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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ABT-450/r/ABT-267 plus ABT-333 with or without ribavirin (RBV) | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ABT-450/r/ABT-267 | Drug | Tablet for oral use |
|
| Measure | Description | Time Frame |
|---|---|---|
| All-Cause Death: Time to Event | 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). | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
| Liver-Related Death: Time to Event | 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). | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
| Liver Decompensation: Time to Event | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 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. | 12 weeks after the last actual dose of study drug |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| ABBVIE INC. | AbbVie | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| St. Josephs Hospital and Med Center /ID# 127800 | Phoenix | Arizona | 85013 | United States | ||
| Franco Felizarta, Md /Id# 126569 |
AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
For details on when studies are available for sharing, please refer to the link below.
Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Use Agreement (DUA). For more information on the process, or to submit a request, visit the following link.
Safety population: All participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug
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| ID | Title | Description |
|---|---|---|
| FG000 | ABT-450/r/ABT-267 Plus ABT-333 With or Without 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 19, 2014 | Mar 11, 2022 |
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| ABT-333 | Drug | Tablet for oral use |
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| Ribavirin (RBV) | Drug | Ribavirin was provided as 200 mg tablets, and dosed based on weight, 1000 to 1200 mg divided twice daily per local label. For example, for participants weighing < 75 kg, RBV may have been taken orally as 2 tablets in the morning and 3 tablets in the evening which corresponds to a 1000 mg total daily dose. For participants weighing ≥ 75 kg, RBV may have been taken orally as 3 tablets in the morning and 3 tablets in the evening which corresponds to a 1200 mg total daily dose. |
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| At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
| Liver Transplantation: Time to Event | 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). | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
| Hepatocellular Carcinoma: Time to Event | 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). | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
| All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | 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. | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
| 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 |
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. |
| From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24 |
| 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 | 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. | From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24 |
| 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 | 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. | From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24 |
| Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets | 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%. | Up to Treatment Week 24 |
| Bakersfield |
| California |
| 93301 |
| United States |
| Ruane Clinical Research Group /ID# 126577 | Los Angeles | California | 90036 | United States |
| California Pacific Medical Center /ID# 128681 | San Francisco | California | 94115 | United States |
| Univ of Colorado Cancer Center /ID# 126568 | Aurora | Colorado | 80045 | United States |
| Medstar Health Research Institute /ID# 128683 | Washington D.C. | District of Columbia | 20010 | United States |
| Bach and Godofsky Infec Dis /ID# 128685 | Bradenton | Florida | 34209 | United States |
| University of Florida - Archer /ID# 127787 | Gainesville | Florida | 32610 | United States |
| Encore Borland-Groover Clinical Research /Id# 127781 | Jacksonville | Florida | 32256 | United States |
| University of Miami /ID# 127622 | Miami | Florida | 33136 | United States |
| South Florida Ctr Gastro, P.A. /ID# 126567 | Wellington | Florida | 33414 | United States |
| Atlanta Gastro Assoc /ID# 126571 | Atlanta | Georgia | 30342 | United States |
| Northwestern University Feinberg School of Medicine /ID# 128684 | Chicago | Illinois | 60611-2927 | United States |
| The University of Chicago Medical Center /ID# 126576 | Chicago | Illinois | 60637-1443 | United States |
| Duplicate_Indiana University Health /ID# 126573 | Indianapolis | Indiana | 46202 | United States |
| Tulane University /ID# 127779 | New Orleans | Louisiana | 70112-2699 | United States |
| Louisana Research Center, LLC /ID# 126561 | Shreveport | Louisiana | 71105-6800 | United States |
| Johns Hopkins University /ID# 127791 | Baltimore | Maryland | 21287 | United States |
| Digestive Disease Associates - Catonsville /ID# 127624 | Catonsville | Maryland | 21228 | United States |
| Beth Israel Deaconess Medical Center /ID# 126560 | Boston | Massachusetts | 02215-5400 | United States |
| Henry Ford Health System /ID# 127783 | Detroit | Michigan | 48202 | United States |
| Minnesota Gastroenterology PA /ID# 126579 | Plymouth | Minnesota | 55446 | United States |
| St. Louis University /ID# 126564 | St Louis | Missouri | 63104 | United States |
| AGA Clinical Research Associates, LLC /ID# 126578 | Egg Harbor | New Jersey | 08234 | United States |
| Rutgers New Jersey School of Medicine /ID# 128686 | Newark | New Jersey | 07103 | United States |
| University of New Mexico /ID# 128859 | Albuquerque | New Mexico | 87102-4517 | United States |
| Southwest Care Center /ID# 127784 | Santa Fe | New Mexico | 87505 | United States |
| North Shore University Hospital /ID# 126565 | New Hyde Park | New York | 11040 | United States |
| The Mount Sinai Hospital /ID# 128682 | New York | New York | 10029 | United States |
| Columbia Univ Medical Center /ID# 126566 | New York | New York | 10032-3725 | United States |
| Columbia Univ Medical Center /ID# 127621 | New York | New York | 10032-3725 | United States |
| Premier Medical Group - GI Division /ID# 127793 | Poughkeepsie | New York | 12601 | United States |
| Univ Rochester Med Ctr /ID# 127655 | Rochester | New York | 14642 | United States |
| Atrium Health Carolinas Medical Center /ID# 127632 | Charlotte | North Carolina | 28203 | United States |
| Carolinas Center For Liver Dis /ID# 127788 | Statesville | North Carolina | 28677 | United States |
