A Study to Evaluate Long-term Outcomes Following Treatment With ABT-450/Ritonavir/ABT-267 (ABT-450/r/ABT-267) and ABT-333 With or Without Ribavirin (RBV) in Adults With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection
- Conditions
- Chronic Hepatitis C Virus (HCV) Infection Genotype 1
- Interventions
- Registration Number
- NCT02167945
- Lead Sponsor
- AbbVie
- Brief Summary
The purpose of this study was to evaluate the effect of treatment with ABT-450 co-formulated with ritonavir and ABT-267 (ABT-450/r/ABT-267) and ABT-333; 3-DAA regimen, with or without ribavirin (RBV) in adults with chronic hepatitis C virus genotype 1 (HCV GT1) infection.
- Detailed Description
This study (TOPAZ-II; M14-222), was a Phase 3b, open-label, multicenter study conducted in the United States which, together with its companion study TOPAZ-I (M14-423; NCT02219490) conducted outside of the United States, was designed with the primary objective of assessing the effect of treatment response on long-term clinical outcomes in adults with chronic HCV GT1 infection with or without compensated cirrhosis, who were either treatment-naïve or interferon/ribavirin (IFN/RBV) treatment- experienced. In both studies, participants were treated with the 3-DAA regimen with or without RBV. This study consisted of a screening period of up to 42 days, a treatment period of either 12 weeks for HCV GT1a-infected subjects without cirrhosis and for HCV GT1b-infected subjects without cirrhosis or with compensated cirrhosis or 24 weeks for GT1a-infected participants with compensated cirrhosis, and a 260-week post-treatment period.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 615
- Females must be post-menopausal for more than 2 years or surgically sterile or practicing specific forms of birth control
- Chronic hepatitis C, genotype 1-infection (HCV RNA level greater than 1,000 IU/mL at screening)
- HCV genotype 1 infection per screening laboratory result
- Use of contraindicated medications within 2 weeks of dosing
- Abnormal laboratory tests
- Positive hepatitis B surface antigen and anti-Human Immunodeficiency Virus Antibody
- History of solid organ transplant, clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation
- Presence of hepatocellular carcinoma at screening
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV) Ribavirin (RBV) Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks. ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV) ABT-333 Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks. ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV) ABT-450/r/ABT-267 Participants with HCV GT1b without cirrhosis received the 3-DAA (ABT-450/ritonavir/ABT-267 and ABT-333) regimen: two 75 mg ABT-450/50 mg ritonavir/12.5 mg ABT-267 tablets taken orally every morning (QD) and one ABT-333 250 mg tablet taken orally twice a day (BID) for 12 weeks. Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received the 3-DAA regimen and weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received the 3-DAA regimen and weight-based RBV per local label for 24 weeks.
- Primary Outcome Measures
Name Time Method Liver-Related Death: Time to Event At Post-Treatment Weeks 52, 104, 156, 208, and 260 Time to liver-related death was defined as number of days from the 1st day of study drug dosing for the participant to date of liver-related death. All liver-related deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver-related death. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver-related death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
Liver Decompensation: Time to Event At Post-Treatment Weeks 52, 104, 156, 208, and 260 Time to liver decompensation was defined as number of days from the 1st day of study drug dosing for the participant to the date of liver decompensation. All liver decompensation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver decompensation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver decompensation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
All-Cause Death: Time to Event At Post-Treatment Weeks 52, 104, 156, 208, and 260 Time to all-cause death was defined as the number of days from the first day of study drug dosing for the participant to the date of death. All deaths were to be included, regardless of whether the death occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not die, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of all-cause death included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
Liver Transplantation: Time to Event At Post-Treatment Weeks 52, 104, 156, 208, and 260 Time to liver transplantation was defined as number of days from the 1st day of study drug dosing for the participant to date of liver transplantation. All liver transplantation was to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for liver transplantation. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of liver transplantation included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
Hepatocellular Carcinoma: Time to Event At Post-Treatment Weeks 52, 104, 156, 208, and 260 Time to hepatocellular carcinoma was defined as number of days from the 1st day of study drug dosing for the participant to date of hepatocellular carcinoma. All hepatocellular carcinoma was to be included, whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant didn't experience the event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment of clinical outcomes. For those with no post-baseline assessment, their data was to be censored on the 1st day of study drug dosing. All-cause death was a censoring event for hepatocellular carcinoma. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. The pre-specified analysis of hepatocellular carcinoma included pooled data from TOPAZ-II (this study) and the companion study TOPAZ-I (M14-423; NCT02219490).
