Hepatitis C, Chronic
Conditions
Brief summary
The substances BI 201335 and BI 207127 are being developed for the treatment of chronic hepatitis C virus infection. BI 201335 and BI 207127 work by preventing the virus from replicating. The currently available medications pegylated interferon alfa and ribavirin for hepatitis C ca have considerable adverse events in patients and in many cases are not sufficiently effective. This is particularly the case in treatment of patients infected with genotype 1 of HCV. A combination therapy of these new substances without pegylated interferon alfa may be associated with fewer adverse events that currently available (pegylated interferon-alfa-based) medication and may also provide a treatment option to the large number of patients with contraindications or intolerance to pegylated interferon alfa. This clinical trial (1241.21) currently consists of 3 distinct studies: Part 1, Part 2 and Part 3. Part 1 (SOUND-C1) is a 2 armed study as described in experimental arms 1 and 2 below (actual enrollment: 56 patients; randomized and treated: 32) Part 2 (SOUND-C2) is a 5 armed study as described in experimental arms 3 to 7 below (actual enrollment: 465; randomized and treated: 362) Part 3 (SOUND-C3) includes 3 arms as described in experimental arms 8 to 10 below (83 patients randomized and treated)
Interventions
Sponsors
Boehringer Ingelheim
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis C virus (HCV) infection of genotype (GT) 1 * Parts 1-3:Treatment naive to Interferon -alfa (IFN), Pegylated interferon -alfa (PegIFN), ribavirin (RBV), and any direct acting antiviral agent for chronic hepatitis C * Part 4: Treatment experienced with confirmed prior virological failure to an approved dose of PegIFN/RBV (null-response) * HCV RNA \>=10,000 IU/mL at screening * Liver biopsy within two years or fibroscan within six months prior to baseline * Liver biopsy within two years or fibroscan within 6 months prior to screening * Age 18-75 years
Exclusion criteria
* Hepatitis C virus (HCV) infection of mixed genotype * Evidence of liver disease due to causes other than chronic HCV infection * Positive ELISA for human immunodeficiency virus (HIV) * Hepatitis B virus (HBV) infection * Decompensated liver disease or history of decompensated liver disease * Active or suspected malignancy within the last 5 years * Ongoing or historical photosensitivity or recurrent rash * History of alcohol or drug abuse (except cannabis) within the past 12 months * Body mass index (BMI)I \<18 or \> 35 kg/m2 * Usage of any investigational drugs within 30 days prior to enrolment, or 5 half-lives, whichever is longer; o the planned usage of an investigational drug during the course of the current study * Known hypersensitivity to any ingredient of the study drugs * A condition that is defined as one which in the opinion of the investigator may interfere with the patient's capability for participation in the trial or may influence the results of the trial * Alpha fetoprotein \>100ng/mL at screening; if \>20ng/mL and \<=100ng/mL, patients can be included if there is no evidence of liver cancer in an appropriate imaging study within 6 months prior to randomisation * Total bilirubin \> 2 mg/dL with ratio of direct/indirect \> 1 * AST or ALT \>5xULN * INR prolonged to \>1.7xULN * Requirement for chronic systemic corticosteroids * Received concomitant systemic antiviral, hematopoietic growth factor, or immunomodulatory treatment within 30 days prior to enrolment or 5 half-lives, whichever is longer * Received silymarin or glycyrrhizin or Sho-saiko-to within 30 days prior to enrolment * Contraindications pertaining to PegIFN or RBV
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part 1: Rapid Virological Response (RVR) | 4 weeks | Part 1: Rapid virological response (RVR), defined as Hepatitis C Virus Ribonucleic acid (HCV RNA) \<25IU/mL at Week 4 of treatment |
| Part 2: Sustained Virological Response (SVR) | From drug administration until 12 weeks after end of treatment, up to 52 weeks | Part 2: Sustained virological response (SVR), defined as HCV RNA \<25 IU/mL and undetectable at 12 weeks after end of treatment |
| Part 3 and 4: Sustained Virological Response (SVR) | From drug administration until 12 weeks after end of treatment, up to 36 weeks | Part 3 and 4: Sustained virological response (SVR) defined as HCV RNA \<25IU/mL and undetectable at 12 weeks after end of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | 4 weeks and 24 weeks after the end of treatment, up to 64 weeks | Part 2: Sustained virological response at 4 and 24 weeks after end of treatment |
