Chronic Hepatitis C Infection, Hepatitis C, Hepatitis C Virus
Conditions
Brief summary
The purpose of this study is to evaluate the antiviral activity, safety, and pharmacokinetics of ABT-450 with ritonavir (ABT-450/r) dosed in combination with ABT-333 (also known as dasabuvir) and ribavirin (RBV) in treatment-naïve and non responder participants with genotype 1 chronic hepatitis C virus (HCV) infection.
Detailed description
This was a phase 2a multicenter, open-label, sequential, 3-arm, combination treatment study of a regimen of ABT-450/r/ABT-333, and ribavirin (RBV) in hepatitis C virus (HCV) genotype 1-infected treatment-naïve participants and previous non-responders to pegylated interferon (pegIFN)/RBV treatment.
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis C virus (HCV) * Treatment naive, null or partial responders to previous treatment with peginterferon and ribavirin * Males and females 18-65 years old * Body mass index 18 to \< 35 kg/m\^2 * Females must be postmenopausal for at least 2 years or surgically sterile
Exclusion criteria
* Cirrhosis or extensive bridging fibrosis * History of cardiac disease * Positive screen for certain drugs or alcohol * Abnormal laboratory results * Significant sensitivity to any drug * Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody * Use of strong cytochrome P450 3A (CYP3A), cytochrome P450 2C8 (CYP2C8), and organic anion transporting polypeptide 1B1 (OATP1B1) enzyme inducers or inhibitors within 1 month of dosing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Detection (LLOD) From Week 4 Through Week 12 | Week 4 through Week 12 | Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of detection (\< 15 IU/mL). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HCV RNA Below the Lower Limit of Quantitation (LLOQ; <25 IU/mL) at Week 4 | Week 4 | Analysis of percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (\< 25 IU/mL). |
| Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment | Post-treatment Day 1 to Post-treatment Week 12 | Sustained virologic response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; \< 25 IU/mL) 12 weeks after the last dose of study drug. |
| Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment | Post-treatment Day 1 to Post-treatment Week 24 | Sustained virologic response 24 (SVR24) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; \< 25 IU/mL) 24 weeks after the last dose of study drug. |
| Time to Failure to Suppress or Rebound During Treatment | Day 1 through Week 12 | Time to failure to achieve a 2 log10 IU/mL HCV RNA decrease at Week 1, failure to achieve HCV RNA \< Lower Limit of Detection (LLOD) at Week 6, or a confirmed increase of at least 0.5 log10 IU/mL above nadir (local minimum value) or confirmed HCV RNA \> lower limit of quantitation (LLOQ) for participants who previously achieved HCV RNA \< LLOQ. |
| Time to Virologic Relapse Post-treatment | Post-treatment Day 1 to post-treatment week 48 | Time to the first of 2 consecutive measurements of confirmed HCV RNA ≥ lower limit of quantitation (LLOQ) at any point in the post-treatment period among participants with HCV RNA \< LLOQ at the end of treatment. |
| Percentage of Participants With HCV RNA < 1000 International Units Per Milliliter (IU/mL) | Week 2 | Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2. |
| Pharmacokinetics (C Trough) of ABT 450 in HCV Infected Participants | Day 1 to Week 12 | Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose. |
| Pharmacokinetics (C Trough) of ABT-333 in HCV Infected Participants | Day 1 to Week 12 | Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose. |
| Pharmacokinetics (C Trough) of Ritonavir in HCV Infected Participants | Day 1 to Week 12 | Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose. |
| Pharmacokinetics (C Trough) of Ribavirin in HCV Infected Participants | Day 1 to Week 12 | Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose. |
