Chronic Hepatitis C Virus (HCV) Infection Genotype 1
Conditions
Keywords
Hepatitis C Genotype 1, Compensated Cirrhosis, Cirrhosis, Naïve, Hepatitis C, Hepatitis C Virus, Treatment-Experienced, Relapser, Null responder, Non responder
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.
Interventions
Tablet for oral use
DRUGABT-333
Tablet for oral use
DRUGRibavirin (RBV)
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.
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
1. Females must be post-menopausal for more than 2 years or surgically sterile or practicing specific forms of birth control 2. Chronic hepatitis C, genotype 1-infection (HCV RNA level greater than 1,000 IU/mL at screening) 3. HCV genotype 1 infection per screening laboratory result
Exclusion criteria
1. Use of contraindicated medications within 2 weeks of dosing 2. Abnormal laboratory tests 3. Positive hepatitis B surface antigen and anti-Human Immunodeficiency Virus Antibody 4. History of solid organ transplant, clinical evidence of Child-Pugh B or C classification or clinical history of liver decompensation 5. Presence of hepatocellular carcinoma at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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-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). |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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%. |
| 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. |
Countries
United States
Participant flow
Pre-assignment details
Safety population: All participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug
Participants by arm
| Arm | Count |
|---|---|
| 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. | 615 |
| Total | 615 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 16 |
| Overall Study | COVID-19 logistical restrictions | 6 |
| Overall Study | Lost to Follow-up | 122 |
| Overall Study | Other, not specified | 63 |
| Overall Study | Withdrew Consent | 42 |
Baseline characteristics
| Characteristic | ABT-450/r/ABT-267 Plus ABT-333 With or Without Ribavirin (RBV) |
|---|---|
| Age, Continuous | 54.5 years STANDARD_DEVIATION 10.84 |
| HCV Genotype 1 Subtype GT1b with compensated cirrhosis | 22 Participants |
| HCV Genotype 1 Subtype GT1b without cirrhosis | 141 Participants |
| HCV Genotype 1 Subtype GT1 Non-b with compensated cirrhosis | 93 Participants |
| HCV Genotype 1 Subtype GT1 Non-b without cirrhosis | 359 Participants |
| Prior HCV Treatment History Treatment Experienced | 178 Participants |
| Prior HCV Treatment History Treatment Naïve | 437 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Black or African American | 84 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized White | 520 Participants |
| Sex: Female, Male Female | 243 Participants |
| Sex: Female, Male Male | 372 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 19 / 615 |
| other Total, other adverse events | 381 / 615 |
| serious Total, serious adverse events | 25 / 615 |
Outcome results
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.
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 104 | 11.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 208 | 11.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 156 | 11.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 260 | 11.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 52 | 11.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 260 | 3.2 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 52 | 0.5 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 104 | 1.2 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 156 | 1.9 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death, Liver-Related Death, Liver Decompensation, Liver Transplantation, Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 208 | 2.3 percentage of participants |
Comparison: Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.p-value: <0.001Log-rank test
Comparison: A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).p-value: <0.00195% CI: [0.057, 0.313]Cox proportional hazards model
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).
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 104 | 8.3 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 208 | 8.3 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 156 | 8.3 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 260 | 8.3 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 52 | 8.3 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 260 | 2.0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 52 | 0.1 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 104 | 0.7 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 156 | 1.2 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | All-Cause Death: Time to Event | Kaplan-Meier estimate at PT Week 208 | 1.5 percentage of participants |
Comparison: Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.p-value: <0.001Log-rank test
Comparison: A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).p-value: <0.00195% CI: [0.044, 0.358]Cox proportional hazards model
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).
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 104 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 208 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 156 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 260 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 52 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 260 | 0.9 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 52 | 0.2 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 104 | 0.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 156 | 0.5 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Hepatocellular Carcinoma: Time to Event | Kaplan-Meier estimate at PT Week 208 | 0.6 percentage of participants |
Comparison: Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.p-value: 0.608Log-rank test
Comparison: A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).p-value: 0.992Cox proportional hazards model
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).
