Chronic Hepatitis C Virus (HCV)
Conditions
Keywords
HCV Infection, Compensated Cirrhosis
Brief summary
This is a Phase 3, open-label, multicenter study evaluating the efficacy and safety of ABT-450/r/ ABT-267 and ABT-333 coadministered with RBV for 12 weeks in HCV genotype 1b, treatment naïve and Interferon (IFN) (alpha, beta or pegIFN) plus RBV treatment-experienced Asian adults with compensated cirrhosis.
Interventions
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Chinese, South Korean, and Taiwanese descent with full Chinese, South Korean, and Taiwanese parentage. 2. Chronic HCV-infection prior to study enrollment. 3. Screening laboratory result indicating HCV genotype 1b-infection. 4. Compensated cirrhosis defined as a Child-Pugh Score of less than or equal to 6 at Screening. 5. Per local standard practice, documentation of cirrhosis by one of the following methods: * Diagnosis on previous liver biopsy or liver biopsy conducted during screening e.g., Metavir Score of \> 3 (including 3/4 or 3 - 4), Ishak score of \> 4 or, * FibroScan score ≥ 14.6 kiloPascals (kPa) within 6 months of Screening or during the Screening Period.
Exclusion criteria
1. HCV genotype performed during screening indicating unable to genotype or infection with any other HCV genotype. 2. Positive test result at Screening for Hepatitis B surface antigen (HBsAg), or hepatitis B virus (HBV) DNA \> Lower Limit of Quantification (LLOQ) if HBsAg negative, or anti-Human Immunodeficiency virus antibody (HIV Ab). 3. Use of known strong inducers of cytochrome P450 3A (CYP3A) or strong inhibitors of CYP2C8 within 2 weeks or within 10 half-lives, whichever is longer, of the respective medication/supplement prior to study drug administration. 4. Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation including ascites (noted on physical exam), variceal bleeding, or hepatic encephalopathy. 5. Serum Alpha-Fetoprotein (sAFP) \> 100 ng/mL at Screening. 6. Confirmed presence of hepatocellular carcinoma (HCC) indicated on imaging techniques such as computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to Screening or on an ultrasound performed at Screening (a positive ultrasound result should be confirmed with CT scan or MRI.) 7. Any primary cause of liver disease other than chronic HCV-infection, including but not limited to the following: * Hemochromatosis * Alpha-1 antitrypsin deficiency * Wilson's disease * Autoimmune hepatitis * Alcoholic liver disease * Drug-related liver disease Steatosis and steatohepatitis on a liver biopsy coincident with HCV-related changes would not be considered exclusionary unless the steatohepatitis is considered to be the primary cause of the liver disease. 8. Screening laboratory analyses showing abnormal kidney, hepatic, or hematologic function.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) | 12 weeks after last dose of study drug | SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) at 12 weeks following therapy. 95% confidence interval (CI) is calculated using Wilson's score method. The lower bound of the 95% CI for the percentage of participants with SVR12 must exceed 67% to achieve superiority. |
| Percentage of Participants Achieving Sustained Virologic Response 24 Weeks Post-Treatment (SVR24) | 24 weeks after last dose of study drug | SVR24 is defined as HCV RNA less than the LLOQ at 24 weeks following therapy. 95% CI is calculated using Wilson's score method. The lower bound of the 95% CI for the percentage of participants with SVR12 must exceed 67% to achieve superiority. SVR24 is primary outcome measure only for China. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On Treatment Virologic Failure | Within 12 weeks after first dose of study drug | On treatment virologic failure is defined as confirmed HCV RNA greater than or equal to the LLOQ at any point during treatment after HCV RNA less than LLOQ, confirmed increase from the lowest value post-baseline in HCV RNA (two consecutive HCV RNA measurements greater than 1 log10 IU/mL above the lowest value post-baseline) at any time point during treatment, or HCV RNA greater than or equal to LLOQ persistently during treatment with at least 6 weeks (greater than or equal to 36 days) of treatment. 95% CI is calculated using Wilson's score method. |
| Percentage of Participants With Virologic Relapse | Within 12 weeks after the last dose of study drug | Virologic relapse is defined as confirmed HCV RNA greater than or equal to LLOQ between end of treatment and 12 weeks after the last dose of study drugs among participants completing treatment and with HCV RNA less than LLOQ at the end of treatment. Completion of treatment is defined as a study drug duration greater than or equal to 77 days. 95% CI is calculated using Wilson's score method. |
| Percentage of Participants With Virologic Relapse by Post-Treatment Week 24 | Within 24 weeks after the last dose of study drug | Virologic relapse is defined as confirmed HCV RNA greater than or equal to LLOQ between end of treatment and 24 weeks after the last dose of study drugs among participants completing treatment and with HCV RNA less than LLOQ at the end of treatment. Completion of treatment is defined as a study drug duration greater than or equal to 77 days. 95% CI is calculated using Wilson's score method. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABT-450/r/ABT-267 + ABT-333 + Ribavirin ABT-450/r/ABT-267 once daily + ABT-333 twice daily + weight-based RBV divided twice daily for 12 weeks | 104 |
| Total | 104 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | ABT-450/r/ABT-267 + ABT-333 + Ribavirin |
|---|---|
| Age, Continuous | 56.43 years STANDARD_DEVIATION 8.11 |
| Region of Enrollment China | 63 participants |
| Region of Enrollment South Korea | 21 participants |
| Region of Enrollment Taiwan | 20 participants |
| Sex: Female, Male Female | 64 Participants |
| Sex: Female, Male Male | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 104 |
| other Total, other adverse events | 71 / 104 |
| serious Total, serious adverse events | 4 / 104 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-Treatment (SVR12)
SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) at 12 weeks following therapy. 95% confidence interval (CI) is calculated using Wilson's score method. The lower bound of the 95% CI for the percentage of participants with SVR12 must exceed 67% to achieve superiority.