| Resistance-Associated Variants and Phenotypic Resistance | Day 1 to post-treatment week 48 | Baseline samples were analyzed for resistance-associated amino acid variants using population sequencing. Phenotypic resistance to ABT-450 or ABT-333 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Participants not achieving SVR12 were analyzed for resistance-associated variants at the time of failure using population sequencing and were compared with the baseline and appropriate reference sequences to assess amino acid changes. Phenotypic resistance to ABT-450 or ABT-333 at the time of failure was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance at baseline and at the time of failure are presented. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve ABT-450/r (250/100 mg) once daily (QD) and ABT-333 (400 mg) twice daily (BID) plus weight-based ribavirin (RBV) divided BID for 12 weeks in treatment-naïve participants. | 19 |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve ABT-450/r (150/100 mg) once daily (QD) and ABT-333 (400 mg) twice daily (BID) plus weight-based ribavirin (RBV) divided BID for 12 weeks in treatment-naïve participants. | 14 |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders ABT-450/r (150/100 mg) once daily (QD) and ABT-333 (400 mg) twice daily (BID) plus weight-based ribavirin (RBV) divided BID in previous non-responders to pegylated interferon (pegIFN) and RBV. | 17 |
| Total | 50 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Non-compliance | 0 | 1 | 0 |
| Overall Study | Virologic Failure | 0 | 0 | 5 |
Baseline characteristics
| Characteristic | ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Total |
|---|---|---|---|---|
| Age, Continuous | 53.6 years STANDARD_DEVIATION 9.78 | 50.9 years STANDARD_DEVIATION 10.45 | 52.3 years STANDARD_DEVIATION 9.03 | 52.4 years STANDARD_DEVIATION 9.59 |
| Hepatitis C Virus (HCV) Genotype/ Subtype 1A | 17 participants | 11 participants | 16 participants | 44 participants |
| Hepatitis C Virus (HCV) Genotype/ Subtype 1B | 2 participants | 3 participants | 1 participants | 6 participants |
| Interleukin 28B (IL28B) Genotype CC | 10 participants | 5 participants | 0 participants | 15 participants |
| Interleukin 28B (IL28B) Genotype CT | 7 participants | 7 participants | 12 participants | 26 participants |
| Interleukin 28B (IL28B) Genotype TT | 2 participants | 2 participants | 5 participants | 9 participants |
| Sex: Female, Male Female | 9 Participants | 0 Participants | 6 Participants | 15 Participants |
| Sex: Female, Male Male | 10 Participants | 14 Participants | 11 Participants | 35 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 | 17 / 19 | 13 / 14 | 13 / 17 |
| serious Total, serious adverse events | 0 / 19 | 0 / 14 | 0 / 17 |
Outcome results
Primary
Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Detection (LLOD) From Week 4 Through Week 12
Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of detection (\< 15 IU/mL).
Time frame: Week 4 through Week 12
Population: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT). Participants with missing data were imputed as failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Detection (LLOD) From Week 4 Through Week 12 | 89.5 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Detection (LLOD) From Week 4 Through Week 12 | 78.6 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Detection (LLOD) From Week 4 Through Week 12 | 58.8 percentage of participants |
Comparison: For the percentage of subjects with HCV RNA suppressed below the LLOD from Week 4 through Week 12, if it was assumed that 60% of subjects would be successfully suppressed from Week 4 through Week 12, then 20 subjects in arm 1 would give a 95% 2-sided confidence interval (CI) of (38.5%, 81.5%), 10 subjects in arm 2 would give a 95% CI of (29.6%, 90.4%), and 15 subjects in arm 3 would give a 95% CI of (35.2%, 84.8%) for the percentage of subjects suppressed using the binomial exact method.p-value: 0.547Regression, Logistic
p-value: 0.207Regression, Logistic
Secondary
Percentage of Participants With HCV RNA < 1000 International Units Per Milliliter (IU/mL)
Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2.
Time frame: Week 2
Population: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT). Participants with missing data were imputed as failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With HCV RNA < 1000 International Units Per Milliliter (IU/mL) | 100 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With HCV RNA < 1000 International Units Per Milliliter (IU/mL) | 92.9 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Percentage of Participants With HCV RNA < 1000 International Units Per Milliliter (IU/mL) | 100 percentage of participants |
p-value: 0.061Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With HCV RNA Below the Lower Limit of Quantitation (LLOQ; <25 IU/mL) at Week 4
Analysis of percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (\< 25 IU/mL).
