A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Genotype 2 Chronic Hepatitis C Virus Infection

Study Overview
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Brief Summary
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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
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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).

Official Title
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A Randomized, Open-Label, Active Comparator, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Genotype 2 Chronic Hepatitis C Virus Infection (CERTAIN-2)

Conditions
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Chronic Hepatitis C Virus, Hepatitis C Virus

Intervention / Treatment
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* Drug: ABT-493/ABT-530
* Drug: sofosbuvir (SOF)
* Drug: ribavirin (RBV)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>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. | Drug: ABT-493/ABT-530<br>* Co-formulated tablet<br>* Other names: pibrentasvir (ABT-530);|
| Active Comparator: Arm B<br>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. | Drug: sofosbuvir (SOF)<br>* Tablet<br>Drug: ribavirin (RBV)<br>* Capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weeks after the last actual dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 12 weeks after the last actual dose of study drug | 
| 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. | 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 | 
| 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. | From the end of treatment through 12 weeks after the last dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis C Virus, Hepatitis C Virus, Non-cirrhotic, Hepatitis C Genotype 2, Hepatitis C