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 (TURQUOISE-I)

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)

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection; Chronic Hepatitis C; Human Immunodeficiency Virus Infection; Compensated Cirrhosis and Non-cirrhotics
• Intervention / Treatment: Drug: ribavirin; Drug: ABT-333; Drug: ABT-450/r/ABT-267

• Study Type: Interventional
• Enrollment (Actual): 318
• Phase: Phase 2; Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

12

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ARM A; 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: ribavirin; tablet; Drug: ABT-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM B; 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: ribavirin; tablet; Drug: ABT-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM C; ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for participants receiving darunavir once-daily	Drug: ribavirin; tablet; Drug: ABT-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM D; ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for participants receiving darunavir twice-daily	Drug: ribavirin; tablet; Drug: ABT-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM E; 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-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM F; 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-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM G; 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: ribavirin; tablet; Drug: ABT-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM H; 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: ribavirin; tablet; Drug: ABT-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM I; 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: ribavirin; tablet; Drug: ABT-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM J; 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: ribavirin; tablet; Drug: ABT-333; tablet; Other Names: Dasabuvir; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM K; 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: ribavirin; tablet; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir
Experimental: ARM L; 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: ribavirin; tablet; Drug: ABT-450/r/ABT-267; tablet; Other Names: paritaprevir also known as ABT-450; ombitasvir also known as ABT-267; ombitasvir/paritaprevir/ritonavir

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Rolando Viani, MD, AbbVie

Publications and helpful links

General Publications

• Kwo PY, Poordad F, Asatryan A, Wang S, Wyles DL, Hassanein T, Felizarta F, Sulkowski MS, Gane E, Maliakkal B, Overcash JS, Gordon SC, Muir AJ, Aguilar H, Agarwal K, Dore GJ, Lin CW, Liu R, Lovell SS, Ng TI, Kort J, Mensa FJ. Glecaprevir and pibrentasvir yield high response rates in patients with HCV genotype 1-6 without cirrhosis. J Hepatol. 2017 Aug;67(2):263-271. doi: 10.1016/j.jhep.2017.03.039. Epub 2017 Apr 13.
• Sulkowski MS, Eron JJ, Wyles D, Trinh R, Lalezari J, Wang C, Slim J, Bhatti L, Gathe J, Ruane PJ, Elion R, Bredeek F, Brennan R, Blick G, Khatri A, Gibbons K, Hu YB, Fredrick L, Schnell G, Pilot-Matias T, Tripathi R, Da Silva-Tillmann B, McGovern B, Campbell AL, Podsadecki T. Ombitasvir, paritaprevir co-dosed with ritonavir, dasabuvir, and ribavirin for hepatitis C in patients co-infected with HIV-1: a randomized trial. JAMA. 2015 Mar 24-31;313(12):1223-31. doi: 10.1001/jama.2015.1328.
• King JR, Khatri A, Trinh R, Viani RM, Ding B, Zha J, Menon R. Pharmacokinetic Evaluation of Darunavir Administered Once or Twice Daily in Combination with Ritonavir or the Three-Direct-Acting Antiviral Regimen of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir in Adults Coinfected with Hepatitis C and Human Immunodeficiency Viruses. Antimicrob Agents Chemother. 2017 Jan 24;61(2):e02135-16. doi: 10.1128/AAC.02135-16. Print 2017 Feb.
• Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferriere V, Hull M, Gill MJ, Cox J, Cooper C, Klein MB; Canadian Co-Infection Cohort Study; Cohen J, Conway B, Cooper C, Cote P, Cox J, Gill J, Haider S, Harris M, Haase D, Hull M, Montaner J, Moodie E, Pick N, Rachlis A, Rouleau D, Sandre R, Tyndall JM, Vachon ML, Walmsley S, Wong D. How Generalizable Are the Results From Trials of Direct Antiviral Agents to People Coinfected With HIV/HCV in the Real World? Clin Infect Dis. 2016 Apr 1;62(7):919-926. doi: 10.1093/cid/civ1222. Epub 2016 Jan 6.

Helpful Links

• This clinical study may be evaluating a usage that is not currently FDA-approved. Please see US Prescribing Information for approved uses.

Study record dates

Study Major Dates

• Study Start: August 30, 2013
• Primary Completion (Actual): July 21, 2016
• Study Completion (Actual): October 25, 2016

Study Registration Dates

• First Submitted: September 6, 2013
• First Submitted That Met QC Criteria: September 6, 2013
• First Posted (Estimate): September 11, 2013

Study Record Updates

• Last Update Posted (Actual): July 12, 2021
• Last Update Submitted That Met QC Criteria: July 8, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: HIV-1; Compensated Cirrhosis; Hepatitis C Genotype 1; Hepatitis C; Interferon-Free; Cirrhotic; Hepatitis C Genotype 4; HCV Genotype 4; HCV Genotype 1; HCV / HIV coinfection
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Slow Virus Diseases; Fibrosis; HIV Infections; Infections; Communicable Diseases; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Hepatitis, Chronic; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Hepatitis C, Chronic; Coinfection; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ribavirin; Ritonavir
• Other Study ID Numbers: M14-004; 2012-005143-24 (EudraCT Number)