Chronic Hepatitis C Infection
Conditions
Keywords
Hepatitis C,Genotype 1
Brief summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and antiviral activity of multiple, ascending doses of ABT-267 (also known as ombitasvir) administered as two-day monotherapy followed by ABT-267 in combination therapy with other direct-acting antiviral agents (DAAs) ABT-450 with ritonavir (ABT-450/r) and ABT-333 (also known as dasabuvir) plus ribavirin (RBV) in patients with chronic Hepatitis C virus (HCV) infection without cirrhosis.
Detailed description
An open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of ABT-267 as monotherapy for 2 days, followed by ABT-267, ABT-450 with ritonavir (ABT-450/r) and ABT-333 plus ribavirin (RBV) combination therapy for 12 weeks in treatment-naïve, non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. The study included post-treatment follow-up for 48 weeks.
Interventions
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 70 Years
Healthy volunteers
No
Inclusion criteria
* Male or female between the age of 18 and 70 years, inclusive, at time of enrollment. * Subject has never received antiviral treatment for hepatitis C virus (HCV) infection. * Body mass index (BMI) is ≥ 18 to \< 38 kg/m\^2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m). * Chronic HCV genotype 1-infection for at least 6 months prior to study enrollment. * Subject has plasma HCV RNA level \> 10,000 IU/mL at screening
Exclusion criteria
* History of severe, life-threatening or other significant sensitivity to any drug. * Females who are or plan to become pregnant or breastfeeding or males whose partner is pregnant or planning to become pregnant. * Recent history of drug or alcohol abuse that could preclude adherence to the protocol. * Positive test result for hepatitis B surface antigen or anti-human immunodeficiency virus (HIV) antibodies. * Any current or past clinical evidence of cirrhosis (e.g., ascites, esophageal varices), or a liver biopsy or FibroTest/aspartate aminotransferase to platelet ratio (APRI) or FibroScan® showing cirrhosis or extensive bridging fibrosis.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy | Pre-dose on Days 1, 2, and 3 | The baseline value was the last measurement before the first dose of ABT-267 monotherapy (Day 1). The maximal decrease during monotherapy was the change from baseline to the lowest log10 IU/mL HCV RNA level any time from the first dose of ABT-267 on Day 1 to the last log10 HCV RNA level before the first dose of ABT-267 combination therapy (Study Day 3). |
| Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1 | Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose) | Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was estimated using noncompartmental analyses. |
| Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1 | Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose) | Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Time of maximum plasma concentration (Tmax; measured in hours) was estimated using noncompartmental analyses. |
| Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1 | Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose) | Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC\[24\]; measured in ng multiplied by hour/mL) was estimated using noncompartmental analyses. |
| Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3 | Day 2 (pre-dose) and Day 3 (pre-dose) | Blood samples were collected pre-dose on Day 2 (prior to second dose of ABT-267 monotherapy) and pre-dose on Day 3 (prior to first dose of combination therapy). The samples were analyzed for ABT-267 using validated analytical methods. Pre-dose plasma concentrations on Day 2 and Day 3 (Ctrough, measured in ng/mL) are reported. |
| Number of Participants With Adverse Events (AEs) | All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks). | An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs), and rated the severity of each event as either: Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening. A serious adverse event was any event that resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy | 12 and 24 weeks after last dose of combination study drug | The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 and 24 weeks after the last dose of combination study drug. The LLOQ for the assay was 25 IU/mL. |
| Percentage of Participants With Rapid Virologic Response | 4 weeks | The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation \[\< LLOQ\]) after 4 weeks of combination therapy. |
| Percentage of Participants With End-of-Treatment Response | 12 weeks | The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation \[\< LLOQ\]) at the end of combination therapy (12 weeks). |
| Percentage of Participants With Extended Rapid Virologic Response | Weeks 4 to 12 | The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation \[\< LLOQ\]) at Weeks 4 through 12 of combination therapy. |
| Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy | Predose on Days 1, 2, and 3 | The relationship between ABT-267 dose, ABT-267 concentration, and response was analyzed as the change in viral load (measured as log10 IU/mL) from baseline (pre-dose on Day 1) to pre-dose on Days 2 and 3. Plasma concentrations of ABT-267 pre-dose on Days 2 and 3 are presented above in 4. Primary Outcome: Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Resistance-Associated Variants and Phenotypic Resistance | Day 1 Pre-dose (Baseline) and Day 3 Pre-dose | Baseline (pre-dose on Day 1) samples were analyzed for resistance-associated amino acid (AA) variants using population sequencing. Phenotypic resistance to ABT-267 at Baseline was assessed by calculating the fold difference in the the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Day 3 samples were analyzed using population sequencing and were compared with the baseline and appropriate prototypic reference sequences to assess AA changes. Phenotypic resistance at Day 3 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 AA positions and phenotypic resistance at Baseline and Day 3 are presented. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks | 6 |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks | 6 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Total |
|---|---|---|---|
| Age, Continuous | 51.5 years STANDARD_DEVIATION 4.76 | 46.8 years STANDARD_DEVIATION 11.84 | 49.2 years STANDARD_DEVIATION 8.94 |
| Sex: Female, Male Female | 4 Participants | 3 Participants | 7 Participants |
| Sex: Female, Male Male | 2 Participants | 3 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 3 / 6 | 5 / 6 |
| serious Total, serious adverse events | 0 / 6 | 2 / 6 |
Outcome results
Primary
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC\[24\]; measured in ng multiplied by hour/mL) was estimated using noncompartmental analyses.