| University of Cincinnati Physicians Company, LLC /ID# 127790 | Cincinnati | Ohio | 45267-2827 | United States |
| Options Health Research, LLC /ID# 127630 | Tulsa | Oklahoma | 74104 | United States |
| University Gastroenterology /ID# 127789 | Providence | Rhode Island | 02905 | United States |
| Gastro One /ID# 127792 | Germantown | Tennessee | 38138 | United States |
| Inquest Clinical Research /ID# 126574 | Baytown | Texas | 77521-2415 | United States |
| Cure C Consortium /ID# 126570 | Houston | Texas | 77004 | United States |
| Liver Associates of Texas, P.A /ID# 126563 | Houston | Texas | 77030-2783 | United States |
| Austin Institute for Clinical Research /ID# 126562 | Pflugerville | Texas | 78660 | United States |
| TX Liver Inst, Americ Res Corp /ID# 127623 | San Antonio | Texas | 78215 | United States |
| Clinical Research Ctrs America /ID# 127780 | Murray | Utah | 84123 | United States |
| Virginia Mason - Seattle Orthapedics /ID# 130288 | Seattle | Washington | 98101 | United States |
| University of Washington /ID# 127785 | Seattle | Washington | 98109 | United States |
| Dean Clinic /ID# 126575 | Madison | Wisconsin | 53715 | United States |
| COMPLETED |
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| NOT COMPLETED |
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Safety population: All participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug
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| ID | Title | Description |
|---|---|---|
| BG000 | ABT-450/r/ABT-267 Plus ABT-333 With or Without 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. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants | No |
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| Race/Ethnicity, Customized | Count of Participants | Participants | No |
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| HCV Genotype 1 Subtype | Count of Participants | Participants | No |
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| Prior HCV Treatment History | Count of Participants | Participants | No |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Primary | All-Cause Death: Time to Event | 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). | Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug | Posted | Number | 95% Confidence Interval | percentage of participants | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
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| Primary | Liver-Related Death: Time to Event | 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). | Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug | Posted | Number | 95% Confidence Interval | percentage of participants | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
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| Primary | Liver Decompensation: Time to Event | 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). | Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug | Posted | Number | 95% Confidence Interval | percentage of participants | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
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| Primary | Liver Transplantation: Time to Event | 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). | Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug | Posted | Number | 95% Confidence Interval | percentage of participants | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
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| Primary | Hepatocellular Carcinoma: Time to Event | 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). | Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug | Posted | Number | 95% Confidence Interval | percentage of participants | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
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| Primary | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | 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. | Intent-to-treat (ITT) population: all enrolled participants in this study (TOPAZ-II; M14-222; ITT-II) and in companion study M14-423 (TOPAZ-I; NCT02219490; ITT-I) who received at least one dose of study drug | Posted | Number | 95% Confidence Interval | percentage of participants | At Post-Treatment Weeks 52, 104, 156, 208, and 260 |
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| Secondary | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 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. | ITT-II population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug. Flanking imputation, where applicable, was used to impute missing data. After applying flanking imputation, if there was no value in the window but there was an HCV RNA value from a local laboratory present, then it was to be imputed into the SVR window. Otherwise, participants with missing data were counted as failures. | Posted | Number | 95% Confidence Interval | percentage of participants | 12 weeks after the last actual dose of study drug |
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| Secondary | 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 | 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. | ITT-II population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug and had both baseline and post-treatment data | Posted | Mean | Standard Deviation | units on a scale | From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24 |
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| Secondary | 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 | 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. | ITT-II population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug and had both baseline and post-treatment data | Posted | Mean | Standard Deviation | units on a scale | From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24 |
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| Secondary | 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 | 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. | ITT-II population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug who had both baseline and post-treatment data. | Posted | Mean | Standard Deviation | units on a scale | From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24 |
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| Secondary | Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets | 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%. | Safety population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug with available data | Posted | Mean | Standard Deviation | percentage of tablets taken | Up to Treatment Week 24 |
|
All-cause mortality is reported from enrollment to the end of study, up to five years of follow-up. Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the first dose of study drug until 30 days after the last study drug administration, up to 213 days. After Post-Treatment Week 4 until the end of the study, only SAE of death was to be collected.
