Chronic Hepatitis C Infection, Compensated Cirrhosis
Conditions
Keywords
Hepatitis C, Chronic Hepatitis C, Compensated Cirrhosis, Cirrhotic, Hepatitis C Genotype 1b, Hepatitis C Virus, Interferon-Free, Child Pugh A, Ribavirin-Free
Brief summary
The purpose of this study was to evaluate the safety and efficacy of ombitasvir/ paritaprevir/ ritonavir and dasabuvir in adults with genotype 1b chronic hepatitis C virus (HCV) infection and cirrhosis.
Detailed description
This was a multicenter study evaluating the efficacy and safety of ombitasvir/ paritaprevir/ritonavir and dasabuvir administered for 12 weeks in HCV genotype 1b (GT1b)-infected, treatment-naïve and previous pegylated interferon (pegIFN)/ ribavirin (RBV) treatment-experienced adults with compensated cirrhosis. The duration of the study was up to 36 weeks (not including a screening period of up to 42 days) and consisted of a 12-week Treatment Period and a 24-week Post-Treatment Period for all participants who received study drugs.
Interventions
Tablet; paritaprevir co-formulated with ritonavir and ombitasvir
DRUGDasabuvir
Tablet
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Chronic HCV genotype 1-infection prior to study enrollment. Chronic HCV-infection is defined as the following: * Positive for anti-HCV antibody (Ab) or HCV RNA \> 1,000 IU/mL at least 6 months before Screening, and positive for HCV RNA and anti-HCV Ab at the time of Screening; or * HCV RNA \> 1,000 IU/mL at the time of Screening with a liver biopsy consistent with chronic HCV-infection (or a liver biopsy performed prior to enrollment with evidence of chronic hepatitis C disease). 2. Screening laboratory result indicating HCV genotype 1b-infection. 3. Compensated cirrhosis defined as a Child-Pugh Score of 5 or 6 at Screening.
Exclusion criteria
1. Women who are pregnant or breastfeeding. 2. Positive test result for Hepatitis B surface antigen (HBsAg) or positive human immunodeficiency virus (HIV) antibody (confirmed by Western Blot). 3. Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation such as ascites (noted on physical exam), variceal bleeding, or hepatic encephalopathy. 4. Confirmed presence of hepatocellular carcinoma indicated on imaging techniques such as computed tomography (CT) scan or magnetic resonance imaging (MRI) within 3 months prior to Screening or on an ultrasound performed at Screening (a positive ultrasound result will be confirmed with CT scan or MRI.) 5. Use of contraindicated medications within 2 weeks of dosing 6. Screening laboratory analyses showing any of the following abnormal laboratory results: * Calculated creatinine clearance (using Cockcroft-Gault method) \< 30 mL/min * Albumin \< 2.8 g/dL * International normalized ratio (INR) \> 1.8. Participants with a known inherited blood disorder and INR \> 1.8 may be enrolled with permission of the AbbVie Study Designated Physician. * Hemoglobin \< 10 g/dL * Platelets \< 25,000 cells per mm3 * Total bilirubin \> 3.0 mg/dL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment | Post-treatment Day 1 to Post-treatment Week 12 | Sustained Virologic Response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (\< LLOQ; \< 25 IU/mL) 12 weeks after the last dose of study drug. The primary efficacy endpoints were non-inferiority and superiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm compared with the historical threshold for sofosbuvir and peginterferon (pegIFN)/RBV for the treatment of subjects with HCV GT1b infection and cirrhosis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-Treatment Virologic Failure | Day 1 through Week 12 | On-Treatment Virologic Failure is defined as confirmed HCV RNA \>= LLOQ after HCV RNA \< LLOQ during treatment, or confirmed increase from nadir (local minimum value) in HCV RNA \[2 consecutive HCV RNA measurements \> 1 log10 IU/mL above nadir\] at any time point during treatment, or failure to suppress during treatment \[all on-treatment values of HCV RNA \>= LLOQ\] with at least 6 weeks \[defined as active study drug duration ≥ 36 days\] of treatment. |
| Percentage of Participants With Post-Treatment Relapse | Post-treatment Day 1 to Post-treatment Week 12 | Post- Treatment Relapse is defined as confirmed HCV RNA \>= LLOQ between end of treatment and 12 weeks after last actual dose of active study drug \[up to and including the SVR12 assessment time point\] for a participant with HCV RNA \< LLOQ at Final Treatment Visit who completes treatment. |
Participant flow
Recruitment details
A total of 60 subjects were enrolled and all the subjects completed the study. All 60 subjects were analyzed for both efficacy (included all participants who received at least 1 dose of study drug (ITT)) and safety.
Participants by arm
| Arm | Count |
|---|---|
| Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) administered for 12 weeks. | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir |
|---|---|
| Age, Continuous | 59.5 years STANDARD_DEVIATION 9.53 |
| Interleukin 28B (IL28B) Genotype CC | 10 participants |
| Interleukin 28B (IL28B) Genotype CT | 36 participants |
| Interleukin 28B (IL28B) Genotype Missing | 0 participants |
| Interleukin 28B (IL28B) Genotype TT | 14 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 60 |
| serious Total, serious adverse events | 1 / 60 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment
Sustained Virologic Response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (\< LLOQ; \< 25 IU/mL) 12 weeks after the last dose of study drug. The primary efficacy endpoints were non-inferiority and superiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm compared with the historical threshold for sofosbuvir and peginterferon (pegIFN)/RBV for the treatment of subjects with HCV GT1b infection and cirrhosis.
Time frame: Post-treatment Day 1 to Post-treatment Week 12
Population: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir | Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment | 100 percentage of participants |
95% CI: [94, 100]
Comparison: The superiority of the Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir regimen in SVR12 to a historical threshold for sofosbuvir plus pegIFN/ ribavirin (RBV) for the treatment of participants with HCV Genotype 1b (GT1b) infection and cirrhosis was calculated using a 2-sided 95% CI from Wilson's score method. Superiority was declared if the lower confidence bound was greater than 83.2%.95% CI: [94, 100]
Secondary
Percentage of Participants With On-Treatment Virologic Failure
On-Treatment Virologic Failure is defined as confirmed HCV RNA \>= LLOQ after HCV RNA \< LLOQ during treatment, or confirmed increase from nadir (local minimum value) in HCV RNA \[2 consecutive HCV RNA measurements \> 1 log10 IU/mL above nadir\] at any time point during treatment, or failure to suppress during treatment \[all on-treatment values of HCV RNA \>= LLOQ\] with at least 6 weeks \[defined as active study drug duration ≥ 36 days\] of treatment.
Time frame: Day 1 through Week 12
Population: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir | Percentage of Participants With On-Treatment Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants With Post-Treatment Relapse
Post- Treatment Relapse is defined as confirmed HCV RNA \>= LLOQ between end of treatment and 12 weeks after last actual dose of active study drug \[up to and including the SVR12 assessment time point\] for a participant with HCV RNA \< LLOQ at Final Treatment Visit who completes treatment.
Time frame: Post-treatment Day 1 to Post-treatment Week 12
Population: Efficacy analyses included all participants who received at least 1 dose of study drug (ITT).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir | Percentage of Participants With Post-Treatment Relapse | 0 percentage of participants |