oseltamivir or zanamivir for influenza A infection, may be screened. 10. Received silymarin (milk thistle), glycyrrhizin, or Sho-saiko-to (SST) within 28 days prior to randomization and throughout the treatment phase of this trial. 11. Known hypersensitivity to any ingredient of the study drugs. 12. Alpha fetoprotein value \> 100 ng/mL at screening; if \> 20 ng/mL and = 100 ng/mL, patients may be included if there is no evidence of liver cancer in an appropriate imaging study (e.g., ultrasound, CT scan, or MRI) within last 6 months prior to randomization (Visit 2). Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Sustained Virological Response 12 Weeks Post-treatment (SVR12) | 12 weeks post treatment, up to 60 weeks | Sustained Virological Response 12 weeks post-treatment (SVR12), defined as plasma Hepatitis C virus (HCV) Ribonucleic acid (RNA) level \< 25 IU/mL (undetected) 12 weeks after the originally planned treatment duration. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Early Treatment Success (ETS) | week 4 and week 8 | Early treatment success (ETS), defined as a plasma HCV RNA level \<25 IU/mL (detected or undetected) at week 4 and HCV RNA \<25 IU/mL (undetected) at week 8. |
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | 12 weeks post treatment, up to 60 weeks | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline |
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | 12 weeks post treatment, up to 60 weeks | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline |
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | 12 weeks post treatment, up to 60 weeks | This will be presented as the number of patients. BL = Baseline |
| Sustained Virological Response 24 Weeks Post-treatment (SVR24) | 24 weeks post treatment, up to 72 weeks | Sustained Virological Response 24 weeks post-treatment (SVR24), defined as plasma HCV RNA level \< 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration. |
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | 12 weeks post treatment, up to 60 weeks | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline |
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | 12 weeks post treatment, up to 60 weeks | This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline |
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | 12 weeks post treatment, up to 60 weeks | This will be presented as the number of patients. BL = Baseline |
| Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | 12 weeks post treatment, up to 60 weeks | This will be presented as the number of patients. BL = Baseline |
| Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | 12 weeks post treatment, up to 60 weeks | This will be presented as the number of patients. BL = Baseline |
Countries
Austria, Belgium, France, Germany, Japan, Portugal, Romania, Russia, Spain, Switzerland, United Kingdom
Participant flow
Pre-assignment details
All subjects were screened for eligibility to participate in the trial. Subjects attended specialist sites which would then ensure that they (the subject) met all strictly implemented inclusion/exclusion criteria. Subjects were not to be randomised to trial treatment if any one of the specific entry criteria were violated.
Participants by arm
| Arm | Count |
|---|---|
| Faldaprevir 120mg and PegIFN/RBV Faldaprevir 120 mg once daily (oral) plus PegIFN/RBV (subcutaneous injection/oral) for 12 or 24 weeks, followed by PegIFN/RBV alone up to Week 24 or 48. | 259 |
| Faldaprevir 240mg and PegIFN/RBV Faldaprevir 240 mg once daily (oral) plus PegIFN/RBV (subcutaneous injection/oral) for 12 weeks, followed by PegIFN/RBV up to Week 24 or 48. | 261 |
| Placebo and PegIFN/RBV Placebo (oral) once daily plus PegIFN/RBV (subcutaneous injection/oral) for 24 weeks, followed by PegIFN/RBV alone up to Week 48. | 132 |
| Total | 652 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 12 | 22 | 5 |
| Overall Study | Lack of Efficacy | 9 | 9 | 13 |
| Overall Study | Lost to Follow-up | 0 | 2 | 1 |
| Overall Study | other than stated above | 0 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 2 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 4 | 2 |
Baseline characteristics
| Characteristic | Faldaprevir 120mg and PegIFN/RBV | Faldaprevir 240mg and PegIFN/RBV | Placebo and PegIFN/RBV | Total |
|---|---|---|---|---|
| Age, Continuous | 47.9 years STANDARD_DEVIATION 11.44 | 48.3 years STANDARD_DEVIATION 11.89 | 46.6 years STANDARD_DEVIATION 12.53 | 47.8 years STANDARD_DEVIATION 11.85 |
| Sex: Female, Male Female | 138 Participants | 115 Participants | 57 Participants | 310 Participants |
| Sex: Female, Male Male | 121 Participants | 146 Participants | 75 Participants | 342 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 246 / 259 | 250 / 261 | 120 / 132 |
| serious Total, serious adverse events | 17 / 259 | 17 / 261 | 8 / 132 |
Outcome results
Primary
Sustained Virological Response 12 Weeks Post-treatment (SVR12)
Sustained Virological Response 12 weeks post-treatment (SVR12), defined as plasma Hepatitis C virus (HCV) Ribonucleic acid (RNA) level \< 25 IU/mL (undetected) 12 weeks after the originally planned treatment duration.
