Chronic Hepatitis C, Hepatitis C Virus, Compensated Cirrhosis
Conditions
Keywords
Chronic Hepatitis C, Cirrhosis, Child Pugh A, Hepatitis C virus, Compensated Cirrhosis, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Cirrhotic
Brief summary
The purpose of this study is to evaluate the safety and antiviral effect of multiple doses of ABT-493 and ABT-530 in adults with genotype 1 HCV.
Interventions
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Chronic HCV infection prior to study enrollment. * Screening laboratory result indicating HCV genotype 1-infection. * Subject has plasma HCV RNA level greater than 10,000 IU/mL at Screening. * Per local standard, subject is considered to be non-cirrhotic or to have compensated cirrhosis.
Exclusion criteria
* History of severe, life-threatening or other significant sensitivity to any drug. * Positive test result for Hepatitis B surface antigen (HBsAg) or anti-Human Immunodeficiency Virus antibody (HIV Ab). * Prior therapy for the treatment of HCV. * Any current or past clinical evidence of Child Pugh B or C classification of clinical history of liver decompensation including ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy. * Any cause of liver disease other than chronic HCV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | Day 1 through prior to first dose of the combination regimen on Study Day 4 | Maximal decrease from baseline in log10 HCV RNA levels during ABT-493 or ABT-530 monotherapy treatment. The baseline value was the last measurement before the first dose of monotherapy on Day 1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 12 weeks after last actual dose of combination study drug | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of combination study drug. |
| Percentage of Participants With On-treatment Virologic Failure | Up to 87 days | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during combination treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during combination treatment; or HCV RNA ≥ LLOQ at end of combination treatment with at least 6 weeks of combination treatment. |
| Percentage of Participants With Post-treatment Relapse | From the end of treatment through 12 weeks after the last dose of combination study drug | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants completing combination treatment with HCV RNA levels \< LLOQ at the end of treatment. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 Non-cirrhotic ABT-493 Dose A (100 mg once daily \[QD\]) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 2 Non-cirrhotic ABT-493 Dose B (400 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 3 Non-cirrhotic ABT-493 Dose C (700 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 9 |
| Arm 4 Non-cirrhotic ABT-493 Dose D (200 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 5 Compensated Cirrhotic ABT-493 Dose E (200 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 6 Non-cirrhotic ABT-530 Dose A (15 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 7 Non-cirrhotic ABT-530 Dose B (120 mg QD) for 3 days,followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 8 Non-cirrhotic ABT-530 Dose C (400 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 9 Non-cirrhotic ABT-530 Dose D (40 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 10 Compensated Cirrhotic ABT-530 Dose E (120 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 11 Non-cirrhotic ABT-493 Dose F (300 mg QD) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 8 |
| Arm 12 Non-cirrhotic ABT-530 Dose F (≤ 400 mg) for 3 days, followed by ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks | 0 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Incarcerated | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 |
| Overall Study | Moved | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Arm 1 Non-cirrhotic | Arm 2 Non-cirrhotic | Arm 3 Non-cirrhotic | Arm 4 Non-cirrhotic | Arm 5 Compensated Cirrhotic | Arm 6 Non-cirrhotic | Arm 7 Non-cirrhotic | Arm 8 Non-cirrhotic | Arm 9 Non-cirrhotic | Arm 10 Compensated Cirrhotic | Arm 11 Non-cirrhotic | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 5.2 | 55.8 years STANDARD_DEVIATION 9.53 | 50.3 years STANDARD_DEVIATION 9.04 | 52.6 years STANDARD_DEVIATION 6.37 | 58.6 years STANDARD_DEVIATION 6.14 | 53.9 years STANDARD_DEVIATION 9.34 | 50.6 years STANDARD_DEVIATION 12.6 | 49.4 years STANDARD_DEVIATION 15.31 | 60.5 years STANDARD_DEVIATION 5.61 | 55.3 years STANDARD_DEVIATION 9.63 | 54.6 years STANDARD_DEVIATION 5.15 | 54.1 years STANDARD_DEVIATION 9.17 |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 0 Participants | 3 Participants | 1 Participants | 3 Participants | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 4 Participants | 23 Participants |
| Sex: Female, Male Male | 5 Participants | 6 Participants | 9 Participants | 5 Participants | 7 Participants | 5 Participants | 8 Participants | 6 Participants | 6 Participants | 5 Participants | 4 Participants | 66 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 8 | 7 / 8 | 7 / 9 | 8 / 8 | 7 / 8 | 7 / 8 | 8 / 8 | 4 / 8 | 5 / 8 | 7 / 8 | 7 / 8 |
| serious Total, serious adverse events | 1 / 8 | 0 / 8 | 0 / 9 | 0 / 8 | 1 / 8 | 0 / 8 | 0 / 8 | 1 / 8 | 1 / 8 | 0 / 8 | 0 / 8 |
Outcome results
Primary
Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment
Maximal decrease from baseline in log10 HCV RNA levels during ABT-493 or ABT-530 monotherapy treatment. The baseline value was the last measurement before the first dose of monotherapy on Day 1.
