Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as ABT-450
Technivie · 28 trials · 17 indications
SVR12 is defined as hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (LLOQ) at 12 weeks following therapy. 95% confidence interval (CI) is calculated using Wilson's score method. The lower bound of the 95% CI for the percentage of participants with SVR12 must exceed 67% to achieve superiority.
SVR24 is defined as HCV RNA less than the LLOQ at 24 weeks following therapy. 95% CI is calculated using Wilson's score method. The lower bound of the 95% CI for the percentage of participants with SVR12 must exceed 67% to achieve superiority. SVR24 is primary outcome measure only for China.
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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).
Time to liver-related death was defined as days from the 1st day of study drug dosing for the subject to date of liver-related death. All liver-related deaths were to be included, regardless of whether the death occurred while subject was still taking study drug or had previously discontinued study drug. If the subject didn't experience event of interest nor had died (all-cause death), their data was to be censored at date of last available assessment. For those with no post-baseline assessment, data was to be censored on 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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).
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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).
Time to liver transplantation was defined as days from 1st day of study drug dosing for subject to date of liver transplantation. All liver transplantation was to be included, whether it occurred while the subject was still taking study drug or had previously discontinued study drug. If the subject didn't experience event of interest nor had died (all-cause death), their data was to be censored at the date of their last available assessment. For those with no post-baseline assessment, data was to be censored on 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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).
Time to hepatocellular carcinoma (HCC) was defined as number of days from 1st day of study drug dosing for subject to date of hepatocellular carcinoma. All HCC was to be included, whether it occurred while subject was still taking study drug or had previously discontinued study drug. If the subject 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. 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 HCC. 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-I (this study) and the companion study TOPAZ-II (M14-222; NCT02167945).
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-II; NCT02167945.
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug.
The percentage noncirrhotic treatment-naïve participants who were eligible for IFN-based therapy and who had high viral load at baseline (HCV RNA ≥ 100,000 IU/mL) in the DB active treatment group with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of active study drug (SVR12). Among noncirrhotic treatment-naïve participants who were eligible for IFN-based therapy and who had high viral load at baseline, superiority of Arm A to a clinically relevant threshold based on historical SVR rate with telaprevir plus pegylated interferon alpha/ribavirin (pegIFN/RBV) in treatment-naïve, non-cirrhotic patients with high viral load; the lower bound of 95% confidence interval (LCB) had to exceed 63% to achieve superiority. The 95% confidence interval was calculated using the normal approximation to the binomial distribution.
Relapse is defined as a confirmed HCV ribonucleic acid (RNA) ≥ the lower limit of quantitation (LLOQ) at any time during the post-treatment period for a participant who had HCV RNA \< LLOQ at the end of treatment. Relapse12overall is defined as a confirmed HCV RNA ≥ LLOQ at any time after the sustained virologic response at Week 12 post-dosing (SVR12) assessment time point for a participant who achieved SVR12 and had post-SVR12 HCV RNA data available. SVR12 is defined as HCV RNA \< LLOQ in the SVR12 window (12 weeks after the last actual dose of study drug) without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. New HCV infection is defined as re-infection with a different HCV isolate.
The persistence of specific hepatitis C amino acid variants (treatment-emergent substitutions) associated with drug resistance in NS3, NS5A, or NS5B was evaluated in participants who had not achieved SVR12. Post-baseline time points were calculated relative to the last dose of study drug in the previous study.
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL.
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoints were noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1a infection treated with telaprevir and peginterferon(pegIFN)/RBV.
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug.
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoints were noninferiority of the percentage of participants who achieved sustained virologic response 12 weeks after treatment in each treatment arm (ABT-450/r/ABT-267 and ABT-333, plus either placebo RBV or RBV) compared with the historical control rate for noncirrhotic, treatment-naïve participants with HCV GT1b infection treated with telaprevir and peginterferon/RBV (pegIFN).
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\]) 12 weeks after the last dose of study drug.
SVR12 defined as hepatitis C (HCV) ribonucleic acid (RNA) less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.
