Back to resultsA 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)
Primary Purpose
Chronic Hepatitis C, Decompensated Cirrhosis, Hepatitis C Virus
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
ombitasvir/paritaprevir/ritonavir
dasabuvir
ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C focused on measuring Cirrhosis, Hepatitis C, Child-Pugh B, Hepatitis C Genotype 4, Interferon-Free, Hepatitis C Genotype 1, Chronic Hepatitis C, Decompensated Cirrhosis, Hepatitis C Virus
Eligibility Criteria
Inclusion Criteria:
- 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.
- Evidence of cirrhosis by prior liver biopsy, FibroScan or by radiograph (i.e., computed tomography [CT] scan or magnetic resonance imaging [MRI]).
- Child-Pugh Score of 7 - 9, inclusive, at time of Screening.
Exclusion Criteria:
- Women who are pregnant or breastfeeding.
- Positive test result for Hepatitis B surface antigen (HbsAg) or anti-HIV antibodies (HIV Ab).
- 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).
- 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).
- Any current or past evidence of Child-Pugh C classification.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
Group 1: GT1B
Group 2: GT1 Non-B
Group 3: GT4
Arm Description
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
ombitasvir/paritaprevir/ritonavir 25/150/100 mg QD + dasabuvir 250 mg BID + RBV for 24 weeks in HCV GT1non-b (including GT1a)-infected participants
ombitasvir/paritaprevir/ritonavir 25/150/100 mg QD + RBV for 24 weeks in HCV GT4-infected participants
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02219477
Brief Title
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
Acronym
TURQUOISE-CPB
Official Title
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)
Study Type
Interventional
2. Study Status
Record Verification Date
June 2017
Overall Recruitment Status
Completed
Study Start Date
November 24, 2014 (Actual)
Primary Completion Date
June 13, 2016 (Actual)
Study Completion Date
March 3, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C, Decompensated Cirrhosis, Hepatitis C Virus
Keywords
Cirrhosis, Hepatitis C, Child-Pugh B, Hepatitis C Genotype 4, Interferon-Free, Hepatitis C Genotype 1, Chronic Hepatitis C, Decompensated Cirrhosis, Hepatitis C Virus
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group 1: GT1B
Arm Type
Experimental
Arm Description
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
Arm Title
Group 2: GT1 Non-B
Arm Type
Experimental
Arm Description
ombitasvir/paritaprevir/ritonavir 25/150/100 mg QD + dasabuvir 250 mg BID + RBV for 24 weeks in HCV GT1non-b (including GT1a)-infected participants
Arm Title
Group 3: GT4
Arm Type
Experimental
Arm Description
ombitasvir/paritaprevir/ritonavir 25/150/100 mg QD + RBV for 24 weeks in HCV GT4-infected participants
Intervention Type
Drug
Intervention Name(s)
ombitasvir/paritaprevir/ritonavir
Other Intervention Name(s)
ABT-267 also known as ombitasvir, ABT-450 also known as paritaprevir, ritonavir also known as norvir
Intervention Description
tablet; paritaprevir co-formulated with ritonavir and ombitasvir
Intervention Type
Drug
Intervention Name(s)
dasabuvir
Other Intervention Name(s)
ABT-333
Intervention Description
tablet
Intervention Type
Drug
Intervention Name(s)
ribavirin
Intervention Description
tablet
Primary Outcome Measure Information:
Title
Percentages of Participants With Sustained Virologic Response 12 Weeks Post-Treatment (SVR12) in Group 1 and in Group 2
Description
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.
Time Frame
12 weeks after the last actual dose of study drug
Secondary Outcome Measure Information:
Title
Percentage of Participants With SVR12 in Group 3
Description
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.
Time Frame
12 weeks after the last actual dose of study drug
Title
Percentage of Participants With SVR12 Non-Response Due to Experiencing On-Treatment Virologic Failure
Description
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.
Time Frame
Up to 24 weeks during treatment
Title
Percentage of Participants With SVR12 Non-Response Due to Experiencing Relapse˅12
Description
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.
Time Frame
Up to 12 weeks after the last actual dose of study drug
Title
Percentage of Participants With Improvement From Baseline to Post-Treatment Week 12 in Hepatic Function Tests
Description
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.
Time Frame
Up to post-treatment Week 12
Title
Percentage of Participants With Improvement From Baseline to Post-Treatment Week 12 in FibroTest
Description
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.
Time Frame
Up to post-treatment Week 12
Title
Percentage of Participants With Improvement From Baseline to Post-Treatment Week 12 in Chld-Pugh Score
Description
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.
Time Frame
Up to post-treatment Week 12
Title
Percentage of Participants With Improvement From Baseline to Post-Treatment Week 12 in Model for End-Stage Liver Disease (MELD) Score
Description
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.
Time Frame
Up to post-treatment Week 12
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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.
Evidence of cirrhosis by prior liver biopsy, FibroScan or by radiograph (i.e., computed tomography [CT] scan or magnetic resonance imaging [MRI]).
Child-Pugh Score of 7 - 9, inclusive, at time of Screening.
Exclusion Criteria:
Women who are pregnant or breastfeeding.
Positive test result for Hepatitis B surface antigen (HbsAg) or anti-HIV antibodies (HIV Ab).
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).
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).
Any current or past evidence of Child-Pugh C classification.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Eric Cohen, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
12. IPD Sharing Statement
Learn more about this trial
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
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