| Part 1: Time to Virological Response | From drug administration until end of drug administration, up to 4 weeks | Part 1: Time to virological response, defined as the timepoint of the first measurement of plasma HCV RNA level \<25 IU/mL. The percentage of participants who achieved virological response within each time period are displayed for this outcome measure. |
| Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment | up to 28 weeks | Part 3 and 4: Sustained virological response (SVR) at 4 weeks after end of treatment |
| Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment | Week 4 and 12 | Part 3 and 4: Plasma Hepatitis C Virus Ribonucleic acid (HCV RNA) level \<25 IU/mL at week 4 and 12 of treatment |
| Part 2: Time to Virological Response | From drug administration until end of drug administration, up to 40 weeks | Part 2: Time to virological response, defined as the timepoint of the first measurement of plasma HCV RNA level \<25 IU/mL. The percentage of participants who achieved virological response within each time period are displayed for this outcome measure. |
| Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4 | 4 weeks | Part 1 and 2: Plasma Hepatitis C Virus Ribonucleic acid (HCV RNA) level not detectable at Week 4 |
Countries
Australia, Austria, France, Germany, New Zealand, Portugal, Romania, Spain, Switzerland, United States
Participant flow
Pre-assignment details
This trial was conducted in 4 parts, each consisting of randomised, open-label treatments.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w Part 1: 4 weeks of 400mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. From week 5 to week 24, patients received treatment with FDV 120mg QD in combination with standard of care (SOC) PegIFN/RBV (triple therapy period) | 15 |
| Part 1: 600mg DBV and 120mg FDV - 4w Part 1: 4 weeks of 600mg Deleobuvir (DBV, BI 207127) tablet three times per day (TID) and 120mg Faldaprevir (FDV, BI 201335) soft gelatin capsule once daily (QD) in combination with Ribavirin (RBV) tablet. From week 5 to week 24, patients received treatment with FDV 120mg QD in combination with SOC PegIFN/RBV (triple therapy period) | 17 |
| Part 2: 600mg DBV and 120mg FDV - 16w Part 2: 16 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks. | 81 |
| Part 2: 600mg DBV TID and 120mg FDV - 28w Part 2: 28 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks. | 80 |
| Part 2: 600mg DBV and 120mg FDV - 40w Part 2: 40 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks. | 77 |
| Part 2: 600mg DBV BID and 120mg FDV - 28w Part 2: 28 weeks of 600mg Deleobuvir tablet twice a day (BID) and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks. | 78 |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w Part 2: 28 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD, without RBV. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks. | 46 |
| Part 3: 600mg DBV and 120mg FDV - 16w Part 3: 16 weeks of 600mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks. | 32 |
| Part 3: 800mg DBV and 120mg FDV - 24w Part 3: 24 weeks of 800mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks. | 26 |
| Part 3: 600mg DBV and 120mg FDV - 24w Part 3: 24 weeks of 600mg Deleobuvir tablet TID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. Patients who discontinued their assigned treatment early due to lack of antiviral activity could receive additional treatment with PegIFN/RBV for up to 24 weeks. | 25 |
| Part 4: 600 mg DBV and 120mg FDV - 16w Part 4: 16 weeks of 600mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. | 1 |
| Part 4: 600 mg DBV and 120mg FDV - 24w Part 4: 24 weeks of 600mg Deleobuvir tablet BID and 120mg Faldaprevir soft gelatin capsule QD in combination with RBV tablet. | 2 |
| Total | 480 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 4 | 10 | 19 | 6 | 5 | 3 | 7 | 2 | 0 | 0 |
| Overall Study | Lack of antiviral response | 0 | 0 | 12 | 18 | 18 | 18 | 21 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lack of Efficacy | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 3 | 14 | 16 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Not treated | 2 | 0 | 0 | 0 | 2 | 1 | 3 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Other reason not defined above | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 3 | 3 | 6 | 0 | 1 | 0 | 0 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Part 2: 600mg DBV TID and 120mg FDV - 28w | Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: 600mg DBV and 120mg FDV - 16w | Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 3: 600mg DBV and 120mg FDV - 16w | Part 3: 800mg DBV and 120mg FDV - 24w | Part 3: 600mg DBV and 120mg FDV - 24w | Part 4: 600 mg DBV and 120mg FDV - 16w | Part 4: 600 mg DBV and 120mg FDV - 24w | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 47.3 Years STANDARD_DEVIATION 11.2 | 50.8 Years STANDARD_DEVIATION 10 | 50.8 Years STANDARD_DEVIATION 11.5 | 48.6 Years STANDARD_DEVIATION 11.3 | 48.9 Years STANDARD_DEVIATION 10.7 | 47.9 Years STANDARD_DEVIATION 11.1 | 45.3 Years STANDARD_DEVIATION 13 | 48.9 Years STANDARD_DEVIATION 11.8 | 47.2 Years STANDARD_DEVIATION 13.4 | 46.5 Years STANDARD_DEVIATION 12.5 | 59.0 Years | 52.5 Years STANDARD_DEVIATION 4.9 | 48.1 Years STANDARD_DEVIATION 11.4 |