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 104 | 4.5 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 208 | 4.5 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 156 | 4.5 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 260 | 4.5 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 52 | 4.5 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 260 | 0.5 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 52 | 0.2 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 104 | 0.2 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 156 | 0.3 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Decompensation: Time to Event | Kaplan-Meier estimate at PT Week 208 | 0.3 percentage of participants |
Comparison: Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.p-value: <0.001Log-rank test
Comparison: A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).p-value: <0.00195% CI: [0.009, 0.156]Cox proportional hazards model
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).
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 104 | 1.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 208 | 1.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 156 | 1.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 260 | 1.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 52 | 1.4 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 260 | 0.1 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 52 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 104 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 156 | 0.1 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver-Related Death: Time to Event | Kaplan-Meier estimate at PT Week 208 | 0.1 percentage of participants |
Comparison: Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.p-value: <0.001Log-rank test
Comparison: A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).p-value: 0.00795% CI: [0.003, 0.38]Cox proportional hazards model
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).
Time frame: At Post-Treatment Weeks 52, 104, 156, 208, and 260
Population: 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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 104 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 208 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 156 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 260 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 52 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 260 | 0.2 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 52 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 104 | 0 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 156 | 0.1 percentage of participants |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Liver Transplantation: Time to Event | Kaplan-Meier estimate at PT Week 208 | 0.1 percentage of participants |
Comparison: Comparisons between participants in studies M14-222 and M14-423 who achieved SVR12 and those who did not were performed using a log-rank test.p-value: 0.86Log-rank test
Comparison: A Cox proportional hazards (PH) model was constructed. The covariates for the model included baseline age, BMI, HCV genotype 1 subtype (1b, non-1b), IL28B genotype (CC, non-CC), prior treatment history (naive, experienced), baseline HCV RNA levels, baseline fibrosis stage (F0-1, F2, F3, F4), baseline albumin, baseline creatinine clearance, baseline platelet count, history of diabetes (yes, no), APRI, race (white, other), and alcohol use status (current, former, non-drinker).p-value: 0.997Cox proportional hazards model
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.
Time frame: From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24
Population: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | 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 | At Post-treatment Week 12 | 3.9 units on a scale | Standard Deviation 9.66 |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | 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 | At Post-treatment Week 24 | 3.9 units on a scale | Standard Deviation 10.46 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | 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 | At Post-treatment Week 24 | 3.1 units on a scale | Standard Deviation 6.85 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | 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 | At Post-treatment Week 12 | 2.0 units on a scale | Standard Deviation 9.12 |
| Baseline Fibrosis Stage F3 | 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 | At Post-treatment Week 12 | 2.0 units on a scale | Standard Deviation 8.63 |
| Baseline Fibrosis Stage F3 | 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 | At Post-treatment Week 24 | 2.3 units on a scale | Standard Deviation 9.27 |
| Baseline Fibrosis Stage F4 | 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 | At Post-treatment Week 12 | 3.0 units on a scale | Standard Deviation 9.57 |
| Baseline Fibrosis Stage F4 | 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 | At Post-treatment Week 24 | 2.6 units on a scale | Standard Deviation 10.88 |
Comparison: F0-F1 vs F2 at Post-treatment Week 12~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes (PRO) score and SVR12 status as covariates.p-value: 0.03595% CI: [-3.86, -0.14]ANCOVA
Comparison: F0-F1 vs F3 at Post-treatment Week 12~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.01595% CI: [-3.88, -0.42]ANCOVA
Comparison: F0-F1 vs F4 at Post-treatment Week 12p-value: 0.04895% CI: [-3.46, -0.01]ANCOVA
Comparison: F0-F1 vs F2 at Post-treatment Week 24~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.46695% CI: [-2.67, 1.22]ANCOVA
Comparison: F0-F1 vs F3 at Post-treatment Week 24~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.03595% CI: [-3.7, -0.13]ANCOVA
Comparison: F0-F1 vs F4 at Post-treatment Week 24~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.01595% CI: [-4.01, -0.43]ANCOVA
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.