Time frame: Week 4
Population: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT). Participants with missing data were imputed as failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With HCV RNA Below the Lower Limit of Quantitation (LLOQ; <25 IU/mL) at Week 4 | 100 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With HCV RNA Below the Lower Limit of Quantitation (LLOQ; <25 IU/mL) at Week 4 | 92.9 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Percentage of Participants With HCV RNA Below the Lower Limit of Quantitation (LLOQ; <25 IU/mL) at Week 4 | 88.2 percentage of participants |
p-value: 0.061Cochran-Mantel-Haenszel
p-value: 0.375Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment
Sustained virologic response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; \< 25 IU/mL) 12 weeks after the last dose of study drug.
Time frame: Post-treatment Day 1 to Post-treatment Week 12
Population: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT). Participants with missing data were imputed as failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment | 94.7 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment | 92.9 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment | 47.1 percentage of participants |
p-value: 0.312Cochran-Mantel-Haenszel
p-value: 0.012Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment
Sustained virologic response 24 (SVR24) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; \< 25 IU/mL) 24 weeks after the last dose of study drug.
Time frame: Post-treatment Day 1 to Post-treatment Week 24
Population: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT). Participants with missing data were imputed as failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment | 94.7 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment | 85.7 percentage of participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment | 47.1 percentage of participants |
p-value: 0.312Cochran-Mantel-Haenszel
p-value: 0.012Cochran-Mantel-Haenszel
Secondary
Pharmacokinetics (C Trough) of ABT-333 in HCV Infected Participants
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Time frame: Day 1 to Week 12
Population: Pharmacokinetic analyses included all participants who received at least 1 dose of the study drug (ITT) and for whom concentration data was available to characterize C trough.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Pharmacokinetics (C Trough) of ABT-333 in HCV Infected Participants | 148.44 nanograms (ng) per milliliter (mL) |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Pharmacokinetics (C Trough) of ABT-333 in HCV Infected Participants | 162.57 nanograms (ng) per milliliter (mL) |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Pharmacokinetics (C Trough) of ABT-333 in HCV Infected Participants | 166.15 nanograms (ng) per milliliter (mL) |
Secondary
Pharmacokinetics (C Trough) of ABT 450 in HCV Infected Participants
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Time frame: Day 1 to Week 12
Population: Pharmacokinetic analyses included all participants who received at least 1 dose of the study drug (ITT) and for whom concentration data was available to characterize C trough.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Pharmacokinetics (C Trough) of ABT 450 in HCV Infected Participants | 53.21 nanograms (ng) per milliliter (mL) |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Pharmacokinetics (C Trough) of ABT 450 in HCV Infected Participants | 16.81 nanograms (ng) per milliliter (mL) |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Pharmacokinetics (C Trough) of ABT 450 in HCV Infected Participants | 16.15 nanograms (ng) per milliliter (mL) |
Secondary
Pharmacokinetics (C Trough) of Ribavirin in HCV Infected Participants
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Time frame: Day 1 to Week 12
Population: Pharmacokinetic analyses included all participants who received at least 1 dose of the study drug (ITT) and for whom concentration data was available to characterize C trough.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Pharmacokinetics (C Trough) of Ribavirin in HCV Infected Participants | 2480 nanograms (ng) per milliliter (mL) |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Pharmacokinetics (C Trough) of Ribavirin in HCV Infected Participants | 2280 nanograms (ng) per milliliter (mL) |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Pharmacokinetics (C Trough) of Ribavirin in HCV Infected Participants | 2000 nanograms (ng) per milliliter (mL) |
Secondary
Pharmacokinetics (C Trough) of Ritonavir in HCV Infected Participants
Trough concentration (C trough) is the concentration 24 hours after once daily (QD) dose and 12 hours after twice daily (BID) dose.
Time frame: Day 1 to Week 12
Population: Pharmacokinetic analyses included all participants who received at least 1 dose of the study drug (ITT) and for whom concentration data was available to characterize C trough.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Pharmacokinetics (C Trough) of Ritonavir in HCV Infected Participants | 43.92 nanograms (ng) per milliliter (mL) |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Pharmacokinetics (C Trough) of Ritonavir in HCV Infected Participants | 42.35 nanograms (ng) per milliliter (mL) |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Pharmacokinetics (C Trough) of Ritonavir in HCV Infected Participants | 44.21 nanograms (ng) per milliliter (mL) |
Secondary
Resistance-Associated Variants and Phenotypic Resistance
Baseline samples were analyzed for resistance-associated amino acid variants using population sequencing. Phenotypic resistance to ABT-450 or ABT-333 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Participants not achieving SVR12 were analyzed for resistance-associated variants at the time of failure using population sequencing and were compared with the baseline and appropriate reference sequences to assess amino acid changes. Phenotypic resistance to ABT-450 or ABT-333 at the time of failure was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance at baseline and at the time of failure are presented.