| Sex: Female, Male Female | 39 Participants | 7 Participants | 7 Participants | 36 Participants | 41 Participants | 37 Participants | 22 Participants | 20 Participants | 11 Participants | 11 Participants | 1 Participants | 2 Participants | 234 Participants |
| Sex: Female, Male Male | 41 Participants | 8 Participants | 10 Participants | 45 Participants | 36 Participants | 41 Participants | 24 Participants | 12 Participants | 15 Participants | 14 Participants | 0 Participants | 0 Participants | 246 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 17 | 76 / 81 | 71 / 80 | 74 / 77 | 73 / 78 | 43 / 46 | 30 / 32 | 26 / 26 | 25 / 25 | 1 / 1 | 2 / 2 |
| serious Total, serious adverse events | 0 / 15 | 0 / 17 | 3 / 81 | 8 / 80 | 6 / 77 | 8 / 78 | 3 / 46 | 1 / 32 | 3 / 26 | 2 / 25 | 0 / 1 | 0 / 2 |
Outcome results
Primary
Part 1: Rapid Virological Response (RVR)
Part 1: Rapid virological response (RVR), defined as Hepatitis C Virus Ribonucleic acid (HCV RNA) \<25IU/mL at Week 4 of treatment
Time frame: 4 weeks
Population: FAS which included all randomised patients who were dispensed study medication and were documented to have taken at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Rapid Virological Response (RVR) | 73.3 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Rapid Virological Response (RVR) | 100.0 Percentage of participants |
Primary
Part 2: Sustained Virological Response (SVR)
Part 2: Sustained virological response (SVR), defined as HCV RNA \<25 IU/mL and undetectable at 12 weeks after end of treatment
Time frame: From drug administration until 12 weeks after end of treatment, up to 52 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Sustained Virological Response (SVR) | 59.3 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Sustained Virological Response (SVR) | 58.8 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Sustained Virological Response (SVR) | 51.9 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Sustained Virological Response (SVR) | 69.2 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Sustained Virological Response (SVR) | 39.1 Percentage of participants |
Primary
Part 3 and 4: Sustained Virological Response (SVR)
Part 3 and 4: Sustained virological response (SVR) defined as HCV RNA \<25IU/mL and undetectable at 12 weeks after end of treatment
Time frame: From drug administration until 12 weeks after end of treatment, up to 36 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 3 and 4: Sustained Virological Response (SVR) | 65.6 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 3 and 4: Sustained Virological Response (SVR) | 19.2 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 3 and 4: Sustained Virological Response (SVR) | 12.0 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 3 and 4: Sustained Virological Response (SVR) | NA Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 3 and 4: Sustained Virological Response (SVR) | NA Percentage of participants |
Secondary
Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4
Part 1 and 2: Plasma Hepatitis C Virus Ribonucleic acid (HCV RNA) level not detectable at Week 4
Time frame: 4 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4 | 20.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4 | 70.6 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4 | 65.4 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4 | 60.0 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4 | 63.6 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4 | 56.4 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 1 and 2: Plasma HCV RNA Level Not Detectable at Week 4 | 50.0 Percentage of participants |
Secondary
Part 1: Time to Virological Response
Part 1: Time to virological response, defined as the timepoint of the first measurement of plasma HCV RNA level \<25 IU/mL. The percentage of participants who achieved virological response within each time period are displayed for this outcome measure.
