A Multipart, Open-label Study to Evaluate the Safety and Efficacy of ABT-450/r/ABT-267 With and Without ABT-333 Coadministered With and Without Ribavirin in Adult With Genotype 1 or 4 Hepatitis C Virus (HCV) Infection and Human Immunodeficiency Virus, Type 1 Coinfection

Study Overview
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Brief Summary
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The primary objectives of this study are to assess the safety of ABT-450/r/ABT-267 with and without ABT-333 coadministered with and without ribavirin (RBV) for 12 and 24 weeks in HCV GT1- or 4-infected participants with HIV-1 coinfection and to evaluate the percentage of subjects achieving HCV ribonucleic acid (RNA) < lower limit of quantification (LLOQ) 12 weeks following treatment.

Official Title
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A Multipart, Open-label Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir With and Without Dasabuvir Coadministered With and Without Ribavirin in Adults With Genotype 1 or 4 Chronic Hepatitis C Virus Infection and Human Immunodeficiency Virus, Type 1 Coinfection (TURQUOISE-I)

Conditions
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Hepatitis C Virus Infection, Human Immunodeficiency Virus Infection, Chronic Hepatitis C, Compensated Cirrhosis and Non-cirrhotics

Intervention / Treatment
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* Drug: ABT-450/r/ABT-267
* Drug: ABT-333
* Drug: ribavirin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Chronic HCV infection at screening defined as: positive anti-HCV antibodies (Ab) at screening and HCV RNA > 1,000 IU/mL at screening. Plasma HIV-1 RNA < 40 copies/mL during screening using Abbott RealTime HIV-1 assay. On a stable qualifying HIV-1 antiretroviral therapy regimen. Exclusion Criteria: Positive test result at screening for hepatitis B surface antigen. Evidence of HCV genotype other than genotype 1 or genotype 4 during screening. Receipt of any other investigational or commercially available anti-HCV agents (for example, telaprevir, boceprevir, simeprevir, daclatasvir and ledipasvir) with the exception of interferon (including pegylated-interferon alfa-2a or alfa-2b), sofosbuvir and ribavirin. Consideration by the investigator, for any reason, that the subject is an unsuitable candidate to receive ABT-450, ABT-267, ABT-333, ritonavir or ribavirin. Chronic human immunodeficiency virus, type 2 (HIV-2) infection.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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 A<br>ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks for participants receiving atazanavir once-daily or raltegravir twice-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;Drug: ribavirin<br>* tablet<br>|
| Experimental: ARM B<br>ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 24 weeks for participants receiving atazanavir once-daily or raltegravir twice-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;Drug: ribavirin<br>* tablet<br>|
| Experimental: ARM C<br>ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for participants receiving darunavir once-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;Drug: ribavirin<br>* tablet<br>|
| Experimental: ARM D<br>ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for participants receiving darunavir twice-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;Drug: ribavirin<br>* tablet<br>|
| Experimental: ARM E<br>ABT-450/r/ABT-267 and ABT-333 for 12 weeks for noncirrhotic (at screening) GT1b-infected participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;|
| Experimental: ARM F<br>ABT-450/r/ABT-267 and ABT-333 for 12 weeks for cirrhotic (at screening) GT1b-infected sofosbuvir-naive participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;|
| Experimental: ARM G<br>ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for cirrhotic (at screening) GT1b-infected sofosbuvir-naive participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;Drug: ribavirin<br>* tablet<br>|
| Experimental: ARM H<br>ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for cirrhotic (at screening) GT1b-infected sofosbuvir-experienced participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;Drug: ribavirin<br>* tablet<br>|
| Experimental: ARM I<br>ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for noncirrhotic (at screening) GT1a-infected participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;Drug: ribavirin<br>* tablet<br>|
| Experimental: ARM J<br>ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 24 weeks for cirrhotic (at screening) GT1a-infected participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ABT-333<br>* tablet<br>* Other names: Dasabuvir;Drug: ribavirin<br>* tablet<br>|
| Experimental: ARM K<br>ABT-450/r/ABT-267 coadministered with RBV for 12 weeks for participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily, dolutegravir once-daily or twice-daily, darunavir once-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ribavirin<br>* tablet<br>|
| Experimental: ARM L<br>ABT-450/r/ABT-267 coadministered with RBV for 24 weeks for participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily, dolutegravir once-daily or twice-daily, darunavir once-daily | Drug: ABT-450/r/ABT-267<br>* tablet<br>* Other names: paritaprevir also known as ABT-450;Drug: ribavirin<br>* tablet<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in GT1 Analysis Group 1 in Part 2 Achieving Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) | SVR12 is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (< LLOQ) 12 weeks after the last dose of study drug without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. The 95% confidence interval (CI) is calculated using the Wilson score method for binomial distribution. The primary efficacy endpoint was the non-inferiority of the percentage of participants in the GT1 Analysis Group in Part 2 achieving SVR12 compared to the historical SVR12 rate for sofosbuvir plus ribavirin (a non-inferiority threshold of the lower bound of the 95% CI of 74%). | 12 weeks after the last actual dose of study drug | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants in Part 1a Achieving SVR12 | SVR12 is defined as plasma HCV RNA < LLOQ 12 weeks after the last dose of study drug without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. The 95% CI is calculated using the Wilson score method for binomial distribution. | 12 weeks after last dose of study drug | 
