A Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With Ribavirin in Adults With Genotype 1 and Ombitasvir/Paritaprevir/Ritonavir With Ribavirin in Adults With Genotype 4 Chronic Hepatitis C Virus Infection and Decompensated Cirrhosis (TURQUOISE-CPB)

An Open-Label Study to Evaluate the Safety and Efficacy of Ombitasvir/Paritaprevir/Ritonavir and Dasabuvir With Ribavirin in Adults With Genotype 1 and Ombitasvir/Paritaprevir/Ritonavir With Ribavirin in Adults With Genotype 4 Chronic Hepatitis C Virus Infection and Decompensated Cirrhosis (TURQUOISE-CPB)

The primary objectives of this study are to assess the safety and the SVR12 rate of ombitasvir/paritaprevir/ritonavir and dasabuvir with RBV in GT1-infected participants with decompensated cirrhosis.

Study Overview

• Status: Completed
• Conditions: Decompensated Cirrhosis; Chronic Hepatitis C; Hepatitis C Virus
• Intervention / Treatment: Drug: ombitasvir/paritaprevir/ritonavir; Drug: dasabuvir; Drug: ribavirin

• Study Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. HCV GT1- or GT4-infection defined as: positive for anti-HCV Ab, HCV RNA > 1,000 IU/mL and laboratory result indicating HCV GT1 or GT4 infection at Screening.
2. Evidence of cirrhosis by prior liver biopsy, FibroScan or by radiograph (i.e., computed tomography [CT] scan or magnetic resonance imaging [MRI]).
3. Child-Pugh Score of 7 - 9, inclusive, at time of Screening.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding.
2. Positive test result for Hepatitis B surface antigen (HbsAg) or anti-HIV antibodies (HIV Ab).
3. Prior or current use of any other investigational or commercially available anti-HCV agents other than interferon/RBV and/or pegylated interferon (pegIFN)/RBV (including but not limited to telaprevir, boceprevir, sofosbuvir and simeprevir).
4. Confirmed presence of hepatocellular carcinoma indicated on imaging techniques such as CT scan or MRI within 3 months prior to Screening or on an ultrasound performed at Screening (a positive ultrasound result will be confirmed with CT scan or MRI).
5. Any current or past evidence of Child-Pugh C classification.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: GT1B; ombitasvir/paritaprevir/ritonavir 25/150/100 mg once daily (QD) + dasabuvir 250 mg twice daily (BID) + ribavirin (RBV) for 12 weeks in hepatitis C virus (HCV) genotype (GT) 1b-infected participants	Drug: ombitasvir/paritaprevir/ritonavir; tablet; paritaprevir co-formulated with ritonavir and ombitasvir; Other Names: ABT-267 also known as ombitasvir; ABT-450 also known as paritaprevir; ritonavir also known as norvir; Drug: dasabuvir; tablet; Other Names: ABT-333; Drug: ribavirin; tablet
Experimental: Group 2: GT1 Non-B; ombitasvir/paritaprevir/ritonavir 25/150/100 mg QD + dasabuvir 250 mg BID + RBV for 24 weeks in HCV GT1non-b (including GT1a)-infected participants	Drug: ombitasvir/paritaprevir/ritonavir; tablet; paritaprevir co-formulated with ritonavir and ombitasvir; Other Names: ABT-267 also known as ombitasvir; ABT-450 also known as paritaprevir; ritonavir also known as norvir; Drug: dasabuvir; tablet; Other Names: ABT-333; Drug: ribavirin; tablet
Experimental: Group 3: GT4; ombitasvir/paritaprevir/ritonavir 25/150/100 mg QD + RBV for 24 weeks in HCV GT4-infected participants	Drug: ombitasvir/paritaprevir/ritonavir; tablet; paritaprevir co-formulated with ritonavir and ombitasvir; Other Names: ABT-267 also known as ombitasvir; ABT-450 also known as paritaprevir; ritonavir also known as norvir; Drug: ribavirin; tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Participants With Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) in Group 1 and in Group 2	SVR12, defined as HCV RNA < lower limit of quantification (LLOQ) in the SVR12 window (12 weeks after the last actual dose of study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Flanking imputation: for participants with missing HCV RNA at a visit who have an undetectable HCV RNA or unquantifiable HCV RNA at the preceding visit and the succeeding visit, the missing value was imputed as undetectable or unquantifiable. For SVR analyses, if there was no value in the window after the flanking imputation but there was an HCV RNA value after the window, then it was imputed into the SVR window. After above imputations were applied, if there was still no value in the window but there was an HCV RNA value from a local laboratory present, then it was imputed into the SVR window. Otherwise, participants with missing data were counted as failures. The 95% confidence interval was calculated using the Wilson score method.	12 weeks after the last actual dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With SVR12 in Group 3	SVR12, defined as HCV RNA < LLOQ in the SVR12 window (12 weeks after the last actual dose of study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. Flanking imputation: for participants with missing HCV RNA at a visit, who have an undetectable HCV RNA or unquantifiable HCV RNA at the preceding visit and the succeeding visit, the missing value was imputed as undetectable or unquantifiable. For SVR analyses, if there was no value in the window after the flanking imputation but there was an HCV RNA value after the window, then it was imputed into the SVR window. After above imputations were applied, if there was still no value in the window but there was an HCV RNA value from a local laboratory present, then it was imputed into the SVR window. Otherwise, participants with missing data were counted as failures.	12 weeks after the last actual dose of study drug