Time frame: From drug administration until end of drug administration, up to 4 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 8 weeks | 53.3 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 4 weeks | 20.0 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 32 weeks | 6.7 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 12 weeks | 0.0 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 40 weeks | 0.0 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 2 weeks | 6.7 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | > 40 weeks | 0.0 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 16 weeks | 6.7 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | Never | 6.7 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 28 weeks | 0.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | Never | 0.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 2 weeks | 11.8 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 4 weeks | 47.1 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 8 weeks | 41.2 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 12 weeks | 0.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 16 weeks | 0.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 28 weeks | 0.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 32 weeks | 0.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | <= 40 weeks | 0.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 1: Time to Virological Response | > 40 weeks | 0.0 Percentage of participants |
Secondary
Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment
Part 2: Sustained virological response at 4 and 24 weeks after end of treatment
Time frame: 4 weeks and 24 weeks after the end of treatment, up to 64 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR4 | 60.5 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR24 | 58.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR4 | 62.5 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR24 | 58.8 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR4 | 54.5 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR24 | 49.4 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR24 | 69.2 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR4 | 69.2 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR4 | 43.5 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Sustained Virological Response at 4 and 24 Weeks After End of Treatment | SVR24 | 39.1 Percentage of participants |
Secondary
Part 2: Time to Virological Response
Part 2: Time to virological response, defined as the timepoint of the first measurement of plasma HCV RNA level \<25 IU/mL. The percentage of participants who achieved virological response within each time period are displayed for this outcome measure.
Time frame: From drug administration until end of drug administration, up to 40 weeks
Population: FAS
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 0 (N=81, 80, 77, 78, 46) | 0.0 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 8(N=75, 72, 72, 75, 44) | 3.8 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 57 (N=9, 8, 9, 11, 9) | 88.1 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 141 (N=9, 7, 8, 11, 8) | 88.1 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 29 (N=29, 32, 27, 32, 21) | 61.5 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 85 (N=9, 7, 8, 11, 9) | 88.1 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 169 (N=9, 7, 8, 11, 8) | 88.1 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 15 (N=62, 61, 63, 60, 33) | 19.4 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 113 (N=9, 7, 8, 11, 8) | 88.1 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 43 (N=16, 12, 13, 18, 12) | 78.8 Percentage of participants |
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 197 (N=9, 7, 8, 11, 8) | 88.1 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 43 (N=16, 12, 13, 18, 12) | 83.3 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 85 (N=9, 7, 8, 11, 9) | 90.3 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 57 (N=9, 8, 9, 11, 9) | 88.9 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 0 (N=81, 80, 77, 78, 46) | 0.