SVR12 is defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) less than the lower limit of quantification (\< LLOQ) 12 weeks after the last dose of study drug without any confirmed quantifiable (≥ LLOQ) post-treatment value before or during that SVR window. The 95% confidence interval (CI) is calculated using the Wilson score method for binomial distribution. The primary efficacy endpoint was the non-inferiority of the percentage of participants in the GT1 Analysis Group in Part 2 achieving SVR12 compared to the historical SVR12 rate for sofosbuvir plus ribavirin (a non-inferiority threshold of the lower bound of the 95% CI of 74%).
SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than lower limit of quantitation \[LLOQ\] 12 weeks after the last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV).
The percentage of participants with sustained virologic response (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\<LLOQ\]) 12 weeks after the last dose of study drug.
The percentage of participants with SVR24 (plasma Hepatitis C virus ribonucleic acid \[HCV RNA\] level less than the lower limit of quantitation \[\< LLOQ\] 24 weeks after the last dose of study drug). The LLOQ for the assay was 25 IU/mL.
An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious adverse event (SAE) is an AE that results in death, is life-threatening, results in or prolongs hospitalization, results in congenital anomaly, persistent or significant disability/incapacity, spontaneous or elective abortion, or requires intervention to prevent a serious outcome. AEs were rated for severity as either Mild: transient and easily tolerated; Moderate: causes discomfort and interrupts usual activities; or Severe: causes considerable interference with usual activities, may be incapacitating or life-threatening. AEs related to study drug were assessed as being either probably or possibly related by the investigator. Treatment-emergent AEs (TEAEs) were collected from the first dose of study drug administration to 30 days after last dose; SAEs were collected from the time that informed consent was obtained to 30 days after last dose.
The percentage of participants achieving sustained virologic response 24 weeks after the last dose of study drug (SVR24), defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than the lower limit of quantitation (LLOQ), without any confirmed quantifiable (≥ LLOQ) post-treatment value before that time point. HCV RNA levels were measured from plasma by a central laboratory. The LLOQ for the assay was 25 IU/mL. The primary efficacy endpoint was the comparison between treatment-naïve participants following 8 weeks of treatment with 3 DAAs and ribavirin and those with 12 weeks of treatment with 3 DAAs and ribavirin (Group A versus Group G).
Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (\< 25 IU/mL). Participants with missing data were imputed as failures.
Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of detection (\< 15 IU/mL).
Analysis of the percentage of participants with hepatitis C virus ribonucleic acid less than the lower limit of quantitation (\< 25 IU/mL).
Plasma HCV RNA levels (reported as log10 IU/mL) were determined for each sample using a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) assay that had a lower limit of detection of 10 IU/mL and a lower limit of quantification of 25 IU/mL. The baseline value was the HCV RNA level before the first dose of study drug on Day 1. The maximal change during monotherapy was the difference from baseline to the lowest log10 HCV RNA level anytime after the first dose of study drug on Day 1 through the last log10 HCV RNA level before the first dose of study drug on Day 4. Data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-450 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of ABT-450 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-450 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-450 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-450 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ABT-450 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ritonavir using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of ritonavir was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ritonavir using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ritonavir was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ritonavir using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ritonavir was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-072 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of ABT-072 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-072 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-072 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-072 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC24 of ABT-072 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The maximum plasma concentration (Cmax; measured in ng/mL) is the highest concentration that a drug achieves in the blood after administration in a dosing interval. The Cmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours); 2, 4, 8, 12, and 16 hours after the morning dose on Day 1; and prior to dose on Day 2 (24 hours after Day 1 dose). The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The time to maximum plasma concentration (Tmax; measured in hours) is the time it takes for a drug to achieve Cmax. The Tmax of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Blood samples were collected immediately prior to morning dose (time 0 hours) and at 2, 4, 8, and 12 hours after the morning dose on Day 1. The samples were analyzed for the concentration of ABT-333 using validated analytical methods. The area under the plasma concentration-time curve (AUC; measured in ng\*hr/mL) is a method of measurement to determine the total exposure of a drug in blood plasma. The AUC12 of ABT-333 was estimated using non-compartmental methods and data are reported as the mean ± standard deviation.
