Hepatitis C, Chronic
Conditions
Keywords
Hepatitis C Virus, Ribavirin-Free, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Chronic Hepatitis C, Compensated cirrhosis, Hepatitis C Genotype 4, Paritaprevir, Ombitasvir, Ritonavir, Ribavirin
Brief summary
The purpose of this study is to evaluate the safety and efficacy of co-administration of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adults with chronic hepatitis C virus infection.
Detailed description
This was a Phase 2, randomized, open-label, combination treatment study of the 2-DAA regimen (ABT-450 150 mg QD + ritonavir 100 mg QD + ABT-267 25 mg QD) in adult HCV GT1b-infected treatment-naïve and Pegylated-interferon/ribavirin (pegIFN/RBV) treatment-experienced participants without cirrhosis and with compensated cirrhosis, and in adult GT4-infected treatment-naïve and pegIFN/RBV treatment-experienced participants without cirrhosis. Treatment Group 5 was not open to enrollment, based on a protocol-specified interim review of results from the treatment-naïve GT4 Groups 1 and 4 that indicated higher sustained virologic response (SVR) rates among participants receiving the 2-DAA regimen with RBV. All other groups completed the study.
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
* Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile * Subjects must meet one of the following: * Treatment-naive: Subject has never received antiviral treatment for hepatitis C infection OR * Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegIFN/RBV); * Body mass index (BMI) is ≥ 18 to \< 38 kg/m\^2. * Chronic HCV genotype 1b infection/with or without cirrhosis or HCV genotype 4 infection/without cirrhosis for at least 6 months prior to study screening. * 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 were pregnant or planned to become pregnant, or breastfeeding, or GT4-infected males whose partners were pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug/RBV. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment | 12 weeks after the last actual dose of 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 weeks after the last dose of study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment | 24 weeks after the last actual dose of 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 \[\<LLOQ\]) 24 weeks after the last dose of study drug. |
| Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. | Baseline (Day 1), Day 3, and Treatment Weeks 1, 2 ,3 ,4, 6, 8, 10, and 12 for all participants and Treatment Weeks 16, 20 and 24 for Groups 7 and 8 | Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation \[≥ LLOQ\] after HCV RNA \< LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA \[2 consecutive HCV RNA measurements \> 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline\] at any time point during treatment), or fail to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks \[≥ 36 days\] of treatment). |
| Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. | Within 12 weeks after the last dose of study drug | Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA \< LLOQ at the end of treatment. |
| Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events | From the start of study drug administration until 30 days after the last dose,16 weeks for Groups 1, 2, 3, 4, and 6, and 28 weeks for Groups 7 and 8. | Treatment-emergent adverse events were defined as any event that began or worsened in severity after initiation of study drug through 30 days after the last dose of study drug. |
Participant flow
Pre-assignment details
The study originally planned to enroll Group 5 (GT4 treatment-experienced, 2-DAA regimen for 12 weeks), but based on a protocol-specified interim review of results from the treatment-naïve GT4 Groups 1 and 4 that indicated higher SVR rates among participants receiving the 2-DAA regimen with RBV, Group 5 was not opened to enrollment.
Participants by arm
| Arm | Count |
|---|---|
| Group 1 ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants | 44 |
| Group 2 ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants | 42 |
| Group 3 ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants | 40 |
| Group 4 ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if \< 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants | 42 |
| Group 6 ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if \< 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants | 49 |
| Group 7 ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis | 47 |
| Group 8 ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis | 52 |
| Total | 316 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
| Overall Study | Adverse event and withdrew consent | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lost to Follow-up | 3 | 3 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Patient's decision | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Group 1 | Group 2 | Group 3 | Group 4 | Group 6 | Group 7 | Group 8 | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 48.9 years STANDARD_DEVIATION 10 | 55.8 years STANDARD_DEVIATION 6.9 | 54.2 years STANDARD_DEVIATION 9.6 | 44.2 years STANDARD_DEVIATION 12.7 | 50.9 years STANDARD_DEVIATION 10.1 | 57.8 years STANDARD_DEVIATION 7.1 | 57.1 years STANDARD_DEVIATION 6 | 52.8 years STANDARD_DEVIATION 10.1 |
| Sex: Female, Male Female | 20 Participants | 17 Participants | 25 Participants | 14 Participants | 13 Participants | 24 Participants | 19 Participants | 132 Participants |
| Sex: Female, Male Male | 24 Participants | 25 Participants | 15 Participants | 28 Participants | 36 Participants | 23 Participants | 33 Participants | 184 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 |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 30 / 44 | 24 / 42 | 26 / 40 | 32 / 42 | 38 / 49 | 34 / 47 | 33 / 52 |
| serious Total, serious adverse events | 2 / 44 | 1 / 42 | 1 / 40 | 0 / 42 | 0 / 49 | 3 / 47 | 2 / 52 |
Outcome results
Primary
Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment
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 weeks after the last dose of study drug.
