Chronic Hepatitis C Virus (HCV) Infection
Conditions
Keywords
Chronic Hepatitis C, Hepatitis C, Hepatitis C Virus, Hepatitis C Genotype 1b, Interferon-Free
Brief summary
This was a multicenter study evaluating the efficacy and safety of ombitasvir/paritaprevir/ritonavir and dasabuvir co-administered with ribavirin (RBV) for 12 weeks in treatment naïve and pegylated-interferon alfa-2a or alfa-2b (pegIFN)/RBV treatment-experienced, cirrhotic HCV genotype 1b-infected adults.
Detailed description
The primary objective of this study was to assess the safety and efficacy (the percentage of participants achieving a 12-week sustained virologic response (SVR12), \[HCV ribonucleic acid (RNA) \< lower limit of quantification (LLOQ) 12 weeks following treatment\]) of co-formulated ombitasvir, paritaprevir, and ritonavir (ombitasvir/paritaprevir/r) and dasabuvir co-administered with RBV for 12 weeks in HCV genotype 1b-infected adult participants with compensated cirrhosis. The secondary objectives of this study were to assess the number and percentage of participants with virologic failure during treatment and the percentage of participants with relapse post-treatment.
Interventions
Tablet; paritaprevir co-formulated with ritonavir and ombitasvir
DRUGDasabuvir
Tablet
DRUGRibavirin (RBV)
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
* Chronic hepatitis C, genotype 1b-infection (HCV RNA level greater than 1,000 IU/mL at Screening) * Evidence of liver cirrhosis as confirmed by liver biopsy or Fibroscan with Child-Pugh score less than or equal to 6 at Screening * Participant had never received antiviral treatment (including pegIFN/RBV) for hepatitis C infection (treatment-naïve participant) or had documentation of meeting one of the defined categories of a treatment-experienced participants * Absence of hepatocellular carcinoma (HCC) as indicated by a negative ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) performed within 3 months prior to screening or a negative ultrasound at screening. * Females must be post-menopausal, of non-child bearing potential or practicing specific forms of birth control * Males must have been surgically sterile, or agreed to practice 2 effective methods of birth control throughout the course of the study.
Exclusion criteria
* Positive screen for hepatitis B Surface antigen or anti-Human Immunodeficiency virus antibody * Evidence of current or past Child-Pugh B or C classification * Confirmed presence of hepatocellular carcinoma * Abnormal laboratory tests * Participant who self-reported on average drinking more than 2 drinks per day for current drinkers * Previous treatment with a direct acting antiviral agent (DAA) containing regimen * History of solid organ transplant.
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. Participants with missing data were imputed as failures. |
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 36 participants were enrolled and all the participants completed the study. All 36 participants 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 With RBV Ombitasvir/Paritaprevir/Ritonavir (25/150/100 mg once daily) and Dasabuvir (250 mg twice daily) co-administered with weight-based Ribavirin (RBV; twice daily) for 12 weeks. | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | Ombitasvir/Paritaprevir/Ritonavir Plus Dasabuvir With RBV |
|---|---|
| Age, Continuous | 51.6 years STANDARD_DEVIATION 7.91 |
| Interleukin 28B (IL28B) CC | 4 participants |
| Interleukin 28B (IL28B) CT | 25 participants |
| Interleukin 28B (IL28B) Missing | 0 participants |
| Interleukin 28B (IL28B) TT | 7 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 21 / 36 |
| serious Total, serious adverse events | 0 / 36 |
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. Participants with missing data were imputed as failures.
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 With RBV | Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment | 100 percentage of participants |
95% CI: [90.4, 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 With RBV | 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 With RBV | Percentage of Participants With Post-Treatment Relapse | 0 percentage of participants |