All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event At Post-Treatment Weeks 52, 104, 156, 208, and 260 Time to the composite of clinical outcomes is the time to the first occurrence of all-cause death, liver-related death, liver decompensation, liver transplantation, or hepatocellular carcinoma. All first occurrences were to be included, regardless of whether it occurred while the participant was still taking study drug or had previously discontinued study drug. If the participant did not experience any of these events, their data was to be censored at the date of their last available assessment of clinical outcomes. For participants with no post-baseline assessment, the participant's data was to be censored on the first day of study drug dosing. The event-free survival rates were estimated using Kaplan-Meier methodology and incidence estimates are presented with 95% confidence intervals. Pre-specified analysis included pooled data from this study and from TOPAZ-I; NCT02219490.
- Secondary Outcome Measures
Name Time Method Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Physical Component Summary (PCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24 From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24 The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of 4 weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health. Positive numbers indicate improvement from baseline.
Mean Change From Baseline in Short Form 36 Version 2.0 (SF-36 V2) Mental Component Summary (MCS) Score at Post-Treatment Week 12 and Post-Treatment Week 24 From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24 The SF-36v2 is a non-disease specific Health Related Quality of Life (HRQoL) instrument with extensive use in multiple disease states. The SF-36v2 instrument comprises 36 total items (questions) targeting a subject's functional health and well-being in 8 domains (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health) with a recall period of 4 weeks. Domain scores are aggregated into a Physical Component Summary (PCS) score and a Mental Component Summary (MCS) score. SF-36v2 scores for each domain and PCS/MCS range from 0-100: higher scores indicate a better state of health. Positive numbers indicate improvement from baseline.
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) 12 weeks after the last actual dose of study drug SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets Up to Treatment Week 24 Treatment compliance was calculated as the percentage of tablets taken (presumed as \[tablets dispensed-tablets returned\]) relative to the total tablets, respectively, expected to be taken. Study drug interruptions due to an adverse event or other planned interruptions recorded on the electronic case report form (eCRF) were to be subtracted from the duration. For compliance to ribavirin (RBV), RBV dose modifications due to adverse events, toxicity management, or weight changes as recorded on the RBV Dose Modifications eCRF were to be used to modify the total number of tablets that should have been taken. A participant is considered to be compliant if the percentage is between 80% and 120%.
Mean Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Post-Treatment Week 12 and Post-Treatment Week 24 From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24 The FACIT-F is a symptom specific instrument with a focus on measuring fatigue in a variety of chronic diseases or health conditions. It was originally developed from interviews with oncology patients and clinical experts to assess anemia-associated fatigue. Its 13-item-version assesses peripheral, central, or mixed fatigue with a recall period of 7 days and yields a summed total score ranging between 0 and 52. Higher FACIT-F scores indicate a lesser degree of fatigue. Positive numbers indicate improvement from baseline.
