Chronic Hepatitis C, Hepatitis C (HCV), Hepatitis C Genotype 1a
Conditions
Keywords
Treatment naive, HCV, Interferon free, Hepatitis C Genotype 1a, Chronic Hepatitis C, Hepatitis C
Brief summary
To evaluate the effect of ribavirin on second phase plasma hepatitis C virus (HCV) ribonucleic acid (RNA) decline in participants who receive ombitasvir/ABT-450/ritonavir and dasabuvir with full dose ribavirin, low dose ribavirin or without ribavirin for 2 weeks in treatment-naive HCV genotype (GT) 1a-infected adults.
Interventions
DRUGOmbitasvir/ABT-450/Ritonavir
Ombitasvir/ABT-450/ritonavir combination tablets
DRUGDasabuvir
Dasabuvir tablets
DRUGRibavirin (RBV)
Ribavirin tablets
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
1. Screening laboratory result indicating HCV genotype 1 (GT1) a infection. 2. Chronic HCV infection. 3. Subjects must be non-cirrhotic. 4. Subjects must be able to understand and adhere to the study visit schedule and all protocol requirements as well as voluntarily sign and date an institutional review board (IRB) approved informed consent.
Exclusion criteria
1. Women who are pregnant or breastfeeding. 2. Positive test result for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) positive immunoassay. 3. Clinically significant abnormalities or co-morbidities, other than HCV infection, that make the subject unsuitable for this study or treatment. 4. Current enrollment in another interventional clinical study. Previous use of any HCV treatments including pegylated interferon (pegIFN), ribavirin, or any direct acting antiviral agent, either investigational or approved, for HCV including protease inhibitors, nucleoside or non-nucleoside polymerase inhibitors, or nonstructural viral protein 5A (NS5A) inhibitors. 5. History or solid organ transplant. 6. Screening laboratory analysis that shows abnormal results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Slope of the Second Phase Decline in Plasma HCV Ribonucleic Acid (RNA) Levels During Treatment | From Week 0 to Week 2 | HCV viral kinetics in plasma during therapy were modeled through non-linear mixed effect models, including a rapid first phase of initial decline and a slower second phase decline. The slope of the second phase decline was estimated for each treatment arm. |
Participant flow
Recruitment details
This study was conducted at one clinic in France and one clinic in the United States. Participants were treatment-naïve adults with hepatitis C virus (HCV) genotype (GT)1a infection without cirrhosis.
Pre-assignment details
Participants were randomized to Arms A or B in a 1:1 ratio first, and once those arms fully enrolled, Arm C was enrolled. Randomization to Arms A and B was stratified by site.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Ribavirin Full Dose for Last 10 Weeks Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) for 12 weeks and weight-based ribavirin (1000 mg or 1200 mg split BID) for the last 10 weeks. | 21 |
| Arm B: Ribavirin Full Dose for 12 Weeks Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and weight-based ribavirin (1000 mg or 1200 mg split BID) for 12 weeks. | 19 |
| Arm C: Ribavirin Low-dose for 12 Weeks Participants received ombitasvir/ABT-450/ritonavir 25 mg/150 mg/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) and 600 mg ribavirin once daily for 12 weeks. | 6 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 0 |
| Overall Study | Non-compliance | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Arm A: Ribavirin Full Dose for Last 10 Weeks | Arm B: Ribavirin Full Dose for 12 Weeks | Arm C: Ribavirin Low-dose for 12 Weeks | Total |
|---|---|---|---|---|
| Age, Continuous | 44.9 years STANDARD_DEVIATION 11.96 | 46.0 years STANDARD_DEVIATION 12.78 | 36.7 years STANDARD_DEVIATION 15.79 | 44.3 years STANDARD_DEVIATION 12.88 |
| Age, Customized ≥ 55 - 65 years | 4 Participants | 5 Participants | 1 Participants | 10 Participants |
| Age, Customized < 55 years | 17 Participants | 14 Participants | 5 Participants | 36 Participants |
| Age, Customized ≥ 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black of African American | 4 Participants | 3 Participants | 1 Participants | 8 Participants |
| Race/Ethnicity, Customized Mutli Race | 1 Participants | 2 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 16 Participants | 14 Participants | 4 Participants | 34 Participants |
| Sex: Female, Male Female | 11 Participants | 12 Participants | 4 Participants | 27 Participants |
| Sex: Female, Male Male | 10 Participants | 7 Participants | 2 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 17 / 21 | 16 / 19 | 6 / 6 |
| serious Total, serious adverse events | 1 / 21 | 0 / 19 | 0 / 6 |
Outcome results
Primary
Slope of the Second Phase Decline in Plasma HCV Ribonucleic Acid (RNA) Levels During Treatment
HCV viral kinetics in plasma during therapy were modeled through non-linear mixed effect models, including a rapid first phase of initial decline and a slower second phase decline. The slope of the second phase decline was estimated for each treatment arm.
Time frame: From Week 0 to Week 2
Population: Participants with evaluable HCV RNA to calculate the slope of the second phase. Three participants were excluded due to algorithm non-convergence in the non-linear modeling process.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: Ribavirin Full Dose for Last 10 Weeks | Slope of the Second Phase Decline in Plasma HCV Ribonucleic Acid (RNA) Levels During Treatment | 0.0036 1/day |
| Arm B: Ribavirin Full Dose for 12 Weeks | Slope of the Second Phase Decline in Plasma HCV Ribonucleic Acid (RNA) Levels During Treatment | 0.0046 1/day |
| Arm C: Ribavirin Low-dose for 12 Weeks | Slope of the Second Phase Decline in Plasma HCV Ribonucleic Acid (RNA) Levels During Treatment | 0.0051 1/day |
p-value: 0.311Wilcoxon Rank Sum Test
p-value: 0.561Wilcoxon Rank Sum Test