Hepatitis C, Chronic
Conditions
Brief summary
To assess the pharmacokenetic characteristics of 600 mg BID BI 207127 / 120 mg QD faldaprevir /ribavirin in a small number of GT1b HCV infected patients with mild hepatic impairment (CPA) (Arm 1) versus 400 mg BID BI 207127 / 120 mg QD faldaprevir /ribavirin in a small number of GT1b HCV infected patients with moderate hepatic impairment (CPB) (Arm 2).
Interventions
DRUGRibavirin
24 Weeks
DRUGBI 207127 high dose
24 Weeks
DRUGFaldaprevir
24 Weeks
DRUGBI 207127 low dose
24 Weeks
Sponsors
Boehringer Ingelheim
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Treatment naïve and treatment experienced patients (prior relapse, interferon intolerant, and \[allowed in Cohort A only\] prior partial response). 2. Chronic HCV infection of genotype 1 (GT1), sub-GT1b virus only. 3. Liver cirrhosis defined as Metavir Grade=4 or Ishak Grade =5 on liver biopsy or liver stiffness of =13 kPa on fibroscan.
Exclusion criteria
1. HCV infection of mixed genotype (1/2, 1/3, and 1/4) or mixed sub-GT1a/1b or undefined diagnosed by genotypic testing at screening 2. Liver disease due to causes other than chronic HCV infection which may include but is not limited to hemochromatosis, Wilson's disease, or autoimmune liver diseases. 3. HIV infection 4. Patients who have been previously treated with an investigational or approved DAA
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| SVR12: Plasma HCV RNA Level Less Than 25 IU/mL at 12 Weeks After End of Treatment (EOT) | 12 weeks after End of Treatment | Sustained virologic response (SVR) at Week 12 post-treatment (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level \<25 IU/mL(international units per millilitre) at 12 weeks after EOT. SVR12 was analyzed in a descriptive manner using percentage. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SVR4: Plasma HCV RNA Level Less Than 25 IU/mL at 4 Weeks After End of Treatment (EOT) | 4 weeks after End of Treatment | Sustained virologic response (SVR) at Week 4 post-treatment (SVR4): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level \<25 IU/mL at 4 weeks after EOT. SVR4 was analyzed in a descriptive manner using percentage. |
Countries
Germany, Spain, United Kingdom, United States
Participant flow
Recruitment details
35 patients were enrolled and treated with Deleobuvir (DBV) / Faldaprevir (FDV) / Ribavirin (RBV): 18 patients with Child-Pugh A (mild hepatic impairment) and 17 patients with Child-Pugh B (moderate hepatic impairment).
Pre-assignment details
This was phase IIb open label study of BI 207127 (Deleobuvir) in combination with faldaprevir and ribavirin in patients with mild hepatic impairment (Child-Pugh A) and moderate hepatic impairment (Child-Pugh B) with genotype 1b chronic hepatitis C infection.
Participants by arm
| Arm | Count |
|---|---|
| Arm1: Child-Pugh A Arm 1 (genotype 1b) - 600mg DBV tablet taken orally twice daily (BID) plus 120mg FDV capsule taken orally once daily (QD) plus RBV tablet taken orally twice daily for 24 weeks. | 18 |
| Arm2: Child-Pugh B Arm 2 (genotype 1b) - 400mg DBV tablet taken orally twice daily (BID) plus 120mg FDV capsule taken orally once daily (QD) plus RBV tablet taken orally twice daily for 24 weeks. | 17 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 6 |
| Overall Study | Lack of Efficacy | 3 | 0 |
| Overall Study | Other reason not defined above | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Arm1: Child-Pugh A | Arm2: Child-Pugh B | Total |
|---|---|---|---|
| Age, Continuous | 57.8 Years STANDARD_DEVIATION 8.8 | 56.6 Years STANDARD_DEVIATION 9.7 | 57.2 Years STANDARD_DEVIATION 9.1 |
| Sex: Female, Male Female | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 17 / 18 | 17 / 17 |
| serious Total, serious adverse events | 1 / 18 | 9 / 17 |
Outcome results
Primary
SVR12: Plasma HCV RNA Level Less Than 25 IU/mL at 12 Weeks After End of Treatment (EOT)
Sustained virologic response (SVR) at Week 12 post-treatment (SVR12): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level \<25 IU/mL(international units per millilitre) at 12 weeks after EOT. SVR12 was analyzed in a descriptive manner using percentage.
Time frame: 12 weeks after End of Treatment
Population: (Treated Set) All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm1: Child-Pugh A | SVR12: Plasma HCV RNA Level Less Than 25 IU/mL at 12 Weeks After End of Treatment (EOT) | 61.1 Percentage of participants |
| Arm2: Child-Pugh B | SVR12: Plasma HCV RNA Level Less Than 25 IU/mL at 12 Weeks After End of Treatment (EOT) | 52.9 Percentage of participants |
Secondary
SVR4: Plasma HCV RNA Level Less Than 25 IU/mL at 4 Weeks After End of Treatment (EOT)
Sustained virologic response (SVR) at Week 4 post-treatment (SVR4): Plasma Hepatitis C virus Ribonucleic acid (HCV RNA) level \<25 IU/mL at 4 weeks after EOT. SVR4 was analyzed in a descriptive manner using percentage.
Time frame: 4 weeks after End of Treatment
Population: (Treated Set) All patients who were dispensed study medication and were documented to have taken at least one dose of investigational treatment, regardless of randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm1: Child-Pugh A | SVR4: Plasma HCV RNA Level Less Than 25 IU/mL at 4 Weeks After End of Treatment (EOT) | 72.2 Percentage of participants |
| Arm2: Child-Pugh B | SVR4: Plasma HCV RNA Level Less Than 25 IU/mL at 4 Weeks After End of Treatment (EOT) | 76.5 Percentage of participants |