Clinical Trials

MainTitle

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)

This study has been completed
Sponsor
AbbVie


Information provided by (Responsible Party)
AbbVie
ClinicalTrials.gov Identifier
NCT01939197

First received: September 6, 2013
Last updated: October 13, 2017
Last Verified: October 2017
History of Changes
Purpose

Purpose

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 Intervention 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 Type: Interventional
Study Design: 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)

Further study details as provided by AbbVie:

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).

Enrollment: 318
Study Start Date: August 30, 2013
Study Completion Date: October 25, 2016
Primary Completion Date: July 21, 2016 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
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 Name:
  • 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 Name:
  • 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 Name:
  • 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 Name:
  • 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 Name:
  • 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 Name:
  • 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 Name:
  • 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 Name:
  • 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 Name:
  • 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 Name:
  • 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 Name:
  • 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 Name:
  • ombitasvir/paritaprevir/ritonavir
  • ombitasvir also known as ABT-267
  • paritaprevir also known as ABT-450

Drug: ribavirin

tablet

Eligibility

Eligibility

Ages Eligible for Study: 18 Years to 99 Years  
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

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01939197

Sponsors and Collaborators

AbbVie

Investigators

Study Director: Rolando Viani, MD AbbVie
More Information

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.

Responsible Party: AbbVie  
ClinicalTrials.gov Identifier: NCT01939197   History of Changes  
Other Study ID Numbers: M14-004  
  2012-005143-24  
Study First Received: September 6, 2013  
Last Updated: October 13, 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
Ribavirin
Ritonavir

ClinicalTrials.gov processed this data on December 08, 2017
This information is provided by ClinicalTrials.gov.