Time frame: 12 weeks after the last actual dose of study drug
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment | 90.9 Percentage of participants |
| Group 2 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment | 95.2 Percentage of participants |
| Group 3 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment | 90.0 Percentage of participants |
| Group 4 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment | 100 Percentage of participants |
| Group 6 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment | 100 Percentage of participants |
| Group 7 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment | 97.9 Percentage of participants |
| Group 8 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment | 98.1 Percentage of participants |
p-value: 0.381Regression, Logistic
p-value: 0.086Stratum-adjusted Mantel-Haenszel
Secondary
Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure.
Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation \[≥ LLOQ\] after HCV RNA \< LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA \[2 consecutive HCV RNA measurements \> 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline\] at any time point during treatment), or fail to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks \[≥ 36 days\] of treatment).
Time frame: Baseline (Day 1), Day 3, and Treatment Weeks 1, 2 ,3 ,4, 6, 8, 10, and 12 for all participants and Treatment Weeks 16, 20 and 24 for Groups 7 and 8
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. | 2.3 Percentage of participants |
| Group 2 | Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. | 0 Percentage of participants |
| Group 3 | Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. | 2.5 Percentage of participants |
| Group 4 | Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. | 0 Percentage of participants |
| Group 6 | Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. | 0 Percentage of participants |
| Group 7 | Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. | 0 Percentage of participants |
| Group 8 | Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. | 0 Percentage of participants |
Secondary
Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse.
Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA \< LLOQ at the end of treatment.
Time frame: Within 12 weeks after the last dose of study drug
Population: All randomized participants who received at least 1 dose of study drug and completed treatment with HCV RNA \< LLOQ at the final treatment visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. | 4.8 Percentage of participants |
| Group 2 | Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. | 0 Percentage of participants |
| Group 3 | Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. | 7.7 Percentage of participants |
| Group 4 | Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. | 0 Percentage of participants |
| Group 6 | Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. | 0 Percentage of participants |
| Group 7 | Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. | 0 Percentage of participants |
| Group 8 | Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. | 1.9 Percentage of participants |
Secondary
Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\<LLOQ\]) 24 weeks after the last dose of study drug.
Time frame: 24 weeks after the last actual dose of study drug
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment | 86.4 Percentage of participants |
| Group 2 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment | 92.9 Percentage of participants |
| Group 3 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment | 90.0 Percentage of participants |
| Group 4 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment | 100.0 Percentage of participants |
| Group 6 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment | 100.0 Percentage of participants |
| Group 7 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment | 97.9 Percentage of participants |
| Group 8 | Percentage of Participants in Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment | 98.1 Percentage of participants |
Secondary
Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events
Treatment-emergent adverse events were defined as any event that began or worsened in severity after initiation of study drug through 30 days after the last dose of study drug.
Time frame: From the start of study drug administration until 30 days after the last dose,16 weeks for Groups 1, 2, 3, 4, and 6, and 28 weeks for Groups 7 and 8.
Population: All randomized participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Group 1 | Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events | 77.3 Percentage of participants |
| Group 2 | Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events | 73.8 Percentage of participants |
| Group 3 | Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events | 80.0 Percentage of participants |
| Group 4 | Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events | 88.1 Percentage of participants |
| Group 6 | Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events | 85.7 Percentage of participants |
| Group 7 | Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events | 85.1 Percentage of participants |
| Group 8 | Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events | 71.2 Percentage of participants |