Chronic Hepatitis C, Hepatitis C Virus, HCV, Direct-Acting Antiviral Agent (DAA)-Experienced
Conditions
Keywords
Hepatitis C, HCV Genotype 6, HCV GT1, Interferon (IFN) free, HCV Genotype 5, HCV, HCV GT4, HCV Genotype 4, Chronic Hepatitis C, Chronic HCV, Hepatitis C Genotype 1, HCV GT5, HCV Genotype 1
Brief summary
The purpose of this study is to assess the efficacy and safety of ABT-493 and ABT-530 with or without ribavirin (RBV) in participants with chronic hepatitis C virus, (HCV)-infection who previously failed treatment with a direct acting antiviral (DAA)-containing regimen.
Interventions
DRUGABT-493, ABT-530
ABT-493 (tablet) dosed with ABT-530 (tablet)
DRUGribavirin (RBV)
Tablet
DRUGABT-493/ABT-530
Tablet; ABT-493 coformulated with ABT-530
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients from 18 to 70 years in Arms A, B, and C; patients 18 years of age or older in Arms D and E. 2. Previous treatment with DAA-containing regimen for chronic hepatitis C virus (HCV) infection resulting in either on-treatment virologic failure or post-treatment relapse 3. Chronic HCV genotype (GT) 1, 4, 5, or 6-infection (GT4-6 in Arms D and E)
Exclusion criteria
1. History of severe, life-threatening or other significant sensitivity to any drug 2. 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 3. Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could preclude adherence to the protocol 4. Positive for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) 5. Co-infection with more than one HCV genotype
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 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 study drug. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4) | 4 weeks after the last actual dose of study drug | SVR4 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 4 weeks after the last dose of study drug. |
| Percentage of Participants With On-treatment Virologic Failure | Day 3, Treatment Weeks 1, 2, 4, 6, 8, 10, 12 (end of treatment for 12-week treatment arms), and 16 (end of treatment for 16-week treatment arm) or premature discontinuation from treatment | On-treatment virologic failure was defined as confirmed HCV RNA ≥ 100 IU after HCV RNA \< LLOQ during treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment. |
| Percentage of Participants With Post-treatment Relapse | From the end of treatment through 12 weeks after the last dose of 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 study drug among participants with HCV RNA levels \< LLOQ at the end of treatment, excluding reinfection. |
Participant flow
Pre-assignment details
This study included a 42-day screening period.
Participants by arm
| Arm | Count |
|---|---|
| ARM A ABT-493 (200 mg) once daily (QD) co-administered with ABT-530 (80 mg) QD for 12 weeks in chronic HCV genotype 1- infected participants without cirrhosis. | 6 |
| ARM B ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD plus ribavirin (RBV) for 12 weeks in chronic HCV genotype 1- infected participants without cirrhosis. | 22 |
| ARM C ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 12 weeks in chronic HCV genotype 1- infected participants without cirrhosis. | 22 |
| ARM D ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks in HCV genotypes 1- or 4-6- infected participants with or without cirrhosis. | 44 |
| ARM E ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 16 weeks in HCV genotype 1- or 4-6- infected participants with or without cirrhosis. | 47 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 0 | 1 |
| Overall Study | Withdrew consent | 0 | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | ARM A | ARM B | ARM C | ARM D | ARM E | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 53.5 years STANDARD_DEVIATION 9.16 | 55.2 years STANDARD_DEVIATION 6.29 | 58.5 years STANDARD_DEVIATION 6.56 | 55.6 years STANDARD_DEVIATION 8.57 | 55.6 years STANDARD_DEVIATION 8.31 | 55.9 years STANDARD_DEVIATION 7.88 |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 4 Participants | 13 Participants | 14 Participants | 36 Participants |
| Sex: Female, Male Male | 3 Participants | 20 Participants | 18 Participants | 31 Participants | 33 Participants | 105 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 6 | 17 / 22 | 16 / 22 | 23 / 44 | 27 / 47 |
| serious Total, serious adverse events | 1 / 6 | 1 / 22 | 0 / 22 | 1 / 44 | 2 / 47 |
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 study drug.
Time frame: 12 weeks after the last actual dose of study drug
Population: Intent-to-treat population: all participants who received at least 1 dose of study drug; participants with missing data after backwards imputation were imputed as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARM A | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| ARM B | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 95.5 percentage of participants |
| ARM C | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 86.4 percentage of participants |
| ARM D | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 88.6 percentage of participants |
| ARM E | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 91.5 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed HCV RNA ≥ 100 IU after HCV RNA \< LLOQ during treatment; confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.
Time frame: Day 3, Treatment Weeks 1, 2, 4, 6, 8, 10, 12 (end of treatment for 12-week treatment arms), and 16 (end of treatment for 16-week treatment arm) or premature discontinuation from treatment
Population: All participants who received at least 1 dose of study drug (ITT population)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARM A | Percentage of Participants With On-treatment Virologic Failure | 0.0 percentage of participants |
| ARM B | Percentage of Participants With On-treatment Virologic Failure | 0.0 percentage of participants |
| ARM C | Percentage of Participants With On-treatment Virologic Failure | 4.5 percentage of participants |
| ARM D | Percentage of Participants With On-treatment Virologic Failure | 2.3 percentage of participants |
| ARM E | Percentage of Participants With On-treatment Virologic Failure | 8.5 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse
Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants with HCV RNA levels \< LLOQ at the end of treatment, excluding reinfection.
Time frame: From the end of treatment through 12 weeks after the last dose of study drug
Population: All participants who received at least 1 dose of study drug, completed treatment, and had HCV RNA \<LLOQ at the final treatment visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARM A | Percentage of Participants With Post-treatment Relapse | 0.0 percentage of participants |
| ARM B | Percentage of Participants With Post-treatment Relapse | 4.8 percentage of participants |
| ARM C | Percentage of Participants With Post-treatment Relapse | 0.0 percentage of participants |
| ARM D | Percentage of Participants With Post-treatment Relapse | 9.3 percentage of participants |
| ARM E | Percentage of Participants With Post-treatment Relapse | 0.0 percentage of participants |
Secondary
Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4)
SVR4 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification \[\<LLOQ\]) 4 weeks after the last dose of study drug.
Time frame: 4 weeks after the last actual dose of study drug
Population: All participants who received at least 1 dose of study drug (ITT population); participants with missing data after backwards imputation were imputed as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ARM A | Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4) | 100.0 percentage of participants |
| ARM B | Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4) | 95.5 percentage of participants |
| ARM C | Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4) | 95.5 percentage of participants |
| ARM D | Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4) | 90.9 percentage of participants |
| ARM E | Percentage of Participants With Sustained Virologic Response 4 Weeks Post-treatment (SVR4) | 91.5 percentage of participants |