Time frame: 12 weeks after last dose of study drug
Population: Intent-to-Treat Population: all enrolled participants who received at least one dose of study drug. Participants with missing data were imputed as failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 + ABT-333 + Ribavirin | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) | 100 percentage of participants |
Primary
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks Post-Treatment (SVR24)
SVR24 is defined as HCV RNA less than the LLOQ at 24 weeks following therapy. 95% CI is calculated using Wilson's score method. The lower bound of the 95% CI for the percentage of participants with SVR12 must exceed 67% to achieve superiority. SVR24 is primary outcome measure only for China.
Time frame: 24 weeks after last dose of study drug
Population: Intent-to-Treat Population: all enrolled participants who received at least one dose of study drug. Participants with missing data were imputed as failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 + ABT-333 + Ribavirin | Percentage of Participants Achieving Sustained Virologic Response 24 Weeks Post-Treatment (SVR24) | 100 percentage of participants |
Secondary
Percentage of Participants With On Treatment Virologic Failure
On treatment virologic failure is defined as confirmed HCV RNA greater than or equal to the LLOQ at any point during treatment after HCV RNA less than LLOQ, confirmed increase from the lowest value post-baseline in HCV RNA (two consecutive HCV RNA measurements greater than 1 log10 IU/mL above the lowest value post-baseline) at any time point during treatment, or HCV RNA greater than or equal to LLOQ persistently during treatment with at least 6 weeks (greater than or equal to 36 days) of treatment. 95% CI is calculated using Wilson's score method.
Time frame: Within 12 weeks after first dose of study drug
Population: Intent-to-Treat Population: all enrolled participants who received at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 + ABT-333 + Ribavirin | Percentage of Participants With On Treatment Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants With Virologic Relapse
Virologic relapse is defined as confirmed HCV RNA greater than or equal to LLOQ between end of treatment and 12 weeks after the last dose of study drugs among participants completing treatment and with HCV RNA less than LLOQ at the end of treatment. Completion of treatment is defined as a study drug duration greater than or equal to 77 days. 95% CI is calculated using Wilson's score method.
Time frame: Within 12 weeks after the last dose of study drug
Population: Intent-to-Treat Population: all enrolled participants who received at least one dose of study drug. Only completers (ie, participants who were dosed with study drug at least 77 days) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 + ABT-333 + Ribavirin | Percentage of Participants With Virologic Relapse | 0 percentage of participants |
Secondary
Percentage of Participants With Virologic Relapse by Post-Treatment Week 24
Virologic relapse is defined as confirmed HCV RNA greater than or equal to LLOQ between end of treatment and 24 weeks after the last dose of study drugs among participants completing treatment and with HCV RNA less than LLOQ at the end of treatment. Completion of treatment is defined as a study drug duration greater than or equal to 77 days. 95% CI is calculated using Wilson's score method.
Time frame: Within 24 weeks after the last dose of study drug
Population: Intent-to-Treat Population: all enrolled participants who received at least one dose of study drug. Only completers (ie, participants who were dosed with study drug at least 77 days) were included.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r/ABT-267 + ABT-333 + Ribavirin | Percentage of Participants With Virologic Relapse by Post-Treatment Week 24 | 0 percentage of participants |