Chronic Hepatitis C Virus (HCV) Infection
Conditions
Keywords
Treatment-Naive, Hepatitis C Virus Genotype 2, Sofosbuvir (SOF)-Experienced, Treatment-Experienced, Non-cirrhotic
Brief summary
The purpose of this study is to evaluate the safety and efficacy of ABT-493/ABT-530 in adults with genotype 2 chronic hepatitis C virus (HCV) infection.
Interventions
DRUGABT-493/ABT-530
Tablet; ABT-493 coformulated with ABT-530
DRUGPlacebo for ABT-493/ABT-530
tablet
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Screening laboratory result indicating hepatitis C virus (HCV) Genotype-2 (GT2) infection. * Chronic HCV infection. * Subject must be HCV treatment-naïve (subject had never received a single dose of any approved or investigational regimen) or had failed prior interferon (IFN) or pegylated-interferon (pegIFN) ± ribavirin (RBV) or sofosbuvir (SOF) + RBV ± pegIFN therapy. * Subject must be non-cirrhotic.
Exclusion criteria
* History of severe, life-threatening or other significant sensitivity to any excipient of the study drugs. * Female who is pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner is pregnant or planning to become pregnant during the study. * Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol in the opinion of the investigator. * Positive test result at Screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab). * HCV genotype performed during screening indicating coinfection with more than 1 HCV genotype.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Noninferiority Analysis | 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 the noninferiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior sofosbuvir (SOF) + ribavirin (RBV) ± pegylatedinterferon (pegIFN) failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR12 in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Superiority Analysis | 12 weeks after the last actual dose of active study drug | SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. The secondary efficacy endpoint was the superiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior SOF + RBV ± pegIFN failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks). As pre-specified in the study protocol, the primary outcome measure and the secondary outcome measure are not tested independently from each other. Rather, the two measures are ranked in a fixed sequential testing procedure that only if success was demonstrated for the primary outcome (i.e. non-inferiority test of Arm A SVR12 rate to the standard of care) did we test the first secondary outcome (i.e. superiority test of Arm A SVR12 rate to the standard of care). |
| Percentage of Participants With On-treatment Virologic Failure in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures | Up to Week 12 post baseline | On-treatment virologic failure was defined as confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value of post-baseline HCV RNA during treatment; confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< LLOQ during treatment, or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment. |
| Percentage of Participants With Post-treatment Relapse in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures | Between End of Treatment (Week 12) and 12 weeks after the last dose of Arm A DB active drug (up to Week 24) | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of DB 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, excluding reinfection. |
| Percentage of Participants With SVR12 in Arm A DB Active Drug With Prior SOF + RBV ± pegIFN Failure | 12 weeks after the last actual dose of active study drug | SVR12 was defined as HCV RNA level \<LLOQ 12 weeks after the last dose of active study drug. |
Participant flow
Recruitment details
Safety population: All participants who received at least one dose of study drug.
Pre-assignment details
A total of 304 subjects were randomized and 302 subjects received at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Arm A DB Active Drug ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (double-blind \[DB\] treatment period) | 202 |
| Arm B DB Placebo Then OL Active Drug Placebo for ABT-493/ABT-530 QD for 12 weeks (DB treatment period) followed by ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks (open-label \[OL\] treatment period) | 100 |
| Total | 302 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
Baseline characteristics
| Characteristic | Arm A DB Active Drug | Arm B DB Placebo Then OL Active Drug | Total |
|---|---|---|---|
| Age, Continuous | 56.77 years STANDARD_DEVIATION 12.79 | 57.60 years STANDARD_DEVIATION 12.04 | 57.04 years STANDARD_DEVIATION 12.53 |
| Sex: Female, Male Female | 104 Participants | 55 Participants | 159 Participants |
| Sex: Female, Male Male | 98 Participants | 45 Participants | 143 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 | 75 / 202 | 38 / 100 | 31 / 100 |
| serious Total, serious adverse events | 3 / 202 | 1 / 100 | 1 / 100 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Noninferiority Analysis
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 the noninferiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior sofosbuvir (SOF) + ribavirin (RBV) ± pegylatedinterferon (pegIFN) failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks).
