Chronic Hepatitis C Infection
Conditions
Keywords
Hepatitis C Genotype 4, Chronic Hepatitis, Interferon-Free, Hepatitis C Virus (HCV), Renal Transplant, Liver Transplant, Hepatitis C Genotype 1
Brief summary
The purpose of this study is to evaluate the safety and efficacy of ABT-450/r/ABT-267 with or without ABT-333 and with or without ribavirin (RBV) in adult liver or renal transplant recipients with hepatitis C virus (HCV) genotype 1 or 4 (GT1 or GT4) infection.
Interventions
Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet
Tablet; ombitasvir coformulated with paritaprevir and ritonavir
DRUGribavirin
tablet
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, at least 18 years of age at the time of screening. * Currently taking an immunosuppressant regimen based on either tacrolimus or cyclosporine. Corticosteroids such as prednisone or prednisolone are permitted as components of the immunosuppressant regimen providing the dose is not more than 10 mg/day. * Hepatitis C virus (HCV) interferon (IFN) therapy treatment-naïve or -experienced, either pre- or post-liver or renal transplant. * Screening HCV genotype testing indicating infection with genotype 1 or 4 (GT1 or GT4) only.
Exclusion criteria
* Use of everolimus or sirolimus as part of the immunosuppressive regimen within 2 months of Screening Visit. * Use of any medications contraindicated for use with the study regimen as well as those that are contraindicated for use with either ritonavir or ribavirin within 2 weeks prior to study drugs administration or 10 half-lives (if known), whichever is longer. * Positive test result for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab). * Documented history of post-transplant complications directly involving the hepatic or renal vasculature as appropriate to the organ transplanted, e.g., thrombosis of the portal vein, the hepatic artery and/or hepatic vein. * Clinically significant abnormalities, other than HCV infection, in a subject post-transplant based upon the medical history, physical examination, vital signs, laboratory profile and a 12-lead electrocardiogram (ECG) that make the subject an unsuitable candidate for this study in the opinion of the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 12 weeks after the last actual dose of study drug | SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug. Participants with missing data after backward imputation were imputed as nonresponders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 24 weeks after the last actual dose of study drug | SVR24 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 24 weeks after the last dose of study drug. Participants with missing data after backward imputation were imputed as nonresponders. |
| Percentage of Participants With On-treatment Virologic Failure | Up to 12 weeks (for 12-week treatment) or 24 weeks (for 24-week treatment) | On-treatment virologic failure was defined as confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment, or confirmed HCV RNA ≥ LLOQ at any point during treatment after HCV RNA \< LLOQ, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks (≥ 36 days) of treatment. |
| Percentage of Participants With Post-treatment Relapse | From the end of treatment through 12 weeks after the last dose of study drug | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels \< LLOQ at the end of treatment. |
Participant flow
Pre-assignment details
This study included a 35-day screening period.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Liver transplant recipients with HCV genotype 1 infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 24 weeks. | 34 |
| Arm B Liver transplant recipients with HCV genotype 1a or genotype 1b (dependent on prior treatment experience and response) infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 24 weeks. | 27 |
| Arm C Liver transplant receipts with HCV genotype 1b infection who were treatment naïve or prior responders to interferon treatment without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) for 24 weeks. | 13 |
| Arm D Liver transplant recipients with HCV genotype 1a infection with Child Pugh A cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (dosed 1,000 or 1,200 mg daily divided twice a day) for 24 weeks. | 4 |
| Arm E Liver transplant recipients with HCV genotype 1b infection with Child Pugh A cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks. | 2 |
| Arm F Liver transplant recipients with HCV genotype 1a infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks. | 22 |
| Arm G Liver transplant recipients with HCV genotype 1b infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) for 12 weeks. | 12 |
| Arm H Renal transplant recipients with HCV genotype 1a infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks. | 9 |
| Arm I Renal transplant recipients with HCV genotype 1b infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) with dasabuvir (250 mg twice daily) for 12 weeks. | 3 |
| Arm J Liver transplant recipients with HCV genotype 4 infection without cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 12 weeks. | 2 |
| Arm K Liver transplant recipients with HCV genotype 4 infection with Child Pugh A cirrhosis received ombitasvir/paritaprevir/ritonavir (25 mg/150 mg/100 mg once daily) plus weight-based ribavirin (1,000 or 1,200 mg daily divided twice a day) for 24 weeks. | 1 |
| Total | 129 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 |
