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

Chronic Hepatitis C Clinical Trial

— TURQUOISE-I  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01939197
• Other study ID #: M14-004
• Secondary ID: 2012-005143-24
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: August 30, 2013
• Est. completion date: October 25, 2016

Study information

• Verified date: July 2021
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 318
• Est. completion date: October 25, 2016
• Est. primary completion date: July 21, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Chronic Hepatitis C
• Coinfection
• Communicable Diseases
• Compensated Cirrhosis and Non-cirrhotics
• Fibrosis
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus Infection
• Hepatitis C, Chronic
• Hepatitis, Chronic
• HIV Infections
• Human Immunodeficiency Virus Infection
• Immunologic Deficiency Syndromes
• Infection
• Virus Diseases

Intervention

Drug:
• ABT-450/r/ABT-267
tablet
• ABT-333
tablet
• ribavirin
tablet

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)

External Links

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