Time frame: 12 weeks post treatment, up to 60 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Sustained Virological Response 12 Weeks Post-treatment (SVR12) | 79.5 percentage of participants |
| Faldaprevir 240mg and PegIFN/RBV | Sustained Virological Response 12 Weeks Post-treatment (SVR12) | 80.5 percentage of participants |
| Placebo and PegIFN/RBV | Sustained Virological Response 12 Weeks Post-treatment (SVR12) | 52.3 percentage of participants |
p-value: <0.000195% CI: [17.9, 37]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [19, 38.2]Cochran-Mantel-Haenszel
95% CI: [-7.9, 5.8]
Secondary
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO
This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline
Time frame: 12 weeks post treatment, up to 60 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No, BL elevated to EoT normal | 16 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No | 53 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No, No ALT data available at EoT | 0 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No, BL normal to EoT normal | 15 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No, BL elevated to EoT normal | 22 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No, BL normal to EoT normal | 10 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No | 51 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No, No ALT data available at EoT | 0 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No, No ALT data available at EoT | 1 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No | 63 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No, BL normal to EoT normal | 15 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12= NO | SVR12 = No, BL elevated to EoT normal | 20 participants |
Secondary
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES
This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline
Time frame: 12 weeks post treatment, up to 60 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes | 206 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL normal to EoT normal | 66 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL elevated to EoT normal | 97 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, No ALT data available at EoT | 0 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, No ALT data available at EoT | 0 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes | 210 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL elevated to EoT normal | 115 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL normal to EoT normal | 68 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, No ALT data available at EoT | 0 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL normal to EoT normal | 27 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL elevated to EoT normal | 31 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes | 69 participants |
Secondary
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO
This will be presented as the number of patients. BL = Baseline
Time frame: 12 weeks post treatment, up to 60 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL elevated to SVR12 normal | 6 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No | 53 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, No ALT data available post-treatment | 8 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL normal to SVR12 normal | 9 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL elevated to SVR12 normal | 6 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL normal to SVR12 normal | 5 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No | 51 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, No ALT data available post-treatment | 14 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL normal to SVR12 normal | 5 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No | 63 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, No ALT data available post-treatment | 45 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL elevated to SVR12 normal | 1 participants |
Secondary
Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES
This will be presented as the number of patients. BL = Baseline
Time frame: 12 weeks post treatment, up to 60 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes | 206 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL normal to SVR12 normal | 72 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL elevated to SVR12 normal | 125 participants |
| Faldaprevir 120mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, No ALT data available post-treatment | 4 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL normal to SVR12 normal | 73 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, No ALT data available post-treatment | 5 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL elevated to SVR12 normal | 126 participants |
| Faldaprevir 240mg and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes | 210 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL elevated to SVR12 normal | 39 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL normal to SVR12 normal | 27 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes | 69 participants |
| Placebo and PegIFN/RBV | Alanine Aminotransferase (ALT) Normalisation: ALT in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, No ALT data available post-treatment | 1 participants |
Secondary
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO
This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline
Time frame: 12 weeks post treatment, up to 60 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No, BL elevated to EoT normal | 14 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No, BL normal to EoT normal | 17 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No | 53 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No, No AST data available at EoT | 0 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No, BL normal to EoT normal | 16 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No | 51 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No, No AST data available at EoT | 0 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No, BL elevated to EoT normal | 16 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No | 63 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No, No AST data available at EoT | 1 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No, BL elevated to EoT normal | 13 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=NO | SVR12 = No, BL normal to EoT normal | 21 participants |
Secondary
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES
This will be presented as the number of patients. SVR12 means Sustained virological response 12 weeks post-treatment. BL = Baseline
Time frame: 12 weeks post treatment, up to 60 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes | 206 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL normal to EoT normal | 95 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL elevated to EoT normal | 74 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, No AST data available at EoT | 0 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, No AST data available at EoT | 0 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes | 210 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL elevated to EoT normal | 76 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL normal to EoT normal | 99 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, No AST data available at EoT | 0 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL normal to EoT normal | 34 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes, BL elevated to EoT normal | 25 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at End of Treatment (EoT) When SVR12=YES | SVR12 = Yes | 69 participants |
Secondary
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO
This will be presented as the number of patients. BL = Baseline
Time frame: 12 weeks post treatment, up to 60 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL elevated to SVR12 normal | 10 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL normal to SVR12 normal | 10 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No | 53 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, No AST data available post-treatment | 8 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL normal to SVR12 normal | 10 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No | 51 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL elevated to SVR12 normal | 5 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, No AST data available post-treatment | 14 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL elevated to SVR12 normal | 1 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, BL normal to SVR12 normal | 5 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No | 63 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=NO | SVR12 = No, No AST data available post-treatment | 45 participants |
Secondary
Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES
This will be presented as the number of patients. BL = Baseline
Time frame: 12 weeks post treatment, up to 60 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes | 206 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL normal to SVR12 normal | 102 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL elevated to SVR12 normal | 90 participants |
| Faldaprevir 120mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, No AST data available post-treatment | 5 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, No AST data available post-treatment | 5 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes | 210 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL elevated to SVR12 normal | 88 participants |
| Faldaprevir 240mg and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL normal to SVR12 normal | 109 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, No AST data available post-treatment | 1 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL normal to SVR12 normal | 39 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes, BL elevated to SVR12 normal | 27 participants |
| Placebo and PegIFN/RBV | Aspartate Aminotransferase (AST) Normalisation: AST in Normal Range at Sustained Virological Response 12 Weeks Post-treatment (SVR12) Visit, When SVR12=YES | SVR12 = Yes | 69 participants |
Secondary
Early Treatment Success (ETS)
Early treatment success (ETS), defined as a plasma HCV RNA level \<25 IU/mL (detected or undetected) at week 4 and HCV RNA \<25 IU/mL (undetected) at week 8.
Time frame: week 4 and week 8
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Early Treatment Success (ETS) | 87.3 percentage of participants |
| Faldaprevir 240mg and PegIFN/RBV | Early Treatment Success (ETS) | 89.3 percentage of participants |
| Placebo and PegIFN/RBV | Early Treatment Success (ETS) | 22.0 percentage of participants |
Secondary
Sustained Virological Response 24 Weeks Post-treatment (SVR24)
Sustained Virological Response 24 weeks post-treatment (SVR24), defined as plasma HCV RNA level \< 25 IU/mL (undetected) 24 weeks after the originally planned treatment duration.
Time frame: 24 weeks post treatment, up to 72 weeks
Population: Full analysis set (FAS) included all randomized patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Faldaprevir 120mg and PegIFN/RBV | Sustained Virological Response 24 Weeks Post-treatment (SVR24) | 79.2 percentage of participants |
| Faldaprevir 240mg and PegIFN/RBV | Sustained Virological Response 24 Weeks Post-treatment (SVR24) | 79.7 percentage of participants |
| Placebo and PegIFN/RBV | Sustained Virological Response 24 Weeks Post-treatment (SVR24) | 52.3 percentage of participants |
p-value: <0.000195% CI: [17.5, 36.7]Cochran-Mantel-Haenszel
p-value: <0.000195% CI: [18.2, 37.4]Cochran-Mantel-Haenszel
95% CI: [-7.6, 6.3]