Cmax is the highest concentration that a drug achieves in the blood after administration in a dosing interval.
Tmax is the time it takes for a drug to achieve Cmax.
Ctrough is the lowest concentration of a drug in the blood after administration in a dosing interval.
Ctrough is the lowest concentration of a drug in the blood after administration in a dosing interval.
Ctrough is the lowest concentration of a drug in the blood after administration in a dosing interval.
Ctrough is the lowest concentration of a drug in the blood after administration in a dosing interval.
dose normalized AUC(0-inf) for oral dose/dose normalized AUC(0-inf) for IV dose
| Arm | Type | Description |
|---|---|---|
| ABT-450/r/ABT-267 + ABT-333 + Ribavirin | EXPERIMENTAL | ABT-450/r/ABT-267 once daily + ABT-333 twice daily + weight-based RBV divided twice daily for 12 weeks |
| 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. |
| ABT-450/r/ABT-267 plus RBV for 12 weeks | EXPERIMENTAL | ABT-450/r/ABT-267 (150/100/25 mg once daily) plus weight-based ribavirin (RBV; 400 to 1,000 mg/day, divided twice daily) for 12 weeks |
| ABT-450/r/ABT-267 plus RBV for 16 weeks | EXPERIMENTAL | ABT-450/r/ABT-267 (150/100/25 mg once daily) plus weight-based RBV (400 to 1,000 mg/day, divided twice daily) for 16 weeks |
| Substudy 1, Arm A: DB 2-DAA | EXPERIMENTAL | Double-blind (DB) 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2 direct-acting antiviral agents \[2-DAA\]) once daily (QD) for 12 weeks in participants without cirrhosis |
| Substudy 1, Arm B: DB Placebo, Followed by OL 2-DAA | PLACEBO_COMPARATOR | DB placebo QD for 12 weeks followed by open-label (OL) 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants without cirrhosis |
| Substudy 2, Arm C: OL 2-DAA | EXPERIMENTAL | OL 150 mg ABT-450/100 mg ritonavir/25 mg ABT-267 (2-DAA) QD for 12 weeks in participants with compensated cirrhosis |
| All Participants | OTHER | Participants who received ABT-450, ABT-333 or ABT-267 at any dose level in an eligible prior AbbVie Phase 2 or 3 study for the treatment of chronic HCV, followed for up to 3 years post-treatment. |
| 3-DAA/RBV | EXPERIMENTAL | 3-DAA (ABT-450/r/ABT-267 \[150 mg/ 100 mg/ 25 mg once daily\] and ABT-333 \[250 mg twice daily\]) plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks. |
| TPV/RBV | ACTIVE_COMPARATOR | TPV (750 mg every 8 hours) coadministered with pegIFN (180 micrograms subcutaneously \[SC\] weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks, followed by pegIFN (180 micrograms SC weekly) and weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for either 12 or 36 weeks, per local prescribing information. |
| ABT-450/r/ABT-267 and ABT-333, Plus RBV | EXPERIMENTAL | ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| ABT-450/r/ABT-267 and ABT-333, Plus Placebo RBV | EXPERIMENTAL | ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks plus placebo RBV (twice daily) for 12 weeks |
| Arm A: 3-DAA + RBV in GT1a | EXPERIMENTAL | ABT-450/r/ABT-267 150 mg/100 mg/25 mg once daily (QD) and ABT-333 250 mg twice daily (BID) and weight-based RBV for 12 weeks (3 direct-acting antivirals \[DAAs\] with RBV in GT1a) |
| Arm B: TPV/PR in GT1a | ACTIVE_COMPARATOR | Telaprevir (TPV) 750 mg every 8 hours (q8h) and pegIFN 180 µg/week and weight-based RBV (PR) for 12 weeks followed by an additional 12 or 36 weeks of pegIFN and weight-based RBV according to response guided therapy per the prescribing information for telaprevir (telaprevir with pegIFN/RBV in GT1a) |
| Arm C: 3-DAA + RBV in GT1b | EXPERIMENTAL | ABT-450/r/ABT-267 150 mg/100 mg/25 mg QD and ABT-333 250 mg BID and weight-based RBV for 12 weeks (3 DAAs with RBV in GT1b) |
| Arm D: 3-DAA in GT1b | EXPERIMENTAL | ABT-450/r/ABT-267 150 mg/100 mg/25 mg QD and ABT-333 250 mg BID for 12 weeks (3 DAAs without RBV in GT1b) |
