Hepatitis C Virus (HCV)
Conditions
Keywords
HCV Infection, Chronic Hepatitis C Virus, Hepatitis C Virus (HCV) Genotype 1b
Brief summary
This is a study to evaluate ABT 450/r/ABT-267 and ABT-333 in treatment-naïve and treatment-experienced Asian adults with subgenotype 1b chronic HCV without cirrhosis.
Interventions
Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet
DRUGPlacebo for ombitasvir/paritaprevir/ritonavir and dasabuvir
Placebo for ombitasvir/paritaprevir/ritonavir and dasabuvir
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Chinese, South Korean, and Taiwanese descent with full Chinese, South Korean, and Taiwanese parentage * Chronic hepatitis C virus (HCV) infection prior to study enrollment. * Screening laboratory result indicating HCV subtype 1b (GT1b) infection. * Per local standard practice, documented absence of cirrhosis. * Participant has never received antiviral treatment (including interferon \[IFN\]-based therapy \[alpha, beta or pegylated (peg)IFN\] with or without RBV) for HCV infection (treatment-naïve participant) or participant must have documentation that they met the definition of one of the following categories (treatment experienced participant): Non-responder or Relapser * Participant has plasma HCV RNA level \> 10,000 IU/mL at Screening.
Exclusion criteria
* HCV genotype performed during screening indicating unable to genotype or infection with any HCV genotype other than GT1b. * Positive test result at Screening for hepatitis B surface antigen (HBsAg), or hepatitis B virus DNA (HBV-DNA) \> Lower Limit of Quantification (LLOQ) if HBsAg negative, or anti-human immunodeficiency virus antibody (HIV Ab) positive. * Any current or past clinical evidence of cirrhosis. * Any primary cause of liver disease other than chronic HCV infection. * Screening laboratory analyses showing abnormal kidney, hepatic, or hematologic function. * Use of known strong inducers of cytochrome P450 3A (CYP3A) or strong inhibitors of cytochrome P450 3A (CYP2C8) within 2 weeks or within 10 half-lives, whichever is longer, of the respective medication/supplement prior to study drug administration.
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 active 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 active study drug. The primary efficacy endpoint was superiority of the percentage of treatment-naïve and treatment-experienced HCV subgenotype 1b (GT1b)-infected participants treated with 3-DAA (ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 once daily\] and dasabuvir \[250 mg twice daily\]) who achieved SVR12 compared with the historical control rate for comparable patients treated with telaprevir (TVR) plus pegylated interferon (pegIFN) and RBV. |
| Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 24 weeks after the last actual dose of active study drug | SVR24 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 active study drug. The primary efficacy endpoint was superiority of the percentage of treatment-naïve and treatment-experienced HCV subgenotype 1b (GT1b)-infected participants treated with 3-DAA (ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 once daily\] and dasabuvir \[250 mg twice daily\]) who achieved SVR24 compared with the historical control rate for comparable patients treated with telaprevir (TVR) plus pegylated interferon (pegIFN) and RBV. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Failure | up to 12 weeks | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during active treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during active treatment; or all on-treatment values of HCV RNA ≥ LLOQ with at least 6 weeks of active treatment. |
| Percentage of Participants With Post-treatment Relapse by Post-treatment Week 12 | From the end of treatment through 12 weeks after the last dose of active 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 active study drug among participants who completed treatment with HCV RNA levels \< LLOQ at the end of treatment. |
| Percentage of Participants With Post-treatment Relapse by Post-treatment Week 24 | From the end of treatment through 24 weeks after the last dose of active study drug | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 24 weeks after the last dose of active study drug among participants who completed treatment with HCV RNA levels \< LLOQ at the end of treatment. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Double-blind 3-DAA Double-blind 3-DAA (ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 mg once daily\] and dasabuvir \[250 mg twice daily\]) for 12 weeks. | 325 |
| Double-blind Placebo Followed by Open-label 3-DAA Double-blind placebo for 12 weeks, followed by open-label 3-DAA (ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 mg once daily\] and dasabuvir \[250 mg twice daily\]) for 12 weeks. | 325 |
| Total | 650 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrew Consent | 0 | 1 |
Baseline characteristics
| Characteristic | Double-blind 3-DAA | Double-blind Placebo Followed by Open-label 3-DAA | Total |
|---|---|---|---|
| Age, Continuous | 46.8 years STANDARD_DEVIATION 13.84 | 45.6 years STANDARD_DEVIATION 14.05 | 46.2 years STANDARD_DEVIATION 13.95 |
| Sex: Female, Male Female | 175 Participants | 177 Participants | 352 Participants |
| Sex: Female, Male Male | 150 Participants | 148 Participants | 298 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 | 72 / 325 | 61 / 325 | 55 / 324 |
| serious Total, serious adverse events | 7 / 325 | 2 / 325 | 5 / 324 |
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 active study drug. The primary efficacy endpoint was superiority of the percentage of treatment-naïve and treatment-experienced HCV subgenotype 1b (GT1b)-infected participants treated with 3-DAA (ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 once daily\] and dasabuvir \[250 mg twice daily\]) who achieved SVR12 compared with the historical control rate for comparable patients treated with telaprevir (TVR) plus pegylated interferon (pegIFN) and RBV.
