A Study to Evaluate the Safety and Effect of Co-administration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of co-administration of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adults with chronic hepatitis C virus infection.

Detailed Description
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This was a Phase 2, randomized, open-label, combination treatment study of the 2-DAA regimen (ABT-450 150 mg QD + ritonavir 100 mg QD + ABT-267 25 mg QD) in adult HCV GT1b-infected treatment-naïve and Pegylated-interferon/ribavirin (pegIFN/RBV) treatment-experienced participants without cirrhosis and with compensated cirrhosis, and in adult GT4-infected treatment-naïve and pegIFN/RBV treatment-experienced participants without cirrhosis. Treatment Group 5 was not open to enrollment, based on a protocol-specified interim review of results from the treatment-naïve GT4 Groups 1 and 4 that indicated higher sustained virologic response (SVR) rates among participants receiving the 2-DAA regimen with RBV. All other groups completed the study.

Official Title
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A Randomized, Open-Label Study to Evaluate the Safety and Efficacy of Coadministration of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Adults With Chronic Hepatitis C Virus Infection (PEARL-I)

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: ABT-450/r
* Drug: ABT-267
* Drug: Ribavirin (RBV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females must be practicing specific forms of birth control on study treatment, or be postmenopausal for more than 2 years or surgically sterile Subjects must meet one of the following: Treatment-naive: Subject has never received antiviral treatment for hepatitis C infection OR Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegIFN/RBV); Body mass index (BMI) is ≥ 18 to < 38 kg/m^2. Chronic HCV genotype 1b infection/with or without cirrhosis or HCV genotype 4 infection/without cirrhosis for at least 6 months prior to study screening. Subject has plasma HCV RNA level > 10,000 IU/mL at Screening Exclusion Criteria: History of severe, life-threatening or other significant sensitivity to any drug. Females who were pregnant or planned to become pregnant, or breastfeeding, or GT4-infected males whose partners were pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of study drug/RBV. Recent history of drug or alcohol abuse that could preclude adherence to the protocol. Positive test result for hepatitis B surface antigen or anti-Human Immunodeficiency Virus (HIV) antibodies.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Group 1<br>ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants | Drug: ABT-450/r<br>* Tablet; ABT-450; Capsule; ritonavir<br>* Other names: ABT-450 also known as paritaprevir;Drug: ABT-267<br>* Tablet<br>* Other names: ABT-267 also known as ombitasvir;|
| Experimental: Group 2<br>ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants | Drug: ABT-450/r<br>* Tablet; ABT-450; Capsule; ritonavir<br>* Other names: ABT-450 also known as paritaprevir;Drug: ABT-267<br>* Tablet<br>* Other names: ABT-267 also known as ombitasvir;|
| Experimental: Group 3<br>ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants | Drug: ABT-450/r<br>* Tablet; ABT-450; Capsule; ritonavir<br>* Other names: ABT-450 also known as paritaprevir;Drug: ABT-267<br>* Tablet<br>* Other names: ABT-267 also known as ombitasvir;|
| Experimental: Group 4<br>ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants | Drug: ABT-450/r<br>* Tablet; ABT-450; Capsule; ritonavir<br>* Other names: ABT-450 also known as paritaprevir;Drug: ABT-267<br>* Tablet<br>* Other names: ABT-267 also known as ombitasvir;Drug: Ribavirin (RBV)<br>* Tablet<br>|
| Experimental: Group 5<br>ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-experienced, HCV GT4-infected participants | Drug: ABT-450/r<br>* Tablet; ABT-450; Capsule; ritonavir<br>* Other names: ABT-450 also known as paritaprevir;Drug: ABT-267<br>* Tablet<br>* Other names: ABT-267 also known as ombitasvir;|
| Experimental: Group 6<br>ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if < 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants | Drug: ABT-450/r<br>* Tablet; ABT-450; Capsule; ritonavir<br>* Other names: ABT-450 also known as paritaprevir;Drug: ABT-267<br>* Tablet<br>* Other names: ABT-267 also known as ombitasvir;Drug: Ribavirin (RBV)<br>* Tablet<br>|
| Experimental: Group 7<br>ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis | Drug: ABT-450/r<br>* Tablet; ABT-450; Capsule; ritonavir<br>* Other names: ABT-450 also known as paritaprevir;Drug: ABT-267<br>* Tablet<br>* Other names: ABT-267 also known as ombitasvir;|
| Experimental: Group 8<br>ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis | Drug: ABT-450/r<br>* Tablet; ABT-450; Capsule; ritonavir<br>* Other names: ABT-450 also known as paritaprevir;Drug: ABT-267<br>* Tablet<br>* Other names: ABT-267 also known as ombitasvir;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Each Treatment Group With Sustained Virologic Response 12 Weeks Post-treatment | The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [<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 Each Treatment Group With Sustained Virologic Response 24 Weeks Post-treatment | The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid [HCV RNA] level less than the lower limit of quantitation [<LLOQ]) 24 weeks after the last dose of study drug. | 24 weeks after the last actual dose of study drug | 
| Percentage of Participants in Each Treatment Group With On-treatment Virologic Failure. | Virologic failure during treatment was defined as rebound (confirmed HCV RNA greater than or equal to the lower limit of quantitation [≥ LLOQ] after HCV RNA < LLOQ during treatment, or confirmed increase from the lowest value post baseline in HCV RNA [2 consecutive HCV RNA measurements > 1 log(subscript)10(subscript) IU/mL above the lowest value post baseline] at any time point during treatment), or fail to suppress (HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks [≥ 36 days] of treatment). | Baseline (Day 1), Day 3, and Treatment Weeks 1, 2 ,3 ,4, 6, 8, 10, and 12 for all participants and Treatment Weeks 16, 20 and 24 for Groups 7 and 8 | 
| Percentage of Participants in Each Treatment Group With Post-treatment Virologic Relapse. | Participants were considered to have virologic relapse after treatment if they had confirmed quantifiable plasma Hepatitis C virus ribonucleic acid (HCV RNA) ≥ lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA < LLOQ at the end of treatment. | Within 12 weeks after the last dose of study drug | 
| Percentage of Participants in Each Treatment Group With Treatment-emergent Adverse Events | Treatment-emergent adverse events were defined as any event that began or worsened in severity after initiation of study drug through 30 days after the last dose of study drug. | From the start of study drug administration until 30 days after the last dose,16 weeks for Groups 1, 2, 3, 4, and 6, and 28 weeks for Groups 7 and 8. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C Virus, Ribavirin-Free, Hepatitis C Genotype 1, Hepatitis C, Interferon-Free, Chronic Hepatitis C, Compensated cirrhosis, Hepatitis C Genotype 4, Paritaprevir, Ombitasvir, Ritonavir, Ribavirin