Chronic Hepatitis C, Hepatitis C Virus, HCV
Conditions
Keywords
HCV GT1, Non-cirrhotic, RBV Free, Without cirrhosis, Chronic Hepatitis C, Hepatitis C Genotype 1 (GT1), IFN free, Hepatitis C, Ribavirin Free, Interferon (IFN) Free, HCV, Hepatitis C virus, DAA
Brief summary
This study seeks to evaluate the efficacy and safety of ABT-493/ABT-530 in participants with Genotype 1 hepatitis C virus infection without cirrhosis
Interventions
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
* Male or female, at least 18 years of age at time of screening. * Screening laboratory result indicating hepatitis C virus (HCV) genotype 1 (GT1) infection. * Chronic HCV infection. * Subject must be HCV treatment-naïve (i.e., patient has never received a single dose of any approved or investigational regimen) or treatment-experienced (has failed prior interferon \[IFN\] or pegylated IFN (pegIFN) with or without ribivarin (RBV), or sofosbuvir (SOF) plus RBV with or without pegIFN therapy). * Subjects must be non-cirrhotic. Additional Inclusion Criteria for HCV GT1/human immununovirus type 1 (HIV-1) co-infected patients: * HIV-1 antiretroviral treatment (ART) naïve with CD4 ≥ 500 cells/mm3 (or CD4+ % ≥ 29%) at Screening and plasma HIV-1 RNA \<1,000 copies/mL at Screening and at least once during the 12 months prior to Screening. OR * On a stable, qualifying HIV-1 ART regimen for at least 8 weeks prior to screening, with CD4 ≥ 200 cells/mm3 (or CD4+ % ≥14%) at Screening and plasma HIV-1 RNA \< LLOQ at Screening and at least once during the 12 months prior to Screening.
Exclusion criteria
* History of severe, life-threatening or other significant sensitivity to any excipients 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). * HCV genotype performed during screening indicating co-infection with more than one HCV genotype. * Chronic HIV type 2 (HIV-2) infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Mono-infected Hepatitis C Virus Genotype 1 (HCV GT1), Direct-acting Antiviral Agent (DAA) Naïve Participants in the 12-Week Treatment Arm | 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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in the 12-week treatment group compared with the historical control rate for HCV GT1 subjects who are treatment-naïve or treated with pegylated-interferon alfa-2a or alfa-2b and ribavirin (pegIFN/RBV). |
| Percentage of Participants With SVR12: Noninferiority of 8-Week Arm to 12-Week Arm in Mono-infected HCV GT1, DAA-Naïve Participants, Excluding Those Who Discontinued/Experienced Virologic Failure by Week 8 or Had No HCV RNA Value at Week 12 or Later | 12 weeks after last actual dose of study drug | SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants (excluding those who discontinued/experienced virologic failure by Week 8 or had no HCV RNA value at Week 12 or later) who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm. |
| Percentage of Participants With SVR12: Noninferiority of 8-Week Treatment Arm to 12-Week Treatment Arm in Mono-infected HCV GT1, DAA-Naïve Participants | 12 weeks after the last actual dose of study drug | SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With SVR12 in Mono-infected HCV GT1 Participants | 12 weeks after last actual dose of study drug | SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. |
| Percentage of Participants With SVR12 | 12 weeks after last actual dose of study drug | SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. |
| Percentage of Participants With SVR12 in Co-infected HCV GT1/Human Immunodeficiency Virus Type 1 (HIV-1) Participants | 12 weeks after last actual dose of study drug | SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. |
| Percentage of Participants With SVR12 in HCV GT1-infected, Prior Sofosbuvir (SOF) Treatment-Experienced Participants | 12 weeks after last actual dose of study drug | SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. |
| Percentage of Participants With On-treatment Virologic Failure | Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment | On-treatment virologic failure was defined as confirmed increase of \>1 log(subscript)10(subscript) IU/mL above the lowest value 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 On-treatment Virologic Failure in Mono-infected HCV GT1, DAA-Naïve Participants | Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment | On-treatment virologic failure was defined as confirmed increase of \>1 log(subscript)10(subscript) IU/mL above the lowest value 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 | 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 who completed treatment with HCV RNA levels \<LLOQ at the end of treatment, excluding reinfection. |
| Percentage of Participants With Post-treatment Relapse in Mono-infected HCV GT1, DAA-Naïve Participants | 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 who completed treatment with HCV RNA levels \<LLOQ at the end of treatment, excluding reinfection. |
Participant flow
Pre-assignment details
This study included a 35-day screening period.