Time frame: 12 weeks after the last actual dose of active study drug
Population: All treatment-naïve and treatment-experienced participants who received at least 1 dose of active study drug; participants with missing data after backward imputation were counted as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind 3-DAA (Treatment-Naïve) | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 99.5 percentage of participants |
| Double-blind 3-DAA (Treatment-Experienced) | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
Comparison: Based on a 2-sided significance level of 0.05 and an underlying rate of 96% for the Double-blind 3-DAA treatment-naïve group, the sample size 180 treatment-naïve participants provided \>90% power to demonstrate superiority of the regimen to the historical rate for treatment-naïve patients treated with TVR + pegIFN + RBV (80%) (based on one-sample chi-square test of a single binomial proportion for superiority).95% CI: [97, 99.9]
Comparison: Based on a 2-sided significance level of 0.05 and an underlying rate of 96% for the Double-blind 3-DAA treatment-experienced group, the sample size 180 treatment-experienced participants provided \>90% power to demonstrate superiority of the regimen to the historical rate for treatment-experienced patients treated with TVR + pegIFN + RBV (80%) (based on one-sample chi-square test of a single binomial proportion for superiority).95% CI: [97.4, 100]
Primary
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 \[\<LLOQ\]) 12 weeks after the last dose of active study drug. The primary efficacy endpoint was superiority of the percentage of treatment-naïve and treatment-experienced HCV subgenotype 1b (GT1b)-infected participants treated with 3-DAA (ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 once daily\] and dasabuvir \[250 mg twice daily\]) who achieved SVR24 compared with the historical control rate for comparable patients treated with telaprevir (TVR) plus pegylated interferon (pegIFN) and RBV.
Time frame: 24 weeks after the last actual dose of active study drug
Population: All treatment-naïve and treatment-experienced participants who received at least 1 dose of active study drug; participants with missing data after backward imputation were counted as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind 3-DAA (Treatment-Naïve) | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 99.5 percentage of participants |
| Double-blind 3-DAA (Treatment-Experienced) | Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | 100 percentage of participants |
Comparison: Based on a 2-sided significance level of 0.05 and an underlying rate of 96% for the Double-blind 3-DAA treatment-experienced group, the sample size 180 treatment-experienced participants provided \>90% power to demonstrate superiority of the regimen to the historical rate for treatment-experienced patients treated with TVR + pegIFN + RBV (80%) (based on one-sample chi-square test of a single binomial proportion for superiority).95% CI: [97, 99.9]
Comparison: Based on a 2-sided significance level of 0.05 and an underlying rate of 96% for the Double-blind 3-DAA treatment-experienced group, the sample size 180 treatment-experienced participants provided \>90% power to demonstrate superiority of the regimen to the historical rate for treatment-experienced patients treated with TVR + pegIFN + RBV (80%) (based on one-sample chi-square test of a single binomial proportion for superiority).95% CI: [97.4, 100]
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during active treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during active treatment; or all on-treatment values of HCV RNA ≥ LLOQ with at least 6 weeks of active treatment.
Time frame: up to 12 weeks
Population: All participants who received at least 1 dose of active study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind 3-DAA (Treatment-Naïve) | Percentage of Participants With On-treatment Virologic Failure | 1.1 percentage of participants |
| Double-blind 3-DAA (Treatment-Experienced) | Percentage of Participants With On-treatment Virologic Failure | 0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse by Post-treatment Week 12
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of active 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 active study drug
Population: All participants who received at least 1 dose of active study drug, completed treatment, and had HCV RNA \<LLOQ at the final treatment visit, who had HCV RNA data available during the SVR12 period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind 3-DAA (Treatment-Naïve) | Percentage of Participants With Post-treatment Relapse by Post-treatment Week 12 | 0 percentage of participants |
| Double-blind 3-DAA (Treatment-Experienced) | Percentage of Participants With Post-treatment Relapse by Post-treatment Week 12 | 0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse by Post-treatment Week 24
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 24 weeks after the last dose of active 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 24 weeks after the last dose of active study drug
Population: All participants who received at least 1 dose of active study drug, completed treatment, and had HCV RNA \<LLOQ at the final treatment visit, who had HCV RNA data available during the SVR24 period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-blind 3-DAA (Treatment-Naïve) | Percentage of Participants With Post-treatment Relapse by Post-treatment Week 24 | 0 percentage of participants |
| Double-blind 3-DAA (Treatment-Experienced) | Percentage of Participants With Post-treatment Relapse by Post-treatment Week 24 | 0 percentage of participants |