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)
Overview
- Phase
- Phase 3
- Intervention
- ABT-493/ABT-530
- Conditions
- Chronic Hepatitis C Virus
- Sponsor
- AbbVie
- Enrollment
- 295
- Primary Endpoint
- Percentage of Participants in Arms A and B With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
- Status
- Completed
- Last Updated
- 4 years ago
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 \[GT1- or GT2-infected subjects with compensated cirrhosis, HCV GT3-, 4-, 5- and 6-infected subjects (with compensated cirrhosis or without cirrhosis), HCV GT1- and GT2-infected subjects who had failed prior DAA treatments (with compensated cirrhosis or without cirrhosis), HCV GT1- or GT2-infected subjects with severe renal impairment (with compensated cirrhosis or without cirrhosis)\].
Investigators
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.
Arms & Interventions
Arm A
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.
Intervention: ABT-493/ABT-530
Arm B
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.
Intervention: OBV/PTV/r
Arm C
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.
Intervention: ABT-493/ABT-530
Arm D
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.
Intervention: ABT-493/ABT-530
Outcomes
Primary Outcomes
Percentage of Participants in Arms A and B With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
Time Frame: 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 Outcomes
- 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)
- Percentage of Participants With Post-Treatment Relapse(From the end of treatment through 12 weeks after the last 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)(12 weeks after the last actual 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)