Time frame: From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | 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 | At Post-treatment Week 12 | 2.7 units on a scale | Standard Deviation 9.77 |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | 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 | At Post-treatment Week 24 | 3.2 units on a scale | Standard Deviation 9.85 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | 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 | At Post-treatment Week 24 | 1.9 units on a scale | Standard Deviation 7.28 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | 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 | At Post-treatment Week 12 | 1.0 units on a scale | Standard Deviation 9.05 |
| Baseline Fibrosis Stage F3 | 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 | At Post-treatment Week 12 | 0.9 units on a scale | Standard Deviation 9.64 |
| Baseline Fibrosis Stage F3 | 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 | At Post-treatment Week 24 | 1.5 units on a scale | Standard Deviation 10.73 |
| Baseline Fibrosis Stage F4 | 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 | At Post-treatment Week 12 | 0.3 units on a scale | Standard Deviation 10.62 |
| Baseline Fibrosis Stage F4 | 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 | At Post-treatment Week 24 | 0.4 units on a scale | Standard Deviation 10.2 |
Comparison: F0-F1 vs F2 at Post-treatment Week 12~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.21695% CI: [-3.3, 0.75]ANCOVA
Comparison: F0-F1 vs F3 at Post-treatment Week 12~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.07495% CI: [-3.58, 0.17]ANCOVA
Comparison: F0-F1 vs F4 at Post-treatment Week 12~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.05695% CI: [-3.67, 0.05]ANCOVA
Comparison: F0-F1 vs F2 at Post-treatment Week 24~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.41195% CI: [-2.84, 1.16]ANCOVA
Comparison: F0-F1 vs F3 at Post-treatment Week 24~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.06595% CI: [-3.55, 0.11]ANCOVA
Comparison: F0-F1 vs F4 at Post-treatment Week 24p-value: 0.02695% CI: [-3.91, -0.25]ANCOVA
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.
Time frame: From Baseline to Post-Treatment Week 12 and Post-Treatment Week 24
Population: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | 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 | At Post-treatment Week 12 | 1.2 units on a scale | Standard Deviation 6.33 |
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | 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 | At Post-treatment Week 24 | 1.1 units on a scale | Standard Deviation 6.86 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | 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 | At Post-treatment Week 24 | 0.5 units on a scale | Standard Deviation 7.47 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | 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 | At Post-treatment Week 12 | 0.0 units on a scale | Standard Deviation 6.32 |
| Baseline Fibrosis Stage F3 | 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 | At Post-treatment Week 12 | 1.8 units on a scale | Standard Deviation 7.8 |
| Baseline Fibrosis Stage F3 | 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 | At Post-treatment Week 24 | 2.3 units on a scale | Standard Deviation 8.11 |
| Baseline Fibrosis Stage F4 | 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 | At Post-treatment Week 12 | 1.4 units on a scale | Standard Deviation 7.54 |
| Baseline Fibrosis Stage F4 | 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 | At Post-treatment Week 24 | 1.8 units on a scale | Standard Deviation 7.77 |
Comparison: F0-F1 vs F2 at Post-treatment Week 12~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.02695% CI: [-3.3, -0.21]ANCOVA
Comparison: F0-F1 vs F3 at Post-treatment Week 12~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.47295% CI: [-1.97, 0.91]ANCOVA
Comparison: F0-F1 vs F4 at Post-treatment Week 12~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.15995% CI: [-2.47, 0.4]ANCOVA
Comparison: F0-F1 vs F2 at Post-treatment Week 24~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.12595% CI: [-2.95, 0.36]ANCOVA
Comparison: F0-F1 vs F3 at Post-treatment Week 24~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.75695% CI: [-1.78, 1.29]ANCOVA
Comparison: F0-F1 vs F4 at Post-treatment Week 24~The difference between baseline fibrosis stage groups in mean change from baseline was analyzed using ANCOVA with baseline fibrosis stage (F0-F1, F2, F3 and F4) as a factor and baseline patient reported outcomes(PRO) score and SVR12 status as covariates.p-value: 0.31595% CI: [-2.32, 0.75]ANCOVA
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.
Time frame: 12 weeks after the last actual dose of study drug
Population: 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.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 95.3 percentage of participants |
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%.
Time frame: Up to Treatment Week 24
Population: Safety population: all participants enrolled in this study (M14-222; TOPAZ-II) who received at least one dose of study drug with available data
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Participants in Studies M14-222 and M14-423 Who Did Not Achieve SVR12 | Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets | 100.22 percentage of tablets taken | Standard Deviation 22.88 |
| Participants in Studies M14-222 and M14-423 Who Achieved SVR12 | Treatment Compliance: Percentage of Tablets Taken Relative to the Total Tablets | 99.86 percentage of tablets taken | Standard Deviation 12.4 |