Chronic Hepatitis C Infection
Conditions
Keywords
Hepatitis C, Interferon-Free, Treatment Experienced, Chronic Hepatitis C, Hepatitis C Virus
Brief summary
The purpose of this study is to evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir and dasabuvir with or without sofosbuvir (SOF) and ribavirin (RBV) in DAA treatment-experienced adults with Genotype 1 Chronic Hepatitis C Virus infection. This study will contain 2 parts. Part 1: Approximately 20 participants and at least 10 of the 20 participants previously treated with the combination of ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without RBV, and experienced treatment failure. Part 2: Approximately 10 participants and all participants previously treated with SOF/ledipasvir and experienced treatment failure.
Detailed description
Efficacy, safety, and demographic analyses were performed separately for the 2 study parts using the intent-to-treat (ITT) population, which consists of all enrolled participants who received at least one dose of study drug.
Interventions
tablet, ombitasvir coformulated with paritaprevir and ritonavir; tablet, dasabuvir
DRUGSofosbuvir
tablet
DRUGRibavirin
tablet
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* History of previous direct acting antiviral (DAA) therapy failure; Part 2 only: history of previous direct acting antiviral (DAA) therapy failure and received at least 8 weeks of SOF/ledipasvir; participant must be treatment naïve to all other anti-HCV therapies * HCV genotype 1 infection * Females must be post-menopausal, of non-child bearing potential or practicing specific forms of birth control
Exclusion criteria
* Positive screen for hepatitis B surface antigen or anti-human immunodeficiency virus antibody * Discontinuation of the prior DAA treatment for reasons other than virologic failure * Confirmed presence of hepatocellular carcinoma * Abnormal lab tests
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Part 1 Participants With Sustained Virologic Response 12 (SVR12) Weeks Posttreatment | 12 weeks after the last dose of active 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Part 2 Participants With Sustained Virologic Response 12 (SVR12) Weeks Post-treatment | 12 weeks after the last dose of active drug | SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug |
| Percentage of Participants With On-treatment Virologic Failure | Up to week 24 | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after \< LLOQ during treatment, confirmed increase of \> 1 log (subscript)10(subscript) IU/mL above the lowest post-baseline HCV RNA during treatment, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks of treatment. |
| Percentage of Participants With Post-Treatment Relapse | Within 12 weeks after the last actual dose of active study drug | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after the last dose of study drug among participants completing treatment and with HCV RNA \< LLOQ at the end of treatment. |
Participant flow
Recruitment details
Efficacy, safety, and demographic analyses were performed separately for the 2 study parts using the intent-to-treat (ITT) population, which consists of all enrolled participants who received at least one dose of study drug.
Pre-assignment details
The intent-to-treat (ITT) population consisted of all enrolled participants who received at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, 3-DAA With SOF With or Without RBV 3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg once daily \[QD\] and dasabuvir 250 mg twice daily \[BID\]) and sofosbuvir (SOF) 400 mg QD with or without ribavirin (RBV; weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance \< 50 mL/min) for 12 or 24 weeks | 22 |
| Part 2, 3-DAA With RBV 3-DAA (ombitasvir/paritaprevir/ritonavir 25 mg/150 mg/100 mg QD and dasabuvir 250 mg BID) with RBV (weight-based dosing 1000 or 1200 mg divided BID or renally adjusted for participants with creatinine clearance \< 50 mL/min) for 24 weeks | 7 |
| Total | 29 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Re-entered treatment in a previous study | 1 | 0 |
| Overall Study | site closure | 1 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1, 3-DAA With SOF With or Without RBV | Part 2, 3-DAA With RBV | Total |
|---|---|---|---|
| Age, Continuous | 58.0 years STANDARD_DEVIATION 6.41 | 65.3 years STANDARD_DEVIATION 9.6 | NA years |
| Sex: Female, Male Female | 7 Participants | 1 Participants | 8 Participants |
| Sex: Female, Male Male | 15 Participants | 6 Participants | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 20 / 22 | 6 / 7 |
| serious Total, serious adverse events | 2 / 22 | 0 / 7 |
Outcome results
Primary
Percentage of Part 1 Participants With Sustained Virologic Response 12 (SVR12) Weeks Posttreatment
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.
Time frame: 12 weeks after the last dose of active drug
Population: All Part 1 participants who received at least 1 dose of study drug (ITT population). Per protocol, data from Parts 1 and 2 were not combined for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, 3-DAA With SOF With or Without RBV | Percentage of Part 1 Participants With Sustained Virologic Response 12 (SVR12) Weeks Posttreatment | 95.5 percentage of participants |
Secondary
Percentage of Part 2 Participants With Sustained Virologic Response 12 (SVR12) Weeks Post-treatment
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug
Time frame: 12 weeks after the last dose of active drug
Population: All Part 2 participants who received at least 1 dose of study drug (ITT population). Per protocol, data from Parts 1 and 2 were not combined for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, 3-DAA With SOF With or Without RBV | Percentage of Part 2 Participants With Sustained Virologic Response 12 (SVR12) Weeks Post-treatment | 85.7 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after \< LLOQ during treatment, confirmed increase of \> 1 log (subscript)10(subscript) IU/mL above the lowest post-baseline HCV RNA during treatment, or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks of treatment.
Time frame: Up to week 24
Population: All participants who received at least 1 dose of study drug (ITT population). Per protocol, data from Parts 1 and 2 were not combined for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, 3-DAA With SOF With or Without RBV | Percentage of Participants With On-treatment Virologic Failure | 0.0 percentage of participants |
| Part 2, 3-DAA With RBV | Percentage of Participants With On-treatment Virologic Failure | 14.3 percentage of participants |
Secondary
Percentage of Participants With Post-Treatment Relapse
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after the last dose of study drug among participants completing treatment and with HCV RNA \< LLOQ at the end of treatment.
Time frame: Within 12 weeks after the last actual dose of active study drug
Population: All participants who received at least 1 dose of study drug (ITT population) with HCV RNA \< LLOQ at the end of treatment and completed treatment. Per protocol, data from Parts 1 and 2 were not combined for analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part 1, 3-DAA With SOF With or Without RBV | Percentage of Participants With Post-Treatment Relapse | 4.8 percentage of participants |
| Part 2, 3-DAA With RBV | Percentage of Participants With Post-Treatment Relapse | 0.0 percentage of participants |