All-cause mortality and adverse events: all participants in this study (M14-222; TOPAZ-II) who received at least one dose of study drug
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ABT-450/r/ABT-267 Plus ABT-333 With or Without 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. | 19 | 615 | 25 | 615 | 381 | 615 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| CORONARY ARTERY DISEASE | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| PERICARDITIS | Cardiac disorders | MedDRA 23.0 | Systematic Assessment |
| |
| HYPERADRENOCORTICISM | Endocrine disorders | MedDRA 23.0 | Systematic Assessment |
| |
| INGUINAL HERNIA | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| SMALL INTESTINAL OBSTRUCTION | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| CHEST PAIN | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| CHOLECYSTITIS | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| ALLERGIC OEDEMA | Immune system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| BRONCHITIS | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| PERITONITIS | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| PNEUMONIA | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| PNEUMONIA PNEUMOCOCCAL | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| ALCOHOL POISONING | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| ANKLE FRACTURE | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| MULTIPLE FRACTURES | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| OVERDOSE | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
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| RIB FRACTURE | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| SPINAL FRACTURE | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| UPPER LIMB FRACTURE | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| DIABETES MELLITUS | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| HEPATOCELLULAR CARCINOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| LUNG ADENOCARCINOMA | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| PANCREATIC CARCINOMA METASTATIC | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| ALCOHOL WITHDRAWAL SYNDROME | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| MENTAL STATUS CHANGES | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| SCHIZOAFFECTIVE DISORDER | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| SUICIDE ATTEMPT | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| ACUTE KIDNEY INJURY | Renal and urinary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| BRONCHOSPASM | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| CHRONIC OBSTRUCTIVE PULMONARY DISEASE | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| PLEURISY | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| HYPOTENSION | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| ANAEMIA | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| DIARRHOEA | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| NAUSEA | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| VOMITING | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
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| FATIGUE | General disorders | MedDRA 23.0 | Systematic Assessment |
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| DIZZINESS | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| HEADACHE | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
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| INSOMNIA | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
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| COUGH | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
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| PRURITUS | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| RASH | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
|
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Medical Services | AbbVie | 800-633-9110 | abbvieclinicaltrials@abbvie.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 7, 2015 | Mar 11, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D019698 | Hepatitis C, Chronic |
| D006526 | Hepatitis C |
| D005355 | Fibrosis |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D006525 | Hepatitis, Viral, Human |
| D014777 | Virus Diseases |
| D018178 | Flaviviridae Infections |
| D012327 | RNA Virus Infections |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C585405 | paritaprevir |
| C586094 | ombitasvir |
| C588260 | dasabuvir |
| D012254 | Ribavirin |
| ID | Term |
|---|---|
| D012263 | Ribonucleosides |
| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
Not provided
Not provided
| Asian |
|
| American Indian or Alaska Native |
|
| Native Hawaiian or Other Pacific Islander |
|
| Multiple |
|
| GT1 Non-b without cirrhosis |
|
| GT1 Non-b with compensated cirrhosis |
|
| Kaplan-Meier estimate at PT Week 156 |
|
| Kaplan-Meier estimate at PT Week 208 |
|
| Kaplan-Meier estimate at PT Week 260 |
|
| Cox proportional hazards model |
| <0.001 |
| Cox Proportional Hazard Ratio |
| 0.126 |
| 2-Sided |
| 95 |
| 0.044 |
| 0.358 |
The estimated value represents the hazard ratio for developing the event in the group of participants in studies M14-222 and M14-423 who achieved SVR12 compared to the group of participants in studies M14-222 and M14-423 who didn't achieve SVR12. |
| Superiority |
| OG001 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 |
SVR12 was 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. |
|
|
|
| OG001 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 |
SVR12 was 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. |
|
|
|
| OG001 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 |
SVR12 was 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. |
|
|
|
| OG001 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 |
SVR12 was 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. |
|
|
|
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 |
SVR12 was 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. |
|
|
|
| Units | Counts |
|---|
| Participants |
|
|
| OG002 |
| Baseline Fibrosis Stage F3 |
Participants in study M14-222 with a baseline fibrosis stage of F3 |
| OG003 | Baseline Fibrosis Stage F4 | Participants in study M14-222 with a baseline fibrosis stage of F4 |
|
|
|
| OG002 |
| Baseline Fibrosis Stage F3 |
Participants in study M14-222 with a baseline fibrosis stage of F3 |
| OG003 | Baseline Fibrosis Stage F4 | Participants in study M14-222 with a baseline fibrosis stage of F4 |
|
|
|
Participants in study M14-222 with a baseline fibrosis stage of F3
| OG003 | Baseline Fibrosis Stage F4 | Participants in study M14-222 with a baseline fibrosis stage of F4 |
|
|
|
| Weight-based Ribavirin (RBV) |
Participants with HCV GT1a without cirrhosis and those with HCV GT1b with cirrhosis received weight-based ribavirin (RBV; 1000 to 1200 mg divided twice daily per local label) for 12 weeks. Participants with HCV GT1a with cirrhosis received weight-based RBV per local label for 24 weeks. Ribavirin was provided as 200 mg tablets, and dosed based on weight, 1000 to 1200 mg divided twice daily per local label. For example, for participants weighing < 75 kg, RBV may have been taken orally as 2 tablets in the morning and 3 tablets in the evening which corresponds to a 1000 mg total daily dose. For participants weighing ≥ 75 kg, RBV may have been taken orally as 3 tablets in the morning and 3 tablets in the evening which corresponds to a 1200 mg total daily dose. |
|
|
|
|
|