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

Study Overview
=================
Brief Summary
-----------------
The purpose of this phase 3, multicenter study is to evaluate the efficacy and safety of ABT-493/ABT-530 in Japanese adults with chronic Hepatitis C Virus (HCV)-infected, HCV direct-acting antiviral agent (DAA) treatment-naïve, and DAA treatment-experienced Japanese adult subjects.

Detailed Description
-----------------
The study consisted of two sub-studies that enrolled in parallel. Substudy 1 was randomized, open-label, and active-controlled, wherein HCV treatment-naïve or interferon (IFN)-experienced (i.e., DAA treatment-naïve), genotype (GT)1-infected participants without cirrhosis were enrolled. Substudy 2 was non-randomized, open label, and enrolled special populations of HCV-infected participants [GT1- or GT2-infected subjects with compensated cirrhosis, HCV GT3-, 4-, 5- and 6-infected subjects (with compensated cirrhosis or without cirrhosis), HCV GT1- and GT2-infected subjects who had failed prior DAA treatments (with compensated cirrhosis or without cirrhosis), HCV GT1- or GT2-infected subjects with severe renal impairment (with compensated cirrhosis or without cirrhosis)].

Official Title
-----------------
A Randomized, Open-Label, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Chronic Hepatitis C Virus Infection (CERTAIN-1)

Conditions
-----------------
Chronic Hepatitis C Virus, Hepatitis C Virus

Intervention / Treatment
-----------------
* Drug: ABT-493/ABT-530
* Drug: OBV/PTV/r


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Females were postmenopausal for at least 2 years; 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 indicated HCV single genotype infection for the appropriate treatment arm, without co-infection of any other genotype. Chronic HCV infection is defined as one of the following: Positive for anti-HCV antibody (Ab) and/or HCV RNA at least 6 months before Screening. A liver biopsy consistent with chronic HCV infection. Agreed to voluntarily sign and date an informed consent form, approved by an Institutional Review Board (IRB)/Independent Ethics Committee (IEC) prior to the initiation of any screening or study specific procedures. Participants who were able to understand and adhere to the study visit schedule and all other protocol requirements. Absence of hepatocellular carcinoma (HCC) as indicated by an ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI). 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. Participants co-infected with hepatitis B virus or human immunodeficiency virus. Use of contraindicated medications or supplements within 2 weeks or 10 half-lives (if known), whichever was longer, prior to the first dose of any study drug. 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. Any cause of liver disease other than chronic HCV infection. Any current or past clinical evidence of Child-Pugh B or C classification or clinical history of decompensated liver disease. Consideration by the investigator, for any reason, that the participant is an unsuitable candidate to receive ABT-493/ABT-530.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

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>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) once daily (QD) for 8 weeks in HCV genotype(GT)1 -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>Ombitasvir (25 mg)/paritaprevir (150 mg)/ritonavir (100mg) (OBV/PTV/r) QD for 12 weeks in HCV GT1 infected, DAA treatment-naïve participants without cirrhosis. | Drug: OBV/PTV/r<br>* Co-formulated tablet<br>* Other names: norvir (ritonavir);|
| Experimental: Arm C<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120mg) QD for 12 weeks in HCV GT1- or GT2-infected participants with compensated cirrhosis, HCV GT3-, 4-, 5- and 6-infected participants (with compensated cirrhosis or without cirrhosis), HCV GT1- and GT2-infected participants who had failed prior DAA treatments (with compensated cirrhosis or without cirrhosis), and HCV GT1- or GT2-infected participants with severe renal impairment and compensated cirrhosis. | Drug: ABT-493/ABT-530<br>* Co-formulated tablet<br>* Other names: pibrentasvir (ABT-530);|
| Experimental: Arm D<br>ABT-493 (300 mg) once daily (QD) co-administered with ABT-530 (120 mg) QD for 8 weeks in GT1- or GT2-infected participants with severe renal impairment and without cirrhosis. | Drug: ABT-493/ABT-530<br>* Co-formulated tablet<br>* Other names: pibrentasvir (ABT-530);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Arms A and B 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 | 

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. 95% CI was calculated using the normal approximation to the binomial distribution. | 12 weeks after the last actual dose of study drug | 
| Percentage of Participants for Each Sub-Population in Arms C and D 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. Subpopulations defined as Genotype 1 and 2 infected cirrhotic participants, prior direct acting antiviral agent (DAA) treatment experienced (T-exp) participants, Genotype 3, 4, 5 or 6-infected participants, and participants with severe renal impairment (RI). 95% CI was calculated using the Wilson score method. | 12 weeks after the last actual dose of study drug | 
| 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. 95% CI was calculated using the Wilson score method. | 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 | 
| 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 participants who were been shown to be re-infected. The confidence interval 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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Compensated cirrhosis, Non-cirrhotic, Renal impairment, Hepatitis C virus (HCV), Hepatitis C, Chronic Hepatitis C, Hepatitis C Genotype 1, Hepatitis C Genotype 2, Hepatitis C Genotype 3, Hepatitis C Genotype 4, Hepatitis C Genotype 5, Hepatitis C Genotype 6, DAA-experienced