A Study to Evaluate Paritaprevir With Ritonavir (ABT-450/r) When Given Together With Ombitasvir and With and Without Ribavirin (RBV) in Treatment-Naïve Participants With Genotype 1, 2 or 3 Chronic Hepatitis C Virus (HCV)
- Conditions
- Hepatitis C Virus
- Interventions
- Registration Number
- NCT01458535
- Lead Sponsor
- AbbVie (prior sponsor, Abbott)
- Brief Summary
The purpose of this study was to evaluate the efficacy, safety and pharmacokinetics of ABT-450/r when given together with ABT-267 and with and without RBV in treatment-naïve participants with genotype 1, 2 or 3 chronic HCV infection.
- Detailed Description
This was a 2 sequential arm, combination treatment study where each arm contained 3 cohorts: one each for HCV genotype 1, 2, and 3. The study consisted of 2 phases, a treatment phase and a post-treatment phase. The treatment phase was designed to explore the antiviral activity, safety and pharmacokinetics of ABT-450/r dosed in combination with ABT-267 with and without RBV for up to 12 weeks. The post-treatment phase was designed to monitor and evaluate Sustained Virologic Response (SVR) 12, SVR 24, and the evolution and persistence of viral resistance to ABT-267 and ABT-450 in HCV genotype 1-, 2-, and 3-infected participants who have been exposed to ABT-267 and ABT-450/r. Arms 1 and 2 were enrolled sequentially.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 61
- Participants who had a body mass index 18 to < 35 kg/m^2.
- Females were either postmenopausal for at least 2 years, surgically sterile, or willing to use at least 2 effective forms of birth control.
- Males must have been surgically sterile or agreed to use at least 2 effective forms of birth control throughout the course of the study.
- Participants were in a condition of general good health, other than the HCV infection.
- Participants had a chronic HCV genotype 1, 2, or 3 infection for at least 6 months, a plasma HCV RNA > 50,000 IU/mL, and FibroTest score <= 0.72 and aspartate aminotransferase (AST) to platelet ratio index <= 2, Fibroscan® result of < 9.6 kilopascal (kPa), or absence of cirrhosis based on a liver biopsy.
- Positive drug screen
- Previous use of anti-HCV agents
- History of cardiac disease
- History of uncontrolled diabetes or diabetes requiring insulin
- Abnormal laboratory results
- Females who were pregnant or planned to become pregnant within 6 months after their last dose of study drug/RBV or were breastfeeding; males whose partners were pregnant or would become pregnant within 6 months after their last dose of study drug/RBV
- Positive test result for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus (HIV) antibody (Ab). Negative HIV status was to be confirmed at screening.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ABT-450/r and ABT-267 plus RBV in genotype 2 participants ABT-267 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection. ABT-450/r and ABT-267 plus RBV in genotype 1 participants ABT-450 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection. ABT-450/r and ABT-267 plus RBV in genotype 3 participants ABT-450 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection. ABT-450/r and ABT-267 in genotype 1 participants ABT-267 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 1 infection. ABT-450/r and ABT-267 plus RBV in genotype 1 participants ABT-267 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection. ABT-450/r and ABT-267 in genotype 1 participants ABT-450 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 1 infection. ABT-450/r and ABT-267 in genotype 3 participants ABT-267 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 3 infection. ABT-450/r and ABT-267 plus RBV in genotype 2 participants ABT-450 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection. ABT-450/r and ABT-267 plus RBV in genotype 3 participants ABT-267 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection. ABT-450/r and ABT-267 in genotype 2 participants ABT-267 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 2 infection. ABT-450/r and ABT-267 in genotype 3 participants ABT-450 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 3 infection. ABT-450/r and ABT-267 in genotype 2 participants ABT-450 ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 2 infection. ABT-450/r and ABT-267 plus RBV in genotype 1 participants ribavirin ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection. ABT-450/r and ABT-267 plus RBV in genotype 1 participants ritonavir ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection. ABT-450/r and ABT-267 plus RBV in genotype 2 participants ritonavir ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection. ABT-450/r and ABT-267 plus RBV in genotype 2 participants ribavirin ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection. ABT-450/r and ABT-267 plus RBV in genotype 3 participants ribavirin ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection. ABT-450/r and ABT-267 plus RBV in genotype 3 participants ritonavir ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection. ABT-450/r and ABT-267 in genotype 2 participants ritonavir ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 2 infection. ABT-450/r and ABT-267 in genotype 1 participants ritonavir ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 1 infection. ABT-450/r and ABT-267 in genotype 3 participants ritonavir ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 3 infection.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Suppressed Below the Lower Limit of Quantitation (LLOQ) From Week 4 Through Week 12 [(Extended Rapid Virologic Response (eRVR)] Week 4 through Week 12 Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (\< 25 IU/mL). Participants with missing data were imputed as failures.
- Secondary Outcome Measures
Name Time Method Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment Post-treatment Day 1 to Post-treatment Week 24 Sustained Virologic Response 24 (SVR24) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ; \< 25 IU/mL) 24 weeks after the last dose of study drug. Participants with missing data were imputed as failures.
Percentage of Participants Who Experienced Virologic Relapse Through End of Post Treatment Period (up to 48 Weeks) Post-treatment Day 1 to Post-treatment Week 48 Virologic relapse is defined as confirmed hepatitis C virus (HCV) ribonucleic acid (RNA) \>= lower limit of quantitation (LLOQ) (2 consecutive measurements \>= LLOQ) at any point in the post-treatment period among participants with HCV RNA \< LLOQ at the end of treatment. Participants with missing data were imputed as failures.
Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment Post-treatment Day 1 to Post-treatment Week 12 Sustained Virologic Response 12 (SVR12) is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (\< LLOQ; \< 25 IU/mL) 12 weeks after the last dose of study drug. Participants with missing data were imputed as failures.
Percentage of Participants With Virologic Failure During Treatment Day 1 through Week 12 Virologic failure during treatment is defined as a participant meeting any virologic stopping criteria, including 1) rebound (defined as the first day of 2 consecutive increases of at least 0.5 log10 IU/mL above nadir (local minimum value), or first day of 2 consecutive HCV RNA \>= LLOQ for participants who previously achieved HCV RNA \< LLOQ) during treatment, 2) participant who fails to suppress (defined as never achieving HCV RNA \< LLOQ during treatment).
Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) < 1000 International Units Per Milliliter (IU/mL) Week 2 Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2. Participants with missing data were imputed as failures.
Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Below the Lower Limit of Quantitation (LLOQ) at Week 4 Rapid Virologic Response (RVR) Week 4 Analysis of percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (\< 25 IU/mL). Participants with missing data were imputed as failures.