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 169 (N=9, 7, 8, 11, 8) | 90.3 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 15 (N=62, 61, 63, 60, 33) | 20.7 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 8(N=75, 72, 72, 75, 44) | 7.7 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 141 (N=9, 7, 8, 11, 8) | 90.3 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 29 (N=29, 32, 27, 32, 21) | 55.5 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 197 (N=9, 7, 8, 11, 8) | 90.3 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 2: Time to Virological Response | Day 113 (N=9, 7, 8, 11, 8) | 90.3 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 57 (N=9, 8, 9, 11, 9) | 85.1 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 0 (N=81, 80, 77, 78, 46) | 0.0 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 8(N=75, 72, 72, 75, 44) | 1.4 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 15 (N=62, 61, 63, 60, 33) | 9.9 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 29 (N=29, 32, 27, 32, 21) | 59.4 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 43 (N=16, 12, 13, 18, 12) | 80.5 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 85 (N=9, 7, 8, 11, 9) | 86.8 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 113 (N=9, 7, 8, 11, 8) | 86.8 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 141 (N=9, 7, 8, 11, 8) | 86.8 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 169 (N=9, 7, 8, 11, 8) | 86.8 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 2: Time to Virological Response | Day 197 (N=9, 7, 8, 11, 8) | 86.8 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 29 (N=29, 32, 27, 32, 21) | 57.7 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 0 (N=81, 80, 77, 78, 46) | 0.0 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 8(N=75, 72, 72, 75, 44) | 2.6 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 197 (N=9, 7, 8, 11, 8) | 85.5 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 169 (N=9, 7, 8, 11, 8) | 85.5 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 15 (N=62, 61, 63, 60, 33) | 22.1 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 57 (N=9, 8, 9, 11, 9) | 85.5 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 113 (N=9, 7, 8, 11, 8) | 85.5 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 141 (N=9, 7, 8, 11, 8) | 85.5 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 43 (N=16, 12, 13, 18, 12) | 76.2 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 2: Time to Virological Response | Day 85 (N=9, 7, 8, 11, 9) | 85.5 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 0 (N=81, 80, 77, 78, 46) | 0.0 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 85 (N=9, 7, 8, 11, 9) | 78.0 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 29 (N=29, 32, 27, 32, 21) | 48.6 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 113 (N=9, 7, 8, 11, 8) | 80.4 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 15 (N=62, 61, 63, 60, 33) | 19.3 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 197 (N=9, 7, 8, 11, 8) | 80.4 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 141 (N=9, 7, 8, 11, 8) | 80.4 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 8(N=75, 72, 72, 75, 44) | 2.2 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 169 (N=9, 7, 8, 11, 8) | 80.4 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 57 (N=9, 8, 9, 11, 9) | 78.0 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 2: Time to Virological Response | Day 43 (N=16, 12, 13, 18, 12) | 70.7 Percentage of participants |
Secondary
Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment
Part 3 and 4: Plasma Hepatitis C Virus Ribonucleic acid (HCV RNA) level \<25 IU/mL at week 4 and 12 of treatment
Time frame: Week 4 and 12
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment | 75.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment | 26.9 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment | 32.0 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment | NA Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 3 and 4: Plasma HCV RNA Level <25 IU/mL at Week 4 and 12 of Treatment | NA Percentage of participants |
Secondary
Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment
Part 3 and 4: Sustained virological response (SVR) at 4 weeks after end of treatment
Time frame: up to 28 weeks
Population: FAS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1: 400mg DBV and 120mg FDV - 4w | Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment | 75.0 Percentage of participants |
| Part 1: 600mg DBV and 120mg FDV - 4w | Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment | 19.2 Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV - 40w | Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment | 12.0 Percentage of participants |
| Part 2: 600mg DBV BID and 120mg FDV - 28w | Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment | NA Percentage of participants |
| Part 2: 600mg DBV and 120mg FDV, no RBV - 28w | Part 3 and 4: Sustained Virological Response (SVR) at 4 Weeks After End of Treatment | NA Percentage of participants |