Time frame: Day 1 through prior to first dose of the combination regimen on Study Day 4
Population: Monotherapy Analysis Sets for Substudy 1 (Arms 1-5, 11) and SubStudy 2 (Arms 6-10, 12) are defined as all participants who received at least 1 dose of monotherapy and have a baseline and at least 1 postbaseline measurement of HCV RNA during monotherapy. Data for subjects who received the same treatment (Arms 4+5; Arms 7+10) were analyzed together.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1 Non-cirrhotic | Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | -4.11 Log10 IU/mL | Standard Deviation 0.47 |
| Arm 2 Non-cirrhotic | Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | -4.02 Log10 IU/mL | Standard Deviation 0.66 |
| Arm 3 Non-cirrhotic | Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | -4.31 Log10 IU/mL | Standard Deviation 0.26 |
| Arm 4 Non-cirrhotic + Arm 5 Compensated Cirrhotic | Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | -4.06 Log10 IU/mL | Standard Deviation 0.56 |
| Arm 6 Non-cirrhotic | Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | -3.38 Log10 IU/mL | Standard Deviation 0.77 |
| Arm 7 Non-cirrhotic + Arm 10 Compensated Cirrhotic | Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | -4.21 Log10 IU/mL | Standard Deviation 0.42 |
| Arm 8 Non-cirrhotic | Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | -4.25 Log10 IU/mL | Standard Deviation 0.49 |
| Arm 9 Non-cirrhotic | Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | -4.08 Log10 IU/mL | Standard Deviation 0.45 |
| Arm 11 Non-cirrhotic | Maximal Decrease From Baseline in log10 HCV RNA Levels During ABT-493 or ABT-530 Monotherapy Treatment | -3.79 Log10 IU/mL | Standard Deviation 1.21 |
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during combination treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during combination treatment; or HCV RNA ≥ LLOQ at end of combination treatment with at least 6 weeks of combination treatment.
Time frame: Up to 87 days
Population: Combination Treatment Analysis Set: all participants who receive at least 1 dose of the combination regimen of ABT-450/r/ABT-267 + ABT-333 + RBV.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 Non-cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
| Arm 2 Non-cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
| Arm 3 Non-cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
| Arm 4 Non-cirrhotic + Arm 5 Compensated Cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
| Arm 6 Non-cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
| Arm 7 Non-cirrhotic + Arm 10 Compensated Cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
| Arm 8 Non-cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 12.5 participants |
| Arm 9 Non-cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
| Arm 11 Non-cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
| Arm 12 Non-cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
| Arm 11 Non-cirrhotic | Percentage of Participants With On-treatment Virologic Failure | 0 participants |
Secondary
Percentage of Participants With Post-treatment Relapse
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants completing combination treatment with HCV RNA levels \< LLOQ at the end of treatment.
Time frame: From the end of treatment through 12 weeks after the last dose of combination study drug
Population: Combination Treatment Analysis Set: all participants who receive at least 1 dose of the combination regimen of ABT-450/r/ABT-267 + ABT-333 + RBV, completed treatment, and had HCV RNA \<LLOQ at the final treatment visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 Non-cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 2 Non-cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 3 Non-cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 4 Non-cirrhotic + Arm 5 Compensated Cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 6 Non-cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 7 Non-cirrhotic + Arm 10 Compensated Cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 8 Non-cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 9 Non-cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 11 Non-cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 12 Non-cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm 11 Non-cirrhotic | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of combination study drug.
Time frame: 12 weeks after last actual dose of combination study drug
Population: Combination Treatment Analysis Set: all participants who receive at least 1 dose of the combination regimen of ABT-450/r/ABT-267 + ABT-333 + RBV; participants with missing data after backwards imputation were counted as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 Non-cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 87.5 percentage of participants |
| Arm 2 Non-cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm 3 Non-cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 87.5 percentage of participants |
| Arm 4 Non-cirrhotic + Arm 5 Compensated Cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm 6 Non-cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm 7 Non-cirrhotic + Arm 10 Compensated Cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm 8 Non-cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 87.5 percentage of participants |
| Arm 9 Non-cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 87.5 percentage of participants |
| Arm 11 Non-cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm 12 Non-cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm 11 Non-cirrhotic | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |