Chronic Hepatitis C, Hepatitis C (HCV), Hepatitis C Genotype 1
Conditions
Keywords
Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, HCV, Chronic Hepatitis C
Brief summary
This is a study of combination direct-acting antiviral agents (DAA) with or without ribavirin (RBV) in patients with chronic Hepatitis C Virus (HCV).
Detailed description
A study to evaluate the safety and effectiveness of experimental drugs ABT-450, ABT-267 (also known as ombitasvir), ABT-333 (also known as dasabuvir), ritonavir, and ribavirin in participants with HCV. The study will test the safety and effects of combinations of these drugs in treatments up to 24 weeks.
Interventions
Sponsors
AbbVie (prior sponsor, Abbott)
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
* Males and females 18-70 years old, inclusive * Females must be post-menopausal for more than 2 years or surgically sterile or practicing specific forms of birth control * Chronic hepatitis C virus (HCV), genotype 1 infection * Treatment-naive OR null-responders to previous treatment with pegylated interferon (pegIFN) and ribavirin (at least 12 weeks of treatment and failure to achieve a 2 log10 HCV RNA decrease at Week 12) * No evidence of liver cirrhosis
Exclusion criteria
* Significant liver disease with any cause other than HCV as the primary cause * Positive hepatitis B surface antigen and anti-human immunodeficiency virus antibody * Positive screen for drugs and alcohol * Significant sensitivity to any drug * Use of contraindicated or prohibited medications within 1 month of dosing * Abnormal laboratory tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | From the time of study drug administration until 30 days following discontinuation of study drug administration (up to 28 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 to ribavirin, 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 or prolonged hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention. |
| Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | Post Treatment Week 24 | The percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (SVR24), defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than the lower limit of quantitation (LLOQ), without any confirmed quantifiable (≥ LLOQ) post-treatment value before that time point. HCV RNA levels were measured from plasma by a central laboratory. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoint was the comparison between treatment-naïve participants following 8 weeks of treatment with 3 DAAs and ribavirin and those with 12 weeks of treatment with 3 DAAs and ribavirin (Group A versus Group G). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment of Different Durations With 3 Direct-acting Antiviral Agents (DAAs) and Ribavirin | Post-Treatment Week 24 | This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (HCV RNA \< LLOQ at post-treatment Week 24) following treatment with 3 DAAs (ABT-450/ritonavir, ABT-267, and ABT-333) and ribavirin in both treatment naïve and null-responder participants for 8 weeks (Group A) versus 12 weeks (Groups F + G + K + L) versus 24 weeks (Groups H + I + M + N). |
| Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 2 DAAs and Ribavirin Versus 3 DAAs and Ribavirin | Post-Treatment Week 24 | This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA \< LLOQ at post-treatment Week 24) following treatment with 2 DAAs (ABT-450/ritonavir plus ABT-333 \[Group B\] or ABT-450/ritonavir plus ABT-267 \[Groups C + D + J\]) and ribavirin versus 3 DAAs (ABT-450/ritonavir plus ABT-333 and ABT-267) and ribavirin (Groups F + G + K + L). |
| Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 3 DAAs With Versus Without Ribavirin | Post-Treatment Week 24 | This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA \< LLOQ at post-treatment Week 24) following treatment with 3 DAAs with or without ribavirin (Group E versus Groups F + G + K + L). |
| Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders | Post-Treatment Week 24 | This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA \< LLOQ at post-treatment Week 24) following treatment with 3 DAAs and ribavirin in participants who were treatment-naïve versus those who were null-responders to previous HCV therapy (Groups F + G + H + I versus Groups K + L + M + N). |
Countries
Australia, Canada, France, Germany, New Zealand, Puerto Rico, Spain, United Kingdom, United States
Participant flow
Recruitment details
This was a Phase 2, open-label, randomized, combination treatment study of multiple doses of ABT-450/ritonavir, and ABT-267 and/or ABT-333 with or without ribavirin in hepatitis C virus (HCV) genotype 1-infected treatment-naïve patients and previous null responders to pegylated interferon (pegIFN) and ribavirin treatment.
Participants by arm
| Arm | Count |
|---|---|
| Group A Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 8 weeks. | 80 |
| Group B Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks. | 41 |
| Group C Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks. | 39 |
| Group D Treatment-naïve participants received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks. | 40 |
| Group E Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ABT-333 400 mg twice daily for 12 weeks. | 79 |
| Group F Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks. | 39 |
| Group G Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks. | 40 |
| Group H Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks. | 40 |
| Group I Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks. | 40 |
| Group J Participants who were null-responders to previous HCV treatment received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks. | 45 |
| Group K Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks. | 23 |
| Group L Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks. | 22 |
| Group M Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks. | 23 |
| Group N Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks. | 20 |
| Total | 571 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 | FG012 | FG013 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 2 | 0 | 2 | 3 | 1 | 2 | 2 | 0 | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Not Treated | 0 | 2 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 2 | 0 | 1 | 0 | 2 |
| Overall Study | Other | 2 | 3 | 0 | 2 | 3 | 0 | 1 | 0 | 3 | 1 | 2 | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Group A | Group B | Group C | Group D | Group E | Group F | Group G | Group H | Group I | Group J | Group K | Group L | Group M | Group N | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 50.1 years STANDARD_DEVIATION 9.99 | 50.8 years STANDARD_DEVIATION 9.84 | 51.1 years STANDARD_DEVIATION 8.07 | 49.0 years STANDARD_DEVIATION 10.59 | 48.3 years STANDARD_DEVIATION 10.53 | 49.4 years STANDARD_DEVIATION 9.72 | 51.0 years STANDARD_DEVIATION 11.08 | 51.5 years STANDARD_DEVIATION 11.95 | 51.5 years STANDARD_DEVIATION 9.78 | 50.6 years STANDARD_DEVIATION 11.19 | 48.5 years STANDARD_DEVIATION 12.91 | 51.2 years STANDARD_DEVIATION 12.07 | 51.5 years STANDARD_DEVIATION 9.06 | 54.6 years STANDARD_DEVIATION 11.78 | 50.3 years STANDARD_DEVIATION 10.49 |
| Sex: Female, Male Female | 34 Participants | 23 Participants | 14 Participants | 20 Participants | 34 Participants | 19 Participants | 16 Participants | 22 Participants | 24 Participants | 18 Participants | 7 Participants | 10 Participants | 8 Participants | 8 Participants | 257 Participants |
| Sex: Female, Male Male | 46 Participants | 18 Participants | 25 Participants | 20 Participants | 45 Participants | 20 Participants | 24 Participants | 18 Participants | 16 Participants | 27 Participants | 16 Participants | 12 Participants | 15 Participants | 12 Participants | 314 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 |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 64 / 80 | 33 / 41 | 66 / 79 | 59 / 79 | 66 / 79 | 74 / 80 | 40 / 45 | 36 / 45 | 34 / 43 |
| serious Total, serious adverse events | 0 / 80 | 0 / 41 | 2 / 79 | 2 / 79 | 1 / 79 | 1 / 80 | 0 / 45 | 0 / 45 | 2 / 43 |
Outcome results
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 to ribavirin, 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 or prolonged 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: From the time of study drug administration until 30 days following discontinuation of study drug administration (up to 28 weeks).
Population: Safety population. Treatment groups differing only in ABT-450 dose (100 mg, 150 mg or 200 mg) were combined for safety analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Group A | Number of Participants With Adverse Events (AEs) | Any severe adverse event | 3 participants |
| Group A | Number of Participants With Adverse Events (AEs) | Any adverse event at least possibly DAA-related | 58 participants |
| Group A | Number of Participants With Adverse Events (AEs) | Any adverse event | 67 participants |
| Group A | Number of Participants With Adverse Events (AEs) | Any serious adverse event | 0 participants |
| Group A | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 1 participants |
| Group A | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 0 participants |
| Group A | Number of Participants With Adverse Events (AEs) | Any AE leading to ribavirin dose modification | 2 participants |
| Group A | Number of Participants With Adverse Events (AEs) | Any fatal adverse events | 0 participants |
| Group B | Number of Participants With Adverse Events (AEs) | Any serious adverse event | 0 participants |
| Group B | Number of Participants With Adverse Events (AEs) | Any adverse event at least possibly DAA-related | 29 participants |
| Group B | Number of Participants With Adverse Events (AEs) | Any AE leading to ribavirin dose modification | 2 participants |
| Group B | Number of Participants With Adverse Events (AEs) | Any severe adverse event | 0 participants |
| Group B | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 1 participants |
| Group B | Number of Participants With Adverse Events (AEs) | Any adverse event | 36 participants |
| Group B | Number of Participants With Adverse Events (AEs) | Any fatal adverse events | 0 participants |
| Group B | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 0 participants |
| Group C + D | Number of Participants With Adverse Events (AEs) | Any fatal adverse events | 0 participants |
| Group C + D | Number of Participants With Adverse Events (AEs) | Any serious adverse event | 2 participants |
| Group C + D | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 2 participants |
| Group C + D | Number of Participants With Adverse Events (AEs) | Any adverse event at least possibly DAA-related | 53 participants |
| Group C + D | Number of Participants With Adverse Events (AEs) | Any AE leading to ribavirin dose modification | 4 participants |
| Group C + D | Number of Participants With Adverse Events (AEs) | Any severe adverse event | 3 participants |
| Group C + D | Number of Participants With Adverse Events (AEs) | Any adverse event | 71 participants |
| Group C + D | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 0 participants |
| Group E | Number of Participants With Adverse Events (AEs) | Any adverse event at least possibly DAA-related | 51 participants |
| Group E | Number of Participants With Adverse Events (AEs) | Any AE leading to ribavirin dose modification | 0 participants |
| Group E | Number of Participants With Adverse Events (AEs) | Any fatal adverse events | 0 participants |
| Group E | Number of Participants With Adverse Events (AEs) | Any severe adverse event | 5 participants |
| Group E | Number of Participants With Adverse Events (AEs) | Any serious adverse event | 2 participants |
| Group E | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 0 participants |
| Group E | Number of Participants With Adverse Events (AEs) | Any adverse event | 68 participants |
| Group E | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 1 participants |
| Group F + G | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 3 participants |
| Group F + G | Number of Participants With Adverse Events (AEs) | Any serious adverse event | 1 participants |
| Group F + G | Number of Participants With Adverse Events (AEs) | Any fatal adverse events | 0 participants |
| Group F + G | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 0 participants |
| Group F + G | Number of Participants With Adverse Events (AEs) | Any adverse event at least possibly DAA-related | 57 participants |
| Group F + G | Number of Participants With Adverse Events (AEs) | Any AE leading to ribavirin dose modification | 9 participants |
| Group F + G | Number of Participants With Adverse Events (AEs) | Any severe adverse event | 3 participants |
| Group F + G | Number of Participants With Adverse Events (AEs) | Any adverse event | 71 participants |
| Group H + I | Number of Participants With Adverse Events (AEs) | Any adverse event at least possibly DAA-related | 68 participants |
| Group H + I | Number of Participants With Adverse Events (AEs) | Any fatal adverse events | 0 participants |
| Group H + I | Number of Participants With Adverse Events (AEs) | Any severe adverse event | 3 participants |
| Group H + I | Number of Participants With Adverse Events (AEs) | Any AE leading to ribavirin dose modification | 10 participants |
| Group H + I | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 3 participants |
| Group H + I | Number of Participants With Adverse Events (AEs) | Any serious adverse event | 1 participants |
| Group H + I | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 1 participants |
| Group H + I | Number of Participants With Adverse Events (AEs) | Any adverse event | 77 participants |
| Group J | Number of Participants With Adverse Events (AEs) | Any fatal adverse events | 0 participants |
| Group J | Number of Participants With Adverse Events (AEs) | Any adverse event | 42 participants |
| Group J | Number of Participants With Adverse Events (AEs) | Any severe adverse event | 1 participants |
| Group J | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 0 participants |
| Group J | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 1 participants |
| Group J | Number of Participants With Adverse Events (AEs) | Any serious adverse event | 0 participants |
| Group J | Number of Participants With Adverse Events (AEs) | Any adverse event at least possibly DAA-related | 35 participants |
| Group J | Number of Participants With Adverse Events (AEs) | Any AE leading to ribavirin dose modification | 3 participants |
| Group K + L | Number of Participants With Adverse Events (AEs) | Any adverse event | 39 participants |
| Group K + L | Number of Participants With Adverse Events (AEs) | Any adverse event at least possibly DAA-related | 30 participants |
| Group K + L | Number of Participants With Adverse Events (AEs) | Any severe adverse event | 1 participants |
| Group K + L | Number of Participants With Adverse Events (AEs) | Any serious adverse event | 0 participants |
| Group K + L | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 0 participants |
| Group K + L | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 0 participants |
| Group K + L | Number of Participants With Adverse Events (AEs) | Any fatal adverse events | 0 participants |
| Group K + L | Number of Participants With Adverse Events (AEs) | Any AE leading to ribavirin dose modification | 1 participants |
| Group M + N | Number of Participants With Adverse Events (AEs) | Any fatal adverse events | 0 participants |
| Group M + N | Number of Participants With Adverse Events (AEs) | Any AE leading to ribavirin dose modification | 3 participants |
| Group M + N | Number of Participants With Adverse Events (AEs) | Any AE leading to interruption of study drug | 0 participants |
| Group M + N | Number of Participants With Adverse Events (AEs) | Any AE leading to discontinuation of study drug | 1 participants |
| Group M + N | Number of Participants With Adverse Events (AEs) | Any serious adverse event | 2 participants |
| Group M + N | Number of Participants With Adverse Events (AEs) | Any severe adverse event | 1 participants |
| Group M + N | Number of Participants With Adverse Events (AEs) | Any adverse event at least possibly DAA-related | 28 participants |
| Group M + N | Number of Participants With Adverse Events (AEs) | Any adverse event | 37 participants |
Primary
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin
The percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (SVR24), defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than the lower limit of quantitation (LLOQ), without any confirmed quantifiable (≥ LLOQ) post-treatment value before that time point. HCV RNA levels were measured from plasma by a central laboratory. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoint was the comparison between treatment-naïve participants following 8 weeks of treatment with 3 DAAs and ribavirin and those with 12 weeks of treatment with 3 DAAs and ribavirin (Group A versus Group G).
Time frame: Post Treatment Week 24
Population: Intent-to-treat population (all participants who received at least 1 dose of direct-acting antiviral agent); participants with missing data were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 87.5 percentage of participants |
| Group B | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 82.9 percentage of participants |
| Group C + D | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 84.6 percentage of participants |
| Group E | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 92.5 percentage of participants |
| Group F + G | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 88.6 percentage of participants |
| Group H + I | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 97.4 percentage of participants |
| Group J | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 95.0 percentage of participants |
| Group K + L | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 92.5 percentage of participants |
| Group M + N | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 90.0 percentage of participants |
| Group J | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 88.9 percentage of participants |
| Group K | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 91.3 percentage of participants |
| Group L | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 95.5 percentage of participants |
| Group M | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 91.3 percentage of participants |
| Group N | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose for 8 Weeks Versus 12 Weeks of Treatment With 3 DAAs and Ribavirin | 100.0 percentage of participants |
Comparison: The primary efficacy endpoint was the comparison of the percentage of treatment-naïve participants with SVR24 after treatment with 3 DAAs (at the 150 mg ABT-450 dose) and ribavirin for 8 weeks (Group A) versus 12 weeks (Group G).~Logistic regression with baseline log10 HCV RNA level, treatment group, Interleukin 28B genotype (CC or non-CC), HCV subgenotype (1a or non-1a), and geographic region (US or non-US) as predictors.p-value: 0.40695% CI: [0.09, 2.61]Regression, Logistic
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 2 DAAs and Ribavirin Versus 3 DAAs and Ribavirin
This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA \< LLOQ at post-treatment Week 24) following treatment with 2 DAAs (ABT-450/ritonavir plus ABT-333 \[Group B\] or ABT-450/ritonavir plus ABT-267 \[Groups C + D + J\]) and ribavirin versus 3 DAAs (ABT-450/ritonavir plus ABT-333 and ABT-267) and ribavirin (Groups F + G + K + L).
Time frame: Post-Treatment Week 24
Population: Intent-to-treat population; participants with missing data were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 2 DAAs and Ribavirin Versus 3 DAAs and Ribavirin | 82.9 percentage of participants |
| Group B | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 2 DAAs and Ribavirin Versus 3 DAAs and Ribavirin | 88.7 percentage of participants |
| Group C + D | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 2 DAAs and Ribavirin Versus 3 DAAs and Ribavirin | 95.2 percentage of participants |
Comparison: The percentage of participants with SVR24 after treatment with 2 DAAs and ribavirin versus 3 DAAs and ribavirin was compared using stratum-adjusted Mantel-Haenszel (MH) method with Interleukin 28B genotype (CC or non-CC) and HCV subgenotype (1a or non-1a).p-value: 0.06895% CI: [-25.2, 0.88]Mantel Haenszel
Comparison: The percentage of participants with SVR24 after treatment with 2 DAAs and ribavirin versus 3 DAAs and ribavirin was compared using stratum-adjusted Mantel-Haenszel (MH) method with Interleukin 28B genotype (CC or non-CC) and HCV subgenotype (1a or non-1a).p-value: 0.06595% CI: [-13.93, 0.43]Mantel Haenszel
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 3 DAAs With Versus Without Ribavirin
This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA \< LLOQ at post-treatment Week 24) following treatment with 3 DAAs with or without ribavirin (Group E versus Groups F + G + K + L).