| Overall Study | Withdrew Consent | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Arm C | Arm D | Arm E | Arm F | Arm G | Arm H | Arm I | Arm J | Arm K | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.6 years STANDARD_DEVIATION 6.62 | 58.0 years STANDARD_DEVIATION 6.66 | 61.8 years STANDARD_DEVIATION 5.76 | 59.8 years STANDARD_DEVIATION 10.78 | 78.0 years STANDARD_DEVIATION 1.41 | 58.3 years STANDARD_DEVIATION 9.35 | 62.2 years STANDARD_DEVIATION 7.64 | 58.0 years STANDARD_DEVIATION 8 | 57.3 years STANDARD_DEVIATION 9.29 | 63.5 years STANDARD_DEVIATION 7.78 | 50.0 years | 59.6 years STANDARD_DEVIATION 7.73 |
| Sex: Female, Male Female | 7 Participants | 4 Participants | 5 Participants | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 25 Participants |
| Sex: Female, Male Male | 27 Participants | 23 Participants | 8 Participants | 4 Participants | 0 Participants | 20 Participants | 10 Participants | 7 Participants | 2 Participants | 2 Participants | 1 Participants | 104 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 27 | 0 / 13 | 0 / 4 | 0 / 2 | 0 / 22 | 0 / 12 | 1 / 9 | 0 / 3 | 0 / 2 | 0 / 1 |
| other Total, other adverse events | 33 / 34 | 27 / 27 | 12 / 13 | 4 / 4 | 2 / 2 | 22 / 22 | 12 / 12 | 8 / 9 | 3 / 3 | 2 / 2 | 1 / 1 |
| serious Total, serious adverse events | 2 / 34 | 1 / 27 | 0 / 13 | 0 / 4 | 0 / 2 | 2 / 22 | 1 / 12 | 4 / 9 | 0 / 3 | 0 / 2 | 0 / 1 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 12 weeks after the last dose of study drug. Participants with missing data after backward imputation were imputed as nonresponders.
Time frame: 12 weeks after the last actual dose of study drug
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 97.1 percentage of participants |
| Arm B | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 96.3 percentage of participants |
| Arm C | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm D | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm E | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm F | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 95.5 percentage of participants |
| Arm G | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm H | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 66.7 percentage of participants |
| Arm I | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm J | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| Arm K | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment, or confirmed HCV RNA ≥ LLOQ at any point during treatment after HCV RNA \< LLOQ, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks (≥ 36 days) of treatment.
Time frame: Up to 12 weeks (for 12-week treatment) or 24 weeks (for 24-week treatment)
Population: All participants who received at least 1 dose of study drug (ITT population).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Arm B | Percentage of Participants With On-treatment Virologic Failure | 3.7 percentage of participants |
| Arm C | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Arm D | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Arm E | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Arm F | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Arm G | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Arm H | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Arm I | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Arm J | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
| Arm K | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels \< LLOQ at the end of treatment.
Time frame: From the end of treatment through 12 weeks after the last dose of study drug
Population: All participants who received at least 1 dose of study drug, completed treatment, and had HCV RNA \<LLOQ at the final treatment visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants With Post-treatment Relapse | 3.0 percentage of participants |
| Arm B | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm C | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm D | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm E | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm F | Percentage of Participants With Post-treatment Relapse | 4.8 percentage of participants |
| Arm G | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm H | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm I | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm J | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
| Arm K | Percentage of Participants With Post-treatment Relapse | 0 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24)
SVR24 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 24 weeks after the last dose of study drug. Participants with missing data after backward imputation were imputed as nonresponders.
Time frame: 24 weeks after the last actual dose of study drug
Population: All participants who received at least 1 dose of study drug (ITT population).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 97.1 percentage of participants |
| Arm B | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 96.3 percentage of participants |
| Arm C | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 100 percentage of participants |
| Arm D | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 100 percentage of participants |
| Arm E | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 100 percentage of participants |
| Arm F | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 95.5 percentage of participants |
| Arm G | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 100 percentage of participants |
| Arm H | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 66.7 percentage of participants |
| Arm I | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 100 percentage of participants |
| Arm J | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 100 percentage of participants |
| Arm K | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 100 percentage of participants |