Percentage of Participants With SVR12 Non-Response Due to Experiencing On-Treatment Virologic Failure	On-treatment virologic failure was defined as: confirmed HCV RNA ≥ LLOQ after HCV RNA < LLOQ during treatment; confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log˅10 IU/mL above nadir) at any time point during treatment; or HCV RNA ≥ LLOQ persistently during treatment with at least 6 weeks (≥ 36 days) of treatment. The 95% confidence interval was calculated using Wilson score method. SVR12 was defined as HCV RNA < LLOQ in the SVR12 window (12 weeks after the last actual dose of study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window.	Up to 24 weeks during treatment
Percentage of Participants With SVR12 Non-Response Due to Experiencing Relapse˅12	Relapse˅12 was defined as confirmed HCV RNA ≥ LLOQ between end of treatment and 12 weeks after last actual dose of active study drug (up to and including the SVR12 window) for a participant with HCV RNA < LLOQ at final treatment visit who completes treatment and has post-treatment HCV RNA data. Completion of treatment was defined as a study drug duration ≥ 77 days for participants assigned to 12 weeks of treatment or ≥ 154 days for participants assigned to 24 weeks of treatment. SVR12 was defined as HCV RNA < LLOQ in the SVR12 window (12 weeks after the last actual dose of study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. The 95% confidence interval was calculated using the Wilson score method.	Up to 12 weeks after the last actual dose of study drug
Percentage of Participants With Improvement From Baseline to Post-Treatment Week 12 in Hepatic Function Tests	Improvement was defined as: increase of more than 0.2 g/L from baseline to post-treatment Week 12 in albumin; decrease of more than 0.3 µmol/L from baseline to post-treatment Week 12 in bilirubin; decrease of more than 5 ng/mL from baseline to post-treatment Week 12 in alpha-fetoprotein; increase of more than 15*10^9/L from baseline to post-treatment Week 12 in platelet count; decrease of more than 0.2 from baseline to post-treatment Week 12 in international normalized ratio.	Up to post-treatment Week 12
Percentage of Participants With Improvement From Baseline to Post-Treatment Week 12 in FibroTest	The FibroTest score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis. Improvement was defined as a decrease of more than 0.2 from baseline to post-treatment Week 12.	Up to post-treatment Week 12
Percentage of Participants With Improvement From Baseline to Post-Treatment Week 12 in Chld-Pugh Score	The The Child-Pugh score uses five clinical measures of liver disease (3 laboratory parameters and 2 clinical assessments) to measure severity of cirrhosis. Scores range from 5 to 15, with higher scores indicating more severity. Improvement was defined as a decrease of 1 or more from baseline to post-treatment Week 12.	Up to post-treatment Week 12
Percentage of Participants With Improvement From Baseline to Post-Treatment Week 12 in Model for End-Stage Liver Disease (MELD) Score	MELD is a scoring system for assessing the severity of chronic liver disease. Scores range from 6 to 40, with higher scores indicating more severity. Improvement was defined as a decrease of 1 or more from baseline to post-treatment Week 12.	Up to post-treatment Week 12

Collaborators and Investigators

• Sponsor: AbbVie
• Investigators: Study Director: Eric Cohen, MD, AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): November 24, 2014
• Primary Completion (Actual): June 13, 2016
• Study Completion (Actual): March 3, 2017

Study Registration Dates

• First Submitted: August 15, 2014
• First Submitted That Met QC Criteria: August 15, 2014
• First Posted (Estimate): August 19, 2014

Study Record Updates

• Last Update Posted (Actual): July 11, 2017
• Last Update Submitted That Met QC Criteria: June 9, 2017
• Last Verified: June 1, 2017

More Information

Terms related to this study

• Keywords: Chronic Hepatitis C; Cirrhosis; Hepatitis C Genotype 1; Hepatitis C; Interferon-Free; Hepatitis C Virus; Child-Pugh B; Hepatitis C Genotype 4; Decompensated Cirrhosis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Fibrosis; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Hepatitis, Chronic; Liver Cirrhosis; Hepatitis C, Chronic; 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: M14-227; 2014-001477-13 (EudraCT Number)