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)

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-Label, Sequential Arm, Multicenter Study to Evaluate the Antiviral Activity, Safety and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) Dosed in Combination With ABT-267 With and Without Ribavirin (RBV) in Treatment-Naïve Subjects With Genotype 1, 2 or 3 Chronic Hepatitis C Virus (HCV) Infection

Conditions
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Hepatitis C Virus

Intervention / Treatment
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* Drug: ABT-450
* Drug: ABT-267
* Drug: ribavirin
* Drug: ritonavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABT-450/r and ABT-267 plus RBV in genotype 1 participants<br>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. | Drug: ABT-450<br>* tablets<br>* Other names: paritaprevir;Drug: ABT-267<br>* tablets<br>* Other names: ombitasvir;Drug: ribavirin<br>* tablets<br>Drug: ritonavir<br>* capsules<br>* Other names: Norvir;|
| Experimental: ABT-450/r and ABT-267 plus RBV in genotype 2 participants<br>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. | Drug: ABT-450<br>* tablets<br>* Other names: paritaprevir;Drug: ABT-267<br>* tablets<br>* Other names: ombitasvir;Drug: ribavirin<br>* tablets<br>Drug: ritonavir<br>* capsules<br>* Other names: Norvir;|
| Experimental: ABT-450/r and ABT-267 plus RBV in genotype 3 participants<br>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. | Drug: ABT-450<br>* tablets<br>* Other names: paritaprevir;Drug: ABT-267<br>* tablets<br>* Other names: ombitasvir;Drug: ribavirin<br>* tablets<br>Drug: ritonavir<br>* capsules<br>* Other names: Norvir;|
| Experimental: ABT-450/r and ABT-267 in genotype 1 participants<br>ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 1 infection. | Drug: ABT-450<br>* tablets<br>* Other names: paritaprevir;Drug: ABT-267<br>* tablets<br>* Other names: ombitasvir;Drug: ritonavir<br>* capsules<br>* Other names: Norvir;|
| Experimental: ABT-450/r and ABT-267 in genotype 2 participants<br>ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 2 infection. | Drug: ABT-450<br>* tablets<br>* Other names: paritaprevir;Drug: ABT-267<br>* tablets<br>* Other names: ombitasvir;Drug: ritonavir<br>* capsules<br>* Other names: Norvir;|
| Experimental: ABT-450/r and ABT-267 in genotype 3 participants<br>ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 3 infection. | Drug: ABT-450<br>* tablets<br>* Other names: paritaprevir;Drug: ABT-267<br>* tablets<br>* Other names: ombitasvir;Drug: ritonavir<br>* capsules<br>* Other names: Norvir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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)] | 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. | Week 4 through Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks (SVR12) Post-treatment | 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. | Post-treatment Day 1 to Post-treatment Week 12 | 
| Percentage of Participants With Sustained Virologic Response 24 Weeks (SVR24) Post-Treatment | 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. | Post-treatment Day 1 to Post-treatment Week 24 | 
| Percentage of Participants With Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) < 1000 International Units Per Milliliter (IU/mL) | Analysis of participants with HCV RNA levels below 1000 IU/mL at Week 2. Participants with missing data were imputed as failures. | Week 2 | 
| 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) | 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. | Week 4 | 
| Percentage of Participants With Virologic Failure During Treatment | 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). | Day 1 through Week 12 | 
| Percentage of Participants Who Experienced Virologic Relapse Through End of Post Treatment Period (up to 48 Weeks) | 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. | Post-treatment Day 1 to Post-treatment Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABT-450/r, Genotype 1, Genotype 2, Genotype 3, Hepatitis C Virus, Ribavirin, ABT-267, Ombitasvir, Paritaprevir