Time frame: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
Population: All participants who received at least one dose of study drug (ITT population).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1 | 18.0 ng*hr/mL | Standard Deviation 2.46 |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1 | 467 ng*hr/mL | Standard Deviation 236 |
Primary
Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was estimated using noncompartmental analyses.
Time frame: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
Population: All participants who received at least one dose of study drug (intent-to-treat \[ITT\] population).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1 | 1.66 ng/mL | Standard Deviation 0.21 |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1 | 41.0 ng/mL | Standard Deviation 16.5 |
Primary
Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy
The baseline value was the last measurement before the first dose of ABT-267 monotherapy (Day 1). The maximal decrease during monotherapy was the change from baseline to the lowest log10 IU/mL HCV RNA level any time from the first dose of ABT-267 on Day 1 to the last log10 HCV RNA level before the first dose of ABT-267 combination therapy (Study Day 3).
Time frame: Pre-dose on Days 1, 2, and 3
Population: All participants who received at least one dose of study drug (ITT population).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy | -1.6 log10 IU/mL | Standard Error 0.41 |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy | -3.1 log10 IU/mL | Standard Error 0.41 |
p-value: 0.03595% CI: [-2.81, -0.13]ANCOVA
Primary
Number of Participants With Adverse Events (AEs)
An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs), and rated the severity of each event as either: Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening. A serious adverse event was any event that resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention.
Time frame: All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks).
Population: All participants who received at least one dose of study drug (safety population).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE | 3 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 0 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any serious AE | 0 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE leading to RBV dose modification | 0 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE at least possibly related to DAAs | 3 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any fatal AE | 0 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 0 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any severe AE | 0 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Deaths | 0 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE at least possibly related to DAAs | 4 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE | 5 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any severe AE | 1 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any serious AE | 2 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 1 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 0 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any AE leading to RBV dose modification | 1 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Number of Participants With Adverse Events (AEs) | Any fatal AE | 0 participants |
Primary
Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3
Blood samples were collected pre-dose on Day 2 (prior to second dose of ABT-267 monotherapy) and pre-dose on Day 3 (prior to first dose of combination therapy). The samples were analyzed for ABT-267 using validated analytical methods. Pre-dose plasma concentrations on Day 2 and Day 3 (Ctrough, measured in ng/mL) are reported.
Time frame: Day 2 (pre-dose) and Day 3 (pre-dose)
Population: All participants who received at least one dose of study drug (ITT population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3 | Day 2 Ctrough | 0 ng/mL | Standard Deviation 0 |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3 | Day 3 Ctrough | 0.228 ng/mL | Standard Deviation 0.263 |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3 | Day 2 Ctrough | 5.2 ng/mL | Standard Deviation 1.78 |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3 | Day 3 Ctrough | 6.62 ng/mL | Standard Deviation 3.77 |
Primary
Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Time of maximum plasma concentration (Tmax; measured in hours) was estimated using noncompartmental analyses.