Trial Locations
- Locations (48)
St. Josephs Hospital and Med Center /ID# 127800
🇺🇸Phoenix, Arizona, United States
Univ of Colorado Cancer Center /ID# 126568
🇺🇸Aurora, Colorado, United States
Encore Borland-Groover Clinical Research /Id# 127781
🇺🇸Jacksonville, Florida, United States
South Florida Ctr Gastro, P.A. /ID# 126567
🇺🇸Wellington, Florida, United States
Louisana Research Center, LLC /ID# 126561
🇺🇸Shreveport, Louisiana, United States
Henry Ford Health System /ID# 127783
🇺🇸Detroit, Michigan, United States
Southwest Care Center /ID# 127784
🇺🇸Santa Fe, New Mexico, United States
St. Louis University /ID# 126564
🇺🇸Saint Louis, Missouri, United States
AGA Clinical Research Associates, LLC /ID# 126578
🇺🇸Egg Harbor Township, New Jersey, United States
Rutgers New Jersey School of Medicine /ID# 128686
🇺🇸Newark, New Jersey, United States
University of New Mexico /ID# 128859
🇺🇸Albuquerque, New Mexico, United States
Columbia Univ Medical Center /ID# 126566
🇺🇸New York, New York, United States
North Shore University Hospital /ID# 126565
🇺🇸New Hyde Park, New York, United States
The Mount Sinai Hospital /ID# 128682
🇺🇸New York, New York, United States
Columbia Univ Medical Center /ID# 127621
🇺🇸New York, New York, United States
Premier Medical Group - GI Division /ID# 127793
🇺🇸Poughkeepsie, New York, United States
Univ Rochester Med Ctr /ID# 127655
🇺🇸Rochester, New York, United States
Atrium Health Carolinas Medical Center /ID# 127632
🇺🇸Charlotte, North Carolina, United States
Options Health Research, LLC /ID# 127630
🇺🇸Tulsa, Oklahoma, United States
University Gastroenterology /ID# 127789
🇺🇸Providence, Rhode Island, United States
Inquest Clinical Research /ID# 126574
🇺🇸Baytown, Texas, United States
Austin Institute for Clinical Research /ID# 126562
🇺🇸Pflugerville, Texas, United States
Clinical Research Ctrs America /ID# 127780
🇺🇸Murray, Utah, United States
Dean Clinic /ID# 126575
🇺🇸Madison, Wisconsin, United States
Franco Felizarta, Md /Id# 126569
🇺🇸Bakersfield, California, United States
Ruane Clinical Research Group /ID# 126577
🇺🇸Los Angeles, California, United States
Atlanta Gastro Assoc /ID# 126571
🇺🇸Atlanta, Georgia, United States
Northwestern University Feinberg School of Medicine /ID# 128684
🇺🇸Chicago, Illinois, United States
The University of Chicago Medical Center /ID# 126576
🇺🇸Chicago, Illinois, United States
Beth Israel Deaconess Medical Center /ID# 126560
🇺🇸Boston, Massachusetts, United States
Carolinas Center For Liver Dis /ID# 127788
🇺🇸Statesville, North Carolina, United States
Cure C Consortium /ID# 126570
🇺🇸Houston, Texas, United States
Liver Associates of Texas, P.A /ID# 126563
🇺🇸Houston, Texas, United States
Virginia Mason - Seattle Orthapedics /ID# 130288
🇺🇸Seattle, Washington, United States
University of Washington /ID# 127785
🇺🇸Seattle, Washington, United States
California Pacific Medical Center /ID# 128681
🇺🇸San Francisco, California, United States
University of Miami /ID# 127622
🇺🇸Miami, Florida, United States
Duplicate_Indiana University Health /ID# 126573
🇺🇸Indianapolis, Indiana, United States
University of Cincinnati Physicians Company, LLC /ID# 127790
🇺🇸Cincinnati, Ohio, United States
TX Liver Inst, Americ Res Corp /ID# 127623
🇺🇸San Antonio, Texas, United States
Minnesota Gastroenterology PA /ID# 126579
🇺🇸Plymouth, Minnesota, United States
Bach and Godofsky Infec Dis /ID# 128685
🇺🇸Bradenton, Florida, United States
Medstar Health Research Institute /ID# 128683
🇺🇸Washington, District of Columbia, United States
Gastro One /ID# 127792
🇺🇸Germantown, Tennessee, United States
Johns Hopkins University /ID# 127791
🇺🇸Baltimore, Maryland, United States
Tulane University /ID# 127779
🇺🇸New Orleans, Louisiana, United States
University of Florida - Archer /ID# 127787
🇺🇸Gainesville, Florida, United States
Digestive Disease Associates - Catonsville /ID# 127624
🇺🇸Catonsville, Maryland, United States