Time frame: Post-Treatment Week 24
Population: Intent-to-treat population; participants with missing data were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 3 DAAs With Versus Without Ribavirin | 88.6 percentage of participants |
| Group B | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment for 12 Weeks With 3 DAAs With Versus Without Ribavirin | 95.2 percentage of participants |
Comparison: The percentage of participants with SVR24 after treatment with 3 DAAs with and without ribavirin was compared using a stratum-adjusted Mantel-Haenszel (MH) method with Interleukin 28B genotype (CC or non-CC) and HCV subgenotype (1a or non-1a).p-value: 0.10695% CI: [-15.77, 1.51]Mantel Haenszel
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment of Different Durations With 3 Direct-acting Antiviral Agents (DAAs) and Ribavirin
This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (HCV RNA \< LLOQ at post-treatment Week 24) following treatment with 3 DAAs (ABT-450/ritonavir, ABT-267, and ABT-333) and ribavirin in both treatment naïve and null-responder participants for 8 weeks (Group A) versus 12 weeks (Groups F + G + K + L) versus 24 weeks (Groups H + I + M + N).
Time frame: Post-Treatment Week 24
Population: Intent-to-treat population; participants with missing data were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment of Different Durations With 3 Direct-acting Antiviral Agents (DAAs) and Ribavirin | 87.5 percentage of participants |
| Group B | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment of Different Durations With 3 Direct-acting Antiviral Agents (DAAs) and Ribavirin | 95.2 percentage of participants |
| Group C + D | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose Following Treatment of Different Durations With 3 Direct-acting Antiviral Agents (DAAs) and Ribavirin | 92.7 percentage of participants |
Comparison: The percentage of participants with SVR24 after treatment for 8 weeks versus 12 weeks was compared using logistic regression with treatment group, baseline log10 HCV RNA level, HCV subgenotype (1a or non-1a), geographic region (US or non-US), Interleukin 28B genotype (CC or non-CC), and ABT-450/ritonavir dose and population (treatment-naïve or null-responders) as predictors.p-value: 0.26695% CI: [0.08, 2.02]Regression, Logistic
Comparison: The percentage of participants with SVR24 after treatment for 8 weeks versus 24 weeks was compared using logistic regression with treatment group, baseline log10 HCV RNA level, HCV subgenotype (1a or non-1a), geographic region (US or non-US), Interleukin 28B genotype (CC or non-CC), ABT-450/ritonavir dose and population (treatment-naïve or null-responders) as predictors.p-value: 0.52595% CI: [0.18, 2.4]Regression, Logistic
Comparison: The percentage of participants with SVR24 after treatment for 12 weeks versus 24 weeks was compared using logistic regression with treatment group, baseline log10 HCV RNA level, HCV subgenotype (1a or non-1a), geographic region (US or non-US), Interleukin 28B genotype (CC or non-CC), ABT-450/ritonavir dose and population (treatment-naïve or null-responders) as predictors.p-value: 0.37595% CI: [0.55, 4.92]Regression, Logistic
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders
This outcome measure compares the percentage of participants achieving sustained virologic response 24 weeks post-dose (HCV RNA \< LLOQ at post-treatment Week 24) following treatment with 3 DAAs and ribavirin in participants who were treatment-naïve versus those who were null-responders to previous HCV therapy (Groups F + G + H + I versus Groups K + L + M + N).
Time frame: Post-Treatment Week 24
Population: Intent-to-treat population; participants with missing data were counted as non-responders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group A | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders | 93.7 percentage of participants |
| Group B | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-dose in Treatment-naïve Versus Null-responders | 94.3 percentage of participants |
Comparison: The percentage of participants with SVR24 after treatment with 3 DAAs and ribavirin in treatment-naïve versus null-responders was compared using logistic regression with treatment group, baseline log10 HCV RNA level, HCV subgenotype (1a or non-1a), geographic region (US or non-US), Interleukin 28B genotype (CC or non-CC), and ABT-450/ritonavir dose as predictors.p-value: 0.61695% CI: [0.37, 5.34]Regression, Logistic