Time frame: 12 weeks after the last actual dose of active study drug
Population: All randomized participants who received at least one dose of study drug in Arm A DB excluding participants with prior SOF + RBV ± pegIFN failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A DB Active Drug | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Noninferiority Analysis | 99.5 percentage of participants |
Comparison: Based on a 2-sided significance level of 0.05 and an underlying rate of ≥96% in the Arm A (180 participants) provides \>90% power to demonstrate noninferiority of ABT-493/ABT-530 to the historical rate for patients treated with the current standard of care (SOF + RBV for 12 weeks) (95%) (based on the normal approximation of using a single binomial proportion a one-sample test for superiority).95% CI: [98.5, 100]
Secondary
Percentage of Participants With On-treatment Virologic Failure in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures
On-treatment virologic failure was defined as confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value of post-baseline HCV RNA during treatment; confirmed HCV RNA ≥ 100 IU/mL after HCV RNA \< LLOQ during treatment, or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.
Time frame: Up to Week 12 post baseline
Population: All randomized participants who received at least one dose of study drug in Arm A DB excluding participants with prior SOF + RBV ± pegIFN failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A DB Active Drug | Percentage of Participants With On-treatment Virologic Failure in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures | 0.0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of DB 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, excluding reinfection.
Time frame: Between End of Treatment (Week 12) and 12 weeks after the last dose of Arm A DB active drug (up to Week 24)
Population: All randomized participants who received at least 1 dose of study drug in Arm A DB with HCV RNA \< LLOQ at the final treatment visit who completed the DB treatment, excluding participants with prior SOF + RBV ± pegIFN failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A DB Active Drug | Percentage of Participants With Post-treatment Relapse in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures | 0.0 percentage of participants |
Secondary
Percentage of Participants With SVR12 in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Superiority Analysis
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. The secondary efficacy endpoint was the superiority of the percentage of participants who achieved SVR12 in Arm A Double Blind (DB) Active Drug excluding prior SOF + RBV ± pegIFN failures compared with the historical control rate for patients treated with the current standard of care (SOF + RBV for 12 weeks). As pre-specified in the study protocol, the primary outcome measure and the secondary outcome measure are not tested independently from each other. Rather, the two measures are ranked in a fixed sequential testing procedure that only if success was demonstrated for the primary outcome (i.e. non-inferiority test of Arm A SVR12 rate to the standard of care) did we test the first secondary outcome (i.e. superiority test of Arm A SVR12 rate to the standard of care).
Time frame: 12 weeks after the last actual dose of active study drug
Population: All randomized participants who received at least one dose of study drug in Arm A DB excluding participants with prior SOF + RBV ± pegIFN failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A DB Active Drug | Percentage of Participants With SVR12 in Arm A DB Active Drug Excluding Prior SOF + Ribavirin (RBV) ± pegIFN Failures: Superiority Analysis | 99.5 percentage of participants |
Comparison: Based on a 2-sided significance level of 0.05 and an underlying rate of ≥96% in the Arm A (180 participants) provides \>90% power to demonstrate superiority of ABT-493/ABT-530 to the historical rate for patients treated with the current standard of care (SOF + RBV for 12 weeks) (95%) (based on the normal approximation of a single binomial proportion using a one-sample test for superiority).95% CI: [98.5, 100]
Secondary
Percentage of Participants With SVR12 in Arm A DB Active Drug With Prior SOF + RBV ± pegIFN Failure
SVR12 was defined as HCV RNA level \<LLOQ 12 weeks after the last dose of active study drug.
Time frame: 12 weeks after the last actual dose of active study drug
Population: All randomized participants who received at least one dose of study drug in Arm A DB with prior SOF + RBV ± pegIFN failures.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A DB Active Drug | Percentage of Participants With SVR12 in Arm A DB Active Drug With Prior SOF + RBV ± pegIFN Failure | 100 percentage of participants |