Time frame: Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
Population: All participants who received at least one dose of study drug (ITT population).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1 | 3.67 hours | Standard Deviation 0.82 |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1 | 3.67 hours | Standard Deviation 1.5 |
Secondary
Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy
The relationship between ABT-267 dose, ABT-267 concentration, and response was analyzed as the change in viral load (measured as log10 IU/mL) from baseline (pre-dose on Day 1) to pre-dose on Days 2 and 3. Plasma concentrations of ABT-267 pre-dose on Days 2 and 3 are presented above in 4. Primary Outcome: Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3.
Time frame: Predose on Days 1, 2, and 3
Population: All participants who received at least one dose of study drug (ITT population).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy | Day 2 Mean change in Viral Load from Baseline | -1.95 log10 IU/mL | Standard Deviation 0.63 |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy | Day 3 Mean change in Viral Load from Baseline | -1.96 log10 IU/mL | Standard Deviation 0.405 |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy | Day 2 Mean change in Viral Load from Baseline | -2.85 log10 IU/mL | Standard Deviation 0.421 |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy | Day 3 Mean change in Viral Load from Baseline | -3.10 log10 IU/mL | Standard Deviation 0.257 |
Secondary
Percentage of Participants With End-of-Treatment Response
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation \[\< LLOQ\]) at the end of combination therapy (12 weeks).
Time frame: 12 weeks
Population: All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With End-of-Treatment Response | 83.3 percentage of participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With End-of-Treatment Response | 83.3 percentage of participants |
Secondary
Percentage of Participants With Extended Rapid Virologic Response
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation \[\< LLOQ\]) at Weeks 4 through 12 of combination therapy.
Time frame: Weeks 4 to 12
Population: All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With Extended Rapid Virologic Response | 83.3 percentage of participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With Extended Rapid Virologic Response | 83.3 percentage of participants |
Secondary
Percentage of Participants With Rapid Virologic Response
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation \[\< LLOQ\]) after 4 weeks of combination therapy.
Time frame: 4 weeks
Population: All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With Rapid Virologic Response | 83.3 percentage of participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With Rapid Virologic Response | 100 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 and 24 weeks after the last dose of combination study drug. The LLOQ for the assay was 25 IU/mL.
Time frame: 12 and 24 weeks after last dose of combination study drug
Population: All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy | 12 Weeks Post-treatment | 83.3 percentage of participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy | 24 Weeks Post-treatment | 83.3 percentage of participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy | 12 Weeks Post-treatment | 83.3 percentage of participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy | 24 Weeks Post-treatment | 83.3 percentage of participants |
Other Pre-specified
Resistance-Associated Variants and Phenotypic Resistance
Baseline (pre-dose on Day 1) samples were analyzed for resistance-associated amino acid (AA) variants using population sequencing. Phenotypic resistance to ABT-267 at Baseline was assessed by calculating the fold difference in the the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Day 3 samples were analyzed using population sequencing and were compared with the baseline and appropriate prototypic reference sequences to assess AA changes. Phenotypic resistance at Day 3 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 AA positions and phenotypic resistance at Baseline and Day 3 are presented.
Time frame: Day 1 Pre-dose (Baseline) and Day 3 Pre-dose
Population: All participants who received at least one dose of study drug (ITT population) and had evaluable data were analyzed for baseline resistance-associated amino acid variants; the development of viral resistance was analyzed in all participants who received at least 1 dose of ABT-267 whose samples had sufficient viral titer to allow analysis.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Resistance-Associated Variants and Phenotypic Resistance | Baseline Variants in NS5A (n=5, 6) | 2 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Resistance-Associated Variants and Phenotypic Resistance | Baseline Resistance >10-fold (n=5, 6) | 1 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Resistance-Associated Variants and Phenotypic Resistance | Day 3 Variants in NS5A (n=5, 2) | 6 participants |
| ABT-267 1.5 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Resistance-Associated Variants and Phenotypic Resistance | Day 3 Resistance >10-fold (n=5, 2) | 1 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Resistance-Associated Variants and Phenotypic Resistance | Day 3 Resistance >10-fold (n=5, 2) | 2 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Resistance-Associated Variants and Phenotypic Resistance | Baseline Variants in NS5A (n=5, 6) | 0 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Resistance-Associated Variants and Phenotypic Resistance | Day 3 Variants in NS5A (n=5, 2) | 2 participants |
| ABT-267 25 mg, Then ABT-267, ABT-450/r, ABT-333, Plus RBV | Resistance-Associated Variants and Phenotypic Resistance | Baseline Resistance >10-fold (n=5, 6) | 0 participants |