A Study to Evaluate ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Japanese Adults With Chronic Hepatitis C Virus Infection

Study Overview
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Brief Summary
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This study evaluated the safety, tolerability, antiviral activity, and pharmacokinetics of ABT-450 (also known as paritaprevir) with ritonavir (ABT-450/r) and ABT-267 (also known as ombitasvir) in adult Japanese patients with chronic hepatitis C virus genotype 1b (HCV GT1b) or genotype 2 (HCV GT2) infection who were previous treated with pegylated interferon/ribavirin (pegIFN/RBV).

Detailed Description
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This multicenter, randomized, open-label, parallel-arm, combination treatment study consisted of a Treatment and Post-treatment Phase, divided into 2 cohorts: 1) chronic HCV GT1b- infected, pegIFN/RBV treatment-exposed Japanese adults; and 2) HCV GT2-infected, pegIFN/RBV treatment-exposed Japanese adults. The Treatment Phase evaluated the antiviral activity, safety, and pharmacokinetics of a range of ABT-450/r and ABT-267 doses for 12 to 24 weeks. The Post-treatment Phase evaluated the evolution and persistence of viral resistance to ABT-267 and ABT-450.

Official Title
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A Phase 2 Study to Evaluate the Safety, Tolerability, Antiviral Activity, and Pharmacokinetics of ABT-450 With Ritonavir (ABT-450/r) and ABT-267 in Japanese Adults With Chronic Hepatitis C Virus Infection

Conditions
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Chronic Hepatitis C Infection

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


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 post-menopausal for more than 2 years or surgically sterile Chronic hepatitis C, genotype 1b (HCV-GT1b) or genotype 2 (HCV GT2) infection (HCV RNA level greater than 10,000 IU/mL at screening) previously treated with pegylated interferon/ribavirin (pegIFN/RBV). Subject's hepatitis C virus genotype is subgenotype 1b and subject was a null responder or partial responder, OR Subject's hepatitis C virus genotype is subgenotype 2 and subject was a null responder, partial responder, or relapser (Null responder: received at least 10 weeks of pegIFN/RBV for the treatment of HCV and failed to achieve a 2 log10 IU/mL reduction in HCV RNA at Week 12; Partial responders: received at least 20 weeks of pegIFN/RBV for the treatment of HCV and achieved ≥ 2 log10 IU/mL reduction in HCV RNA at Week 12, but failed to achieve HCV RNA undetectable (HCV RNA < lower limit of detection [< LLOD]) at the end of treatment; Relapsers: received at least 1 course of pegIFN/RBV for the treatment of HCV and was undetectable at the end of treatment, but HCV RNA was detectable within 24 weeks of treatment follow-up). Exclusion Criteria: Significant liver disease with any cause other than HCV as the primary cause Positive screen for drugs or alcohol. Positive hepatitis B surface antigen or anti-human immunodeficiency virus antibody. Use of contraindicated medications within 2 weeks of dosing Previous use of any investigational or commercially available anti-Hepatitis C virus agent other than pegIFN/RBV, including previous exposure to ABT-450 or ABT-267.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 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: Arm 1<br>Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. | Drug: ABT-450/ritonavir, ABT-267<br>* ABT-450 (tablet) dosed with ritonavir (capsule), and ABT-267 (tablet)<br>* Other names: ABT/450/r/ABT-267 (ABT-450 coformulated with ritonavir and ABT-267) also known as VIEKIRAX Combination Tablets;|
| Experimental: Arm 2<br>Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. | Drug: ABT-450/ritonavir, ABT-267<br>* ABT-450 (tablet) dosed with ritonavir (capsule), and ABT-267 (tablet)<br>* Other names: ABT/450/r/ABT-267 (ABT-450 coformulated with ritonavir and ABT-267) also known as VIEKIRAX Combination Tablets;|
| Experimental: Arm 3<br>Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 24 weeks. | Drug: ABT-450/ritonavir, ABT-267<br>* ABT-450 (tablet) dosed with ritonavir (capsule), and ABT-267 (tablet)<br>* Other names: ABT/450/r/ABT-267 (ABT-450 coformulated with ritonavir and ABT-267) also known as VIEKIRAX Combination Tablets;|
| Experimental: Arm 4<br>Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 24 weeks. | Drug: ABT-450/ritonavir, ABT-267<br>* ABT-450 (tablet) dosed with ritonavir (capsule), and ABT-267 (tablet)<br>* Other names: ABT/450/r/ABT-267 (ABT-450 coformulated with ritonavir and ABT-267) also known as VIEKIRAX Combination Tablets;|
| Experimental: Arm 5<br>Participants with HCV GT2 received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. | Drug: ABT-450/ritonavir, ABT-267<br>* ABT-450 (tablet) dosed with ritonavir (capsule), and ABT-267 (tablet)<br>* Other names: ABT/450/r/ABT-267 (ABT-450 coformulated with ritonavir and ABT-267) also known as VIEKIRAX Combination Tablets;|
| Experimental: Arm 6<br>Participants with HCV GT2 received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. | Drug: ABT-450/ritonavir, ABT-267<br>* ABT-450 (tablet) dosed with ritonavir (capsule), and ABT-267 (tablet)<br>* Other names: ABT/450/r/ABT-267 (ABT-450 coformulated with ritonavir and ABT-267) also known as VIEKIRAX Combination Tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 24 Weeks After Treatment (SVR24) | The percentage of participants with SVR24 (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). The LLOQ for the assay was 25 IU/mL. | 24 weeks after last dose of study drug | 
| Number of Participants With Adverse Events (AEs) | An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious adverse event (SAE) is an AE that results in death, is life-threatening, results in or prolongs hospitalization, results in congenital anomaly, persistent or significant disability/incapacity, spontaneous or elective abortion, or requires intervention to prevent a serious outcome. AEs were rated for severity as either Mild: transient and easily tolerated; Moderate: causes discomfort and interrupts usual activities; or Severe: causes considerable interference with usual activities, may be incapacitating or life-threatening. AEs related to study drug were assessed as being either probably or possibly related by the investigator. Treatment-emergent AEs (TEAEs) were collected from the first dose of study drug administration to 30 days after last dose; SAEs were collected from the time that informed consent was obtained to 30 days after last dose. | TEAEs: up to 16 weeks for the 12-week treatment groups and up to 28 weeks for the 24-week treatment groups; SAEs: up to 65 weeks for the 12-week treatment groups and up to 77 weeks for the 24-week treatment groups. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks After Treatment (SVR12) | The percentage of participants with SVR12 (plasma HCV RNA level < LLOQ 12 weeks after the last dose of study drug). The LLOQ for the assay was 25 IU/mL. | 12 weeks after last dose of study drug | 
| Percentage of Participants With End of Treatment (EOT) Response | The percentage of participants with EOT response (plasma HCV RNA level < LLOQ at week 12 for the 12-week duration arms and Week 24 for the 24-week duration arms12). The LLOQ for the assay was 25 IU/mL. | 12 or 24 weeks after first dose of study drug | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japanese, Hepatitis C, Genotype 2, Genotype 1b, paritaprevir, ombitasvir, ritonavir, VIEKIRAX Combination Tablets