| Arm E: TPV/PR in GT1b | ACTIVE_COMPARATOR | Telaprevir 750 mg q8h and pegIFN 180 µg/week and weight-based RBV for 12 weeks followed by an additional 12 or 36 weeks of pegIFN and weight-based RBV according to response guided therapy per the prescribing information for telaprevir (telaprevir with pegIFN/RBV in GT1b) |
| Placebo Followed by ABT-450/r/ABT-267 and ABT-333, plus RBV | EXPERIMENTAL | Double-blind placebo for 12 weeks, followed by open-label ABT-450/r/ABT-267 (150 mg/100 mg/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based RBV (RBV; dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks |
| ABT-450/r/ABT-267 and ABT-333, plus RBV for 12 weeks | EXPERIMENTAL | ABT-450/r/ABT-267 (150/100/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; 1,000 mg/day if \<75 kg or 1,200 mg/day if ≥75 kg, divided twice daily) for 12 weeks |
| ABT-450/r/ABT-267 and ABT-333, plus RBV for 24 weeks | EXPERIMENTAL | ABT-450/r/ABT-267 (150/100/25 mg once daily) and ABT-333 (250 mg twice daily), plus weight-based ribavirin (RBV; 1,000 mg/day if \<75 kg or 1,200 mg/day if ≥75 kg, divided twice daily) for 24 weeks |
| ABT-450/r/ABT-267 and ABT-333 | EXPERIMENTAL | ABT-450/r/ABT-267 (150 mg/ 100 mg/ 25 mg once daily) and ABT-333 (250 mg twice daily) for 12 weeks |
| ABT-450/r and ABT-530 plus RBV | EXPERIMENTAL | ABT-450/r (150 mg/100 mg) once daily (QD) co-administered with ABT-530 (120 mg) once daily (QD) plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) for 12 weeks. |
| ARM A | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 coadministered with ribavirin (RBV) for 12 weeks for participants receiving atazanavir once-daily or raltegravir twice-daily |
| ARM B | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 24 weeks for participants receiving atazanavir once-daily or raltegravir twice-daily |
| ARM C | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for participants receiving darunavir once-daily |
| ARM D | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for participants receiving darunavir twice-daily |
| ARM E | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 for 12 weeks for noncirrhotic (at screening) GT1b-infected participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily |
| ARM F | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 for 12 weeks for cirrhotic (at screening) GT1b-infected sofosbuvir-naive participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily |
| ARM G | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for cirrhotic (at screening) GT1b-infected sofosbuvir-naive participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily |
| ARM H | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for cirrhotic (at screening) GT1b-infected sofosbuvir-experienced participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily |
| ARM I | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 12 weeks for noncirrhotic (at screening) GT1a-infected participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily |
| ARM J | EXPERIMENTAL | ABT-450/r/ABT-267 and ABT-333 coadministered with RBV for 24 weeks for cirrhotic (at screening) GT1a-infected participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily |
| ARM K | EXPERIMENTAL | ABT-450/r/ABT-267 coadministered with RBV for 12 weeks for participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily, dolutegravir once-daily or twice-daily, darunavir once-daily |
| ARM L | EXPERIMENTAL | ABT-450/r/ABT-267 coadministered with RBV for 24 weeks for participants receiving any of the following: atazanavir once-daily, raltegravir twice-daily, dolutegravir once-daily or twice-daily, darunavir once-daily |
| 2-DAA + PegIFN/RBV | EXPERIMENTAL | 2-direct-acting antiviral (2-DAA: ABT-450 \[paritaprevir\] 200 mg once daily \[QD\], ritonavir 100 mg QD, ABT-267 \[ombitasvir\] 25 mg QD) plus pegylated interferon alpha-2a (pegIFN) 180 mcg once weekly and Ribavirin (RBV) weight-based dosing, 1000 to 1200 mg divided twice daily (BID) for 24 weeks (Substudy 1) and followed by pegIFN and RBV alone for an additional 24 weeks (Substudy 2). |