Participants by arm
| Arm | Count |
|---|---|
| ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. | 352 |
| ABT-493/ABT-530 for 8 Weeks ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks. | 351 |
| Total | 703 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 5 | 6 |
| Overall Study | Other | 1 | 0 |
| Overall Study | Withdrew Consent | 0 | 2 |
Baseline characteristics
| Characteristic | ABT-493/ABT-530 for 12 Weeks | ABT-493/ABT-530 for 8 Weeks | Total |
|---|---|---|---|
| Age, Continuous | 50.27 years STANDARD_DEVIATION 11.62 | 51.58 years STANDARD_DEVIATION 11.9 | 50.93 years STANDARD_DEVIATION 11.77 |
| Sex: Female, Male Female | 176 Participants | 184 Participants | 360 Participants |
| Sex: Female, Male Male | 176 Participants | 167 Participants | 343 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 130 / 352 | 133 / 351 |
| serious Total, serious adverse events | 4 / 352 | 5 / 351 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Mono-infected Hepatitis C Virus Genotype 1 (HCV GT1), Direct-acting Antiviral Agent (DAA) Naïve Participants in the 12-Week Treatment Arm
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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in the 12-week treatment group compared with the historical control rate for HCV GT1 subjects who are treatment-naïve or treated with pegylated-interferon alfa-2a or alfa-2b and ribavirin (pegIFN/RBV).
Time frame: 12 weeks after the last actual dose of study drug
Population: All participants in the ITT population who were mono-infected HCV GT1, DAA-naïve; participants with missing data after backwards imputation were imputed as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Mono-infected Hepatitis C Virus Genotype 1 (HCV GT1), Direct-acting Antiviral Agent (DAA) Naïve Participants in the 12-Week Treatment Arm | 99.7 percentage of participants |
Comparison: Based on a 2-sided significance level of 0.05 and an underlying rate of ≥97% in the 12-week arm, 270 participants provides \>90% power to demonstrate noninferiority of the 12-week arm to the historical control rate for HCV GT1 subjects who are treatment-naïve or treated with pegIFN/RBV (based on the normal approximation of a single binomial proportion in a one-sample test for superiority).95% CI: [99.1, 100]
Primary
Percentage of Participants With SVR12: Noninferiority of 8-Week Arm to 12-Week Arm in Mono-infected HCV GT1, DAA-Naïve Participants, Excluding Those Who Discontinued/Experienced Virologic Failure by Week 8 or Had No HCV RNA Value at Week 12 or Later
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants (excluding those who discontinued/experienced virologic failure by Week 8 or had no HCV RNA value at Week 12 or later) who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm.
Time frame: 12 weeks after last actual dose of study drug
Population: All participants in the ITT population who were mono-infected HCV GT1 DAA-naïve (excluding those who discontinued/experienced virologic failure by Week 8 or had no HCV RNA value at Week 12 or later); participants with missing data after backwards imputation were imputed as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With SVR12: Noninferiority of 8-Week Arm to 12-Week Arm in Mono-infected HCV GT1, DAA-Naïve Participants, Excluding Those Who Discontinued/Experienced Virologic Failure by Week 8 or Had No HCV RNA Value at Week 12 or Later | 100.0 percentage of participants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With SVR12: Noninferiority of 8-Week Arm to 12-Week Arm in Mono-infected HCV GT1, DAA-Naïve Participants, Excluding Those Who Discontinued/Experienced Virologic Failure by Week 8 or Had No HCV RNA Value at Week 12 or Later | 100 percentage of participants |
Comparison: Based on a 2-sided significance level of 0.05 and an -5% noninferiority margin and an underlying rate of ≥97% in the 8-week arm (270 participants) and ≥97% in the 12-week arm (270 participants) provides \>90% power to demonstrate noninferiority of the 8-week arm to the 12-week arm.95% CI: [-1.1, 1.1]
Primary
Percentage of Participants With SVR12: Noninferiority of 8-Week Treatment Arm to 12-Week Treatment Arm in Mono-infected HCV GT1, DAA-Naïve Participants
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm.