Time frame: Day 1 to post-treatment week 48
Population: Resistance analyses included all participants who receive at least one dose of study drug (intent-to-treat \[ITT\] population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Baseline Variants in NS3; n=49 | 0 participants |
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Baseline Resistance to ABT-450 >10-fold; n=40 | 0 participants |
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Baseline Variants in NS5B; n=49 | 2 participants |
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Baseline Resistance to ABT-333 >10-fold; n=49 | 0 participants |
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistant variants in NS3; n=11 | 0 participants |
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistance to ABT-450 >10-fold; n=9 | 0 participants |
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistant variants in NS5B; n=11 | 0 participants |
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistance to ABT-333 >10-fold;n=11 | 0 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Baseline Variants in NS5B; n=49 | 2 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistant variants in NS5B; n=11 | 0 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Baseline Resistance to ABT-333 >10-fold; n=49 | 1 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistant variants in NS3; n=11 | 0 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistance to ABT-450 >10-fold; n=9 | 0 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Baseline Variants in NS3; n=49 | 0 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Baseline Resistance to ABT-450 >10-fold; n=40 | 0 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistance to ABT-333 >10-fold;n=11 | 0 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Resistance-Associated Variants and Phenotypic Resistance | Baseline Variants in NS5B; n=49 | 0 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Resistance-Associated Variants and Phenotypic Resistance | Baseline Resistance to ABT-450 >10-fold; n=40 | 1 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Resistance-Associated Variants and Phenotypic Resistance | Baseline Variants in NS3; n=49 | 1 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Resistance-Associated Variants and Phenotypic Resistance | Baseline Resistance to ABT-333 >10-fold; n=49 | 0 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistant variants in NS5B; n=11 | 8 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistance to ABT-450 >10-fold; n=9 | 6 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistant variants in NS3; n=11 | 8 participants |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Resistance-Associated Variants and Phenotypic Resistance | Post-treatment resistance to ABT-333 >10-fold;n=11 | 8 participants |
Secondary
Time to Failure to Suppress or Rebound During Treatment
Time to failure to achieve a 2 log10 IU/mL HCV RNA decrease at Week 1, failure to achieve HCV RNA \< Lower Limit of Detection (LLOD) at Week 6, or a confirmed increase of at least 0.5 log10 IU/mL above nadir (local minimum value) or confirmed HCV RNA \> lower limit of quantitation (LLOQ) for participants who previously achieved HCV RNA \< LLOQ.
Time frame: Day 1 through Week 12
Population: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Time to Failure to Suppress or Rebound During Treatment | 43.0 days | — |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Time to Failure to Suppress or Rebound During Treatment | NA days | — |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Time to Failure to Suppress or Rebound During Treatment | 62.6 days | Standard Error 5.44 |
p-value: 0.395Log Rank
p-value: 0.01Log Rank
Secondary
Time to Virologic Relapse Post-treatment
Time to the first of 2 consecutive measurements of confirmed HCV RNA ≥ lower limit of quantitation (LLOQ) at any point in the post-treatment period among participants with HCV RNA \< LLOQ at the end of treatment.
Time frame: Post-treatment Day 1 to post-treatment week 48
Population: All randomized participants who received at least 1 dose of study drug with HCV RNA \< LLOQ at the final treatment visit who completed treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-450/r (250/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Time to Virologic Relapse Post-treatment | NA days | — |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Treatment-naïve | Time to Virologic Relapse Post-treatment | NA days | — |
| ABT-450/r (150/100 mg) and ABT-333 Plus RBV in Non-responders | Time to Virologic Relapse Post-treatment | 15.8 days | Standard Error 0.21 |
p-value: 0.048Log Rank