| Percentage of Participants in Part 1b Achieving SVR12 | SVR12 is defined as plasma HCV RNA < LLOQ 12 weeks after the last dose of study drug without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. The 95% CI is calculated using the Wilson score method for binomial distribution. | 12 weeks after last dose of study drug | 
| Percentage of Participants in Arm F and Arm G of Part 2 Achieving SVR12 | SVR12 is defined as plasma HCV RNA < LLOQ 12 weeks after the last dose of study drug without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. The 95% CI is calculated using the Wilson score method for binomial distribution. | 12 weeks after last dose of study drug | 
| Percentage of Participants With GT4 HCV in Part 2 Achieving SVR12, by Arm and Overall | SVR12 is defined as plasma HCV RNA < LLOQ 12 weeks after the last dose of study drug without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. The 95% CI is calculated using the Wilson score method for binomial distribution. | 12 weeks after last dose of study drug | 
| Percentage of Participants in Part 1a With On-Treatment HCV Virologic Failure During the Treatment Period | Percentage of participants with on-treatment HCV virologic failure during the treatment period for each arm in Part 1a. Virologic failure is defined as confirmed quantifiable HCV RNA among participants with previously unquantifiable HCV RNA during treatment. | up to 12 or 24 weeks, based on treatment duration | 
| Percentage of Participants in Part 1b With On-Treatment HCV Virologic Failure During the Treatment Period | Percentage of participants with on-treatment HCV virologic failure during the treatment period for each arm and overall in Part 1b. Virologic failure is defined as confirmed quantifiable HCV RNA among participants with previously unquantifiable HCV RNA during treatment. | up to 12 weeks | 
| Percentage of Participants in Part 2 With On-Treatment HCV Virologic Failure During the Treatment Period | Percentage of participants with on-treatment HCV virologic failure during the treatment period for arms in Part 2. Virologic failure is defined as confirmed quantifiable HCV RNA among participants with previously unquantifiable HCV RNA during treatment. | up to 12 or 24 weeks, based on treatment duration | 
| Percentage of Participants in Part 1a With Relapse12 | Percentage of participants who experienced Relapse12 among participants who completed treatment with HCV RNA < LLOQ at final treatment visit and had at least one post-treatment HCV RNA value. Relapse12 is defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last actual dose of study drug (up to and including the SVR12 assessment time point) for a participant with HCV RNA < LLOQ at final treatment visit who completed treatment and had post-treatment data. Completion of treatment is defined as study drug duration ≥ 77 days for Arm A and ≥ 154 days for Arm B. The 95% CI is calculated using Wilson score method for the binomial distribution. | up to 12 or 24 weeks, based on treatment duration, after the last actual dose of study drug | 
| Percentage of Participants in Part 1b With Relapse12 for Each Arm and Overall | Percentage of participants who experienced Relapse12 among participants who completed treatment with HCV RNA < LLOQ at final treatment visit and had at least one post-treatment HCV RNA value. Relapse12 is defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last actual dose of study drug (up to and including the SVR12 assessment time point) for a participant with HCV RNA < LLOQ at final treatment visit who completed treatment and had post-treatment data. Completion of treatment is defined as study drug duration ≥ 77 days for Arm C and Arm D. The 95% CI is calculated using Wilson score method for the binomial distribution. | up to 12 weeks after the last actual dose of study drug | 
| Percentage of Participants in Part 2 With Relapse12 | Percentage of participants who experienced Relapse12 among those who completed treatment with HCV RNA < LLOQ at final treatment visit and had ≥1 post-treatment HCV RNA value. Relapse12=confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last actual dose of study drug (up to and including the SVR12 window) for a participant with HCV RNA < LLOQ at final treatment visit who completed treatment and had post-treatment data, excluding reinfection. Completion of treatment=study drug duration ≥ 77 days for participants who received 12 weeks of treatment and ≥154 days for participants who received 24 weeks of treatment. HCV reinfection=confirmed HCV RNA ≥ LLOQ after the end of treatment in a subject who had HCV RNA < LLOQ at final treatment visit, along with the post-treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis. The 95% CI is calculated using Wilson score method for the binomial distribution. | up to 12 or 24 weeks, based on treatment duration, after the last actual dose of study drug | 
| Percentage of Participants in Part 1a With Plasma HIV-1 RNA Suppression at End of Treatment and 12 Weeks Post-Treatment | HIV virologic success was defined as HIV-1 RNA suppression (HIV-1 RNA value < 40 copies/mL). | End of treatment: HIV Week 12 window for 12-weeks of treatment (Treatment Day 71 - 98) or HIV Week 24 window (Treatment Day 155 - 182) for 24-weeks of treatment. Post-Treatment Week 12 (PTW12): HIV PTW12 window (Post-Treatment Day 57 - 126) | 
| Percentage of Participants in Part 1b With Plasma HIV-1 RNA Suppression at End of Treatment and 12 Weeks Post-Treatment | HIV virologic success was defined as HIV-1 RNA suppression (HIV-1 RNA value < 40 copies/mL). | End of treatment: HIV Week 12 window (Treatment Day 78 - 98). PTW12: HIV PTW12 window (Post-Treatment Day 57 - 126) | 
| Percentage of Participants in Part 2 With Plasma HIV-1 RNA Suppression at End of Treatment and 12 Weeks Post-Treatment | HIV virologic success was defined as HIV-1 RNA suppression (HIV-1 RNA value < 40 copies/mL). | End of treatment: HIV Week 12 window for 12-weeks of treatment (Treatment Day 71 - 98) or HIV Week 24 window (Treatment Day 155 - 182) for 24-weeks of treatment. PTW12: HIV PTW12 window (Post-Treatment Day 57 - 126) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV Genotype 4, Interferon-Free, Hepatitis C Genotype 1, Compensated Cirrhosis, Hepatitis C Genotype 4, HCV / HIV coinfection, Cirrhotic, Hepatitis C, HIV-1, HCV Genotype 1