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)

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ClinicalTrials.gov Identifier: NCT01939197

Recruitment Status : Completed

First Posted : September 11, 2013

Results First Posted : November 17, 2017

Last Update Posted : November 17, 2017

Sponsor:

Information provided by (Responsible Party):

AbbVie

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Hepatitis C Virus Infection Human Immunodeficiency Virus Infection Chronic Hepatitis C Compensated Cirrhosis and Non-cirrhotics	Drug: ABT-450/r/ABT-267 Drug: ABT-333 Drug: ribavirin	Phase 2 Phase 3

Study Design


Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	318 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	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)
Study Start Date :	August 30, 2013
Actual Primary Completion Date :	July 21, 2016
Actual Study Completion Date :	October 25, 2016

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: North American Indian childhood cirrhosis

MedlinePlus related topics: HIV/AIDS Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Dasabuvir

U.S. FDA Resources

Arms and Interventions

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: ABT-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir Drug: ribavirin tablet
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: ABT-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir Drug: ribavirin tablet
Experimental: ARM C 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 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir Drug: ribavirin tablet
Experimental: ARM D 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 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir Drug: ribavirin tablet
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-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir
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-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir
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: ABT-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir Drug: ribavirin tablet
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: ABT-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir Drug: ribavirin tablet
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: ABT-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir Drug: ribavirin tablet
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: ABT-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ABT-333 tablet Other Name: Dasabuvir Drug: ribavirin tablet
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: ABT-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ribavirin tablet
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: ABT-450/r/ABT-267 tablet Other Names: ombitasvir/paritaprevir/ritonavir ombitasvir also known as ABT-267 paritaprevir also known as ABT-450 Drug: ribavirin tablet

Outcome Measures

Primary Outcome Measures :

Percentage of Participants in GT1 Analysis Group 1 in Part 2 Achieving Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) [ Time Frame: 12 weeks after the last actual dose of study drug ]
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%).

Secondary Outcome Measures :

Percentage of Participants in Part 1a Achieving SVR12 [ Time Frame: 12 weeks after last dose of study drug ]
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.
Percentage of Participants in Part 1b Achieving SVR12 [ Time Frame: 12 weeks after last dose of study drug ]
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.
Percentage of Participants in Arm F and Arm G of Part 2 Achieving SVR12 [ Time Frame: 12 weeks after last dose of study drug ]
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.
Percentage of Participants With GT4 HCV in Part 2 Achieving SVR12, by Arm and Overall [ Time Frame: 12 weeks after last dose of study drug ]
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.
Percentage of Participants in Part 1a With On-Treatment HCV Virologic Failure During the Treatment Period [ Time Frame: up to 12 or 24 weeks, based on treatment duration ]
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.
Percentage of Participants in Part 1b With On-Treatment HCV Virologic Failure During the Treatment Period [ Time Frame: up to 12 weeks ]
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.
Percentage of Participants in Part 2 With On-Treatment HCV Virologic Failure During the Treatment Period [ Time Frame: up to 12 or 24 weeks, based on treatment duration ]
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.
Percentage of Participants in Part 1a With Relapse12 [ Time Frame: up to 12 or 24 weeks, based on treatment duration, after the last actual dose of study drug ]
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.
Percentage of Participants in Part 1b With Relapse12 for Each Arm and Overall [ Time Frame: up to 12 weeks after the last actual dose of study drug ]
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.
Percentage of Participants in Part 2 With Relapse12 [ Time Frame: up to 12 or 24 weeks, based on treatment duration, after the last actual dose of study drug ]
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.
Percentage of Participants in Part 1a With Plasma HIV-1 RNA Suppression at End of Treatment and 12 Weeks Post-Treatment [ Time Frame: 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) ]
HIV virologic success was defined as HIV-1 RNA suppression (HIV-1 RNA value < 40 copies/mL).
Percentage of Participants in Part 1b With Plasma HIV-1 RNA Suppression at End of Treatment and 12 Weeks Post-Treatment [ Time Frame: End of treatment: HIV Week 12 window (Treatment Day 78 - 98). PTW12: HIV PTW12 window (Post-Treatment Day 57 - 126) ]
HIV virologic success was defined as HIV-1 RNA suppression (HIV-1 RNA value < 40 copies/mL).
Percentage of Participants in Part 2 With Plasma HIV-1 RNA Suppression at End of Treatment and 12 Weeks Post-Treatment [ Time Frame: 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) ]
HIV virologic success was defined as HIV-1 RNA suppression (HIV-1 RNA value < 40 copies/mL).

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	18 Years to 99 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01939197

Sponsors and Collaborators

AbbVie

Investigators


Study Director:	Rolando Viani, MD	AbbVie

More Information

Additional Information:

This clinical study may be evaluating a usage that is not currently FDA-approved. Please see US Prescribing Information for approved uses. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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). pii: e02135-16. doi: 10.1128/AAC.02135-16. Print 2017 Feb.

Saeed S, Strumpf EC, Walmsley SL, Rollet-Kurhajec K, Pick N, Martel-Laferrière V, Hull M, Gill MJ, Cox J, Cooper C, Klein MB; Canadian Co-Infection Cohort Study, Cohen J, Conway B, Cooper C, Côté 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.

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.


Responsible Party:	AbbVie
ClinicalTrials.gov Identifier:	NCT01939197 History of Changes
Other Study ID Numbers:	M14-004 2012-005143-24 ( EudraCT Number )
First Posted:	September 11, 2013 Key Record Dates
Results First Posted:	November 17, 2017
Last Update Posted:	November 17, 2017
Last Verified:	October 2017

Keywords provided by AbbVie:


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

Additional relevant MeSH terms:


Infection Communicable Diseases Hepatitis Hepatitis A Virus Diseases Hepatitis C Hepatitis, Chronic Immunologic Deficiency Syndromes Fibrosis Hepatitis C, Chronic Acquired Immunodeficiency Syndrome HIV Infections Coinfection Liver Cirrhosis Liver Diseases	Digestive System Diseases Hepatitis, Viral, Human Enterovirus Infections Picornaviridae Infections RNA Virus Infections Flaviviridae Infections Immune System Diseases Pathologic Processes Lentivirus Infections Retroviridae Infections Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Slow Virus Diseases Parasitic Diseases Ribavirin

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