Chronic Hepatitis C Virus, Hepatitis C Virus
Conditions
Keywords
Hepatitis C Virus, Non-cirrhotic, Hepatitis C Genotype 2, Chronic Hepatitis C Virus, Hepatitis C
Brief summary
The purpose of this phase 3 study is to evaluate the efficacy and safety of ABT-493/ABT-530 in comparison to sofosbuvir plus ribavirin for 12 weeks in Hepatitis C Virus (HCV) Genotype 2 (GT2) infected participants.
Detailed description
This was a randomized, open-label, active-control, multicenter study to evaluate efficacy, safety, and pharmacokinetics of ABT-493/ABT-530 in chronic HCV GT2-infected direct-acting antiviral agent (DAA) treatment-naïve Japanese adult participants without cirrhosis. The participants were randomized in a 2:1 ratio to ABT-493/ABT-530 for 8 weeks (Arm A) and sofosbuvir plus ribavirin for 12 weeks (Arm B).
Interventions
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
* Females were postmenopausal for at least 2 years prior to screening; surgically sterile or had a vasectomized partner; or, if of childbearing potential and sexually active with a male partner, were currently using at least 1 effective method of birth control at the time of Screening and agreed to practice 1 effective method of birth control from Screening through 30 days after stopping study drug. Sexually active males were surgically sterile or, if sexually active with a female partner of childbearing potential, agreed to practice 1 effective form of birth control from Screening through 30 days after stopping study drug. * Screening central laboratory result indicating HCV GT-2 infection without co-infection of any other genotype. * Participant has positive anti-HCV antibody (Ab) and plasma HCV RNA viral load greater than or equal to 1000 IU/mL at Screening Visit. * Chronic HCV infection defined as one of the following: * Positive for anti-HCV Ab and/or HCV RNA at least 6 months before Screening; or * A liver biopsy consistent with chronic HCV infection. * Participant must be HCV treatment-naïve (i.e., patient has not received a single dose of any approved or investigational DAA) and non-cirrhotic. Prior HCV treatment using IFNs with or without ribavirin is acceptable. Previous HCV Interferon (IFN) based treatment must have been completed greater than or equal to 2 months prior to screening.
Exclusion criteria
* Females who were pregnant or planned to become pregnant, or breastfeeding or males whose partner was 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). * Requirement for and inability to safely discontinue contraindicated medications or supplements at least 2 weeks or 10 half-lives (whichever is longer) prior to the first dose of any study drug. * Clinically significant abnormalities, other than HCV-infection, based upon the results of a medical history, physical examination, vital signs, laboratory profile, and a 12-lead electrocardiogram (ECG) that make the participant an unsuitable candidate for this study in the opinion of the investigator, including, but not limited to: * Uncontrolled diabetes as defined by a glycated hemoglobin (hemoglobin A1C) level \> 8.5% at the Screening Visit. * Active or suspected malignancy or history of malignancy (other than basal cell skin cancer or cervical carcinoma in situ) in the past 5 years, or any history of hepatocellular carcinoma (HCC). * Uncontrolled cardiac, respiratory, gastrointestinal, hematologic, neurologic, psychiatric, or other medical disease or disorder, which is unrelated to the existing HCV infection. * Any cause of liver disease other than chronic HCV-infection, including but not limited to the following: * Hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease, autoimmune hepatitis, alcoholic liver disease, or steatohepatitis considered to be the primary cause of the liver disease rather than concomitant/incidental with HCV infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Non-inferiority of Arm A to Arm B | 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 non-inferiority of the ABT-493/ABT-530 8-week regimen (Arm A) to the sofosbuvir and ribavirin 12 week regimen (Arm B) in SVR12 using a non-inferiority margin of 10% in the intent-to-treat (ITT) population. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants in Arm A 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. |
| Percentage of Participants With With On-treatment Virologic Failure | Treatment Weeks 1, 2, 4, 8 (end of treatment for arm A), and 12 (end of treatment for arm B) 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. 95% CI was calculated using the Wilson score method. |
| 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 participants who were been shown to be re-infected. 95% CI was calculated using the Wilson score method. |
Participant flow
Pre-assignment details
Intent-to-treat population: all participants who received at least 1 dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Arm A Co-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis. | 90 |
| Arm B sofosbuvir (400 mg) QD co-administered with weight based ribavirin (RBV) 600-1000 mg divided twice daily (BID) for 12 weeks in HCV GT2 -infected, DAA treatment-naïve participants without cirrhosis. | 46 |
| Total | 136 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Total |
|---|---|---|---|
| Age, Continuous | 57.46 years STANDARD_DEVIATION 13.07 | 58.89 years STANDARD_DEVIATION 13.64 | 57.94 years STANDARD_DEVIATION 13.23 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 90 Participants | 46 Participants | 136 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Female | 48 Participants | 25 Participants | 73 Participants |
| Sex: Female, Male Male | 42 Participants | 21 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 90 | 0 / 46 |
| other Total, other adverse events | 20 / 90 | 26 / 46 |
| serious Total, serious adverse events | 2 / 90 | 2 / 46 |
Outcome results
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Non-inferiority of Arm A to Arm B
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 non-inferiority of the ABT-493/ABT-530 8-week regimen (Arm A) to the sofosbuvir and ribavirin 12 week regimen (Arm B) in SVR12 using a non-inferiority margin of 10% in the intent-to-treat (ITT) population.
Time frame: 12 weeks after the last actual dose of study drug
Population: Intent-to-treat (ITT) 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): Non-inferiority of Arm A to Arm B | 97.8 percentage of participants |
| Arm B | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Non-inferiority of Arm A to Arm B | 93.5 percentage of participants |
Comparison: Difference in SVR12 rates (Arm A - Arm B)95% CI: [-3.5, 12.1]
Secondary
Percentage of Participants in Arm A 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: 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 in Arm A With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 97.8 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 participants who were been shown to be re-infected. 95% CI was calculated using the Wilson score method.
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 (ITT population).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants With Post-Treatment Relapse | 0 percentage of participants |
| Arm B | Percentage of Participants With Post-Treatment Relapse | 4.4 percentage of participants |
Secondary
Percentage of Participants With 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. 95% CI was calculated using the Wilson score method.
Time frame: Treatment Weeks 1, 2, 4, 8 (end of treatment for arm A), and 12 (end of treatment for arm B) 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 With On-treatment Virologic Failure | 0 percentage of participants |
| Arm B | Percentage of Participants With With On-treatment Virologic Failure | 0 percentage of participants |