Time frame: 12 weeks after the last actual dose of study drug
Population: All participants in the ITT population who were mono-infected HCV GT1, DAA-naïve; participants with missing data after backwards imputation were imputed as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With SVR12: Noninferiority of 8-Week Treatment Arm to 12-Week Treatment Arm in Mono-infected HCV GT1, DAA-Naïve Participants | 99.7 percentage of participants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With SVR12: Noninferiority of 8-Week Treatment Arm to 12-Week Treatment Arm in Mono-infected HCV GT1, DAA-Naïve Participants | 99.1 percentage of participants |
Comparison: Based on a 2-sided significance level of 0.05 and a -5% noninferiority margin, and an underlying rate of ≥97% in the 8-week arm (270 participants) and ≥97% in the 12-week arm (270 participants) provides \>90% power to demonstrate noninferiority of the 8-week arm to the 12-week arm.95% CI: [-1.8, 0.6]
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed increase of \>1 log(subscript)10(subscript) IU/mL above the lowest value 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: Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-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) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With On-treatment Virologic Failure | 0.0 percentage of particpants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With On-treatment Virologic Failure | 0.3 percentage of particpants |
Secondary
Percentage of Participants With On-treatment Virologic Failure in Mono-infected HCV GT1, DAA-Naïve Participants
On-treatment virologic failure was defined as confirmed increase of \>1 log(subscript)10(subscript) IU/mL above the lowest value 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: Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment
Population: All participants in the ITT population who were mono-infected HCV GT1, DAA-naïve.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With On-treatment Virologic Failure in Mono-infected HCV GT1, DAA-Naïve Participants | 0.0 percentage of participants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With On-treatment Virologic Failure in Mono-infected HCV GT1, DAA-Naïve Participants | 0.3 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 who completed treatment 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) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With Post-treatment Relapse | 0.0 percentage of participants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With Post-treatment Relapse | 0.0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse in Mono-infected HCV GT1, DAA-Naïve Participants
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 who completed treatment 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 in the ITT population who were mono-infected HCV GT1, DAA-naïve, received at least 1 dose of study drug, completed treatment, and had HCV RNA \<LLOQ at the final treatment visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With Post-treatment Relapse in Mono-infected HCV GT1, DAA-Naïve Participants | 0.0 percentage of participants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With Post-treatment Relapse in Mono-infected HCV GT1, DAA-Naïve Participants | 0.0 percentage of participants |
Secondary
Percentage of Participants With SVR12
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug.
Time frame: 12 weeks after last actual dose of study drug
Population: All participants in the ITT population; participants with missing data after backwards imputation were imputed as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With SVR12 | 99.7 percentage of participants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With SVR12 | 99.1 percentage of participants |
Secondary
Percentage of Participants With SVR12 in Co-infected HCV GT1/Human Immunodeficiency Virus Type 1 (HIV-1) Participants
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug.
Time frame: 12 weeks after last actual dose of study drug
Population: All participants in the ITT population who were co-infected HCV GT1/HIV-1; participants with missing data after backwards imputation were imputed as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With SVR12 in Co-infected HCV GT1/Human Immunodeficiency Virus Type 1 (HIV-1) Participants | 100.0 percentage of participants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With SVR12 in Co-infected HCV GT1/Human Immunodeficiency Virus Type 1 (HIV-1) Participants | 100.0 percentage of participants |
Secondary
Percentage of Participants With SVR12 in HCV GT1-infected, Prior Sofosbuvir (SOF) Treatment-Experienced Participants
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug.
Time frame: 12 weeks after last actual dose of study drug
Population: All participants in the ITT population who were HCV GT1-infected, prior SOF-treatment experienced; participants with missing data after backwards imputation were imputed as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With SVR12 in HCV GT1-infected, Prior Sofosbuvir (SOF) Treatment-Experienced Participants | 100.0 percentage of participants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With SVR12 in HCV GT1-infected, Prior Sofosbuvir (SOF) Treatment-Experienced Participants | 100.0 percentage of participants |
Secondary
Percentage of Participants With SVR12 in Mono-infected HCV GT1 Participants
SVR12 was defined as plasma HCV RNA level \<LLOQ 12 weeks after the last dose of study drug.
Time frame: 12 weeks after last actual dose of study drug
Population: All participants in the ITT population who were mono-infected HCV GT1; participants with missing data after backwards imputation were imputed as nonresponders.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ABT-493/ABT-530 for 12 Weeks | Percentage of Participants With SVR12 in Mono-infected HCV GT1 Participants | 99.7 percentage of participants |
| ABT-493/ABT-530 for 8 Weeks | Percentage of Participants With SVR12 in Mono-infected HCV GT1 Participants | 99.1 percentage of participants |