ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 in Treatment-Naïve and Treatment-Experienced, Non-Cirrhotic Asian Adults With Subgenotype 1b Chronic Hepatitis C Virus (HCV) Infection

Study Overview
=================
Brief Summary
-----------------
This is a study to evaluate ABT 450/r/ABT-267 and ABT-333 in treatment-naïve and treatment-experienced Asian adults with subgenotype 1b chronic HCV without cirrhosis.

Official Title
-----------------
A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 in Treatment-Naïve and Treatment-Experienced, Non-Cirrhotic Asian Adults With Subgenotype 1b Chronic Hepatitis C Virus (HCV) Infection

Conditions
-----------------
Hepatitis C Virus (HCV)

Intervention / Treatment
-----------------
* Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir
* Drug: Placebo for ombitasvir/paritaprevir/ritonavir and dasabuvir


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Chinese, South Korean, and Taiwanese descent with full Chinese, South Korean, and Taiwanese parentage Chronic hepatitis C virus (HCV) infection prior to study enrollment. Screening laboratory result indicating HCV subtype 1b (GT1b) infection. Per local standard practice, documented absence of cirrhosis. Participant has never received antiviral treatment (including interferon [IFN]-based therapy [alpha, beta or pegylated (peg)IFN] with or without RBV) for HCV infection (treatment-naïve participant) or participant must have documentation that they met the definition of one of the following categories (treatment experienced participant): Non-responder or Relapser Participant has plasma HCV RNA level > 10,000 IU/mL at Screening. Exclusion Criteria: HCV genotype performed during screening indicating unable to genotype or infection with any HCV genotype other than GT1b. Positive test result at Screening for hepatitis B surface antigen (HBsAg), or hepatitis B virus DNA (HBV-DNA) > Lower Limit of Quantification (LLOQ) if HBsAg negative, or anti-human immunodeficiency virus antibody (HIV Ab) positive. Any current or past clinical evidence of cirrhosis. Any primary cause of liver disease other than chronic HCV infection. Screening laboratory analyses showing abnormal kidney, hepatic, or hematologic function. Use of known strong inducers of cytochrome P450 3A (CYP3A) or strong inhibitors of cytochrome P450 3A (CYP2C8) within 2 weeks or within 10 half-lives, whichever is longer, of the respective medication/supplement prior to study drug administration.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Double-blind 3-DAA<br>Double-blind 3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) for 12 weeks. | Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir<br>* Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet<br>* Other names: dasabuvir also known as ABT-333;|
| Experimental: Double-blind Placebo Followed by Open-label 3-DAA<br>Double-blind placebo for 12 weeks, followed by open-label 3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 mg once daily] and dasabuvir [250 mg twice daily]) for 12 weeks. | Drug: ombitasvir/paritaprevir/ritonavir and dasabuvir<br>* Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet<br>* Other names: dasabuvir also known as ABT-333;Drug: Placebo for ombitasvir/paritaprevir/ritonavir and dasabuvir<br>* Placebo for ombitasvir/paritaprevir/ritonavir and dasabuvir<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 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 active study drug. The primary efficacy endpoint was superiority of the percentage of treatment-naïve and treatment-experienced HCV subgenotype 1b (GT1b)-infected participants treated with 3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 once daily] and dasabuvir [250 mg twice daily]) who achieved SVR12 compared with the historical control rate for comparable patients treated with telaprevir (TVR) plus pegylated interferon (pegIFN) and RBV. | 12 weeks after the last actual dose of active study drug | 
| Percentage of Participants With Sustained Virologic Response 24 Weeks Post-treatment (SVR24) | SVR24 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 active study drug. The primary efficacy endpoint was superiority of the percentage of treatment-naïve and treatment-experienced HCV subgenotype 1b (GT1b)-infected participants treated with 3-DAA (ombitasvir/paritaprevir/ritonavir [25 mg/150 mg/100 once daily] and dasabuvir [250 mg twice daily]) who achieved SVR24 compared with the historical control rate for comparable patients treated with telaprevir (TVR) plus pegylated interferon (pegIFN) and RBV. | 24 weeks after the last actual dose of active study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With On-treatment Virologic Failure | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during active treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during active treatment; or all on-treatment values of HCV RNA ≥ LLOQ with at least 6 weeks of active treatment. | up to 12 weeks | 
| Percentage of Participants With Post-treatment Relapse by Post-treatment Week 12 | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of active study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment. | From the end of treatment through 12 weeks after the last dose of active study drug | 
| Percentage of Participants With Post-treatment Relapse by Post-treatment Week 24 | Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 24 weeks after the last dose of active study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment. | From the end of treatment through 24 weeks after the last dose of active study drug | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HCV Infection, Chronic Hepatitis C Virus, Hepatitis C Virus (HCV) Genotype 1b