| Group 1 | EXPERIMENTAL | ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants |
| Group 2 | EXPERIMENTAL | ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-naïve HCV GT1b-infected participants |
| Group 3 | EXPERIMENTAL | ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, HCV GT1b-infected, pegylated-interferon/ribavirin (pegIFN/RBV) treatment null responder participants |
| Group 4 | EXPERIMENTAL | ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if \< 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, treatment-naïve, HCV GT4-infected participants |
| Group 5 | EXPERIMENTAL | ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 12 weeks to adult noncirrhotic, treatment-experienced, HCV GT4-infected participants |
| Group 6 | EXPERIMENTAL | ABT-450 150 mg/ r 100 mg, ABT-267 25 mg , once daily and weight-based ribavirin (RBV; 1,000 mg/day if \< 75 kg or 1,200 mg/day if ≥ 75 kg, divided twice daily) for 12 weeks to adult noncirrhotic, HCV GT4-infected, pegylated-interferon/RBV (pegIFN/RBV) treatment-experienced participants |
| Group 7 | EXPERIMENTAL | ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, treatment-naïve participants with compensated cirrhosis |
| Group 8 | EXPERIMENTAL | ABT-450 150 mg/ r 100 mg, and ABT-267 25 mg once daily for 24 weeks to adult, HCV GT1b-infected, pegylated-interferon/RBV(pegIFN/RBV) treatment-experienced participants with compensated cirrhosis |
| Arm 1 | EXPERIMENTAL | Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. |
| Arm 2 | EXPERIMENTAL | Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. |
| Arm 3 | EXPERIMENTAL | Participants with HCV GT1b received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 24 weeks. |
| Arm 4 | EXPERIMENTAL | Participants with HCV GT1b received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 24 weeks. |
| Arm 5 | EXPERIMENTAL | Participants with HCV GT2 received ABT-450/ritonavir (100/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. |
| Arm 6 | EXPERIMENTAL | Participants with HCV GT2 received ABT-450/ritonavir (150/100 mg) and ABT-267 (25 mg) once daily for 12 weeks. |
| Group A | EXPERIMENTAL | Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 8 weeks. |
| Group B | EXPERIMENTAL | Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks. |
| Group C | EXPERIMENTAL | Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks. |
| Group D | EXPERIMENTAL | Treatment-naïve participants received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily for 12 weeks. |
| Group E | EXPERIMENTAL | Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ABT-333 400 mg twice daily for 12 weeks. |
| Group F | EXPERIMENTAL | Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily for 12 weeks. |
| Group G | EXPERIMENTAL | Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks. |
| Group H | EXPERIMENTAL | Treatment-naïve participants received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks. |
| Group I | EXPERIMENTAL | Treatment-naïve participants received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks. |
| Group J | EXPERIMENTAL | Participants who were null-responders to previous HCV treatment received ABT-450 200 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, and ribavirin dosed by weight, twice daily, for 12 weeks. |
| Group K | EXPERIMENTAL | Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks. |
| Group L | EXPERIMENTAL | Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 12 weeks. |
| Group M | EXPERIMENTAL | Participants who were null-responders to previous HCV treatment received ABT-450 100 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks. |
| Group N | EXPERIMENTAL | Participants who were null-responders to previous HCV treatment received ABT-450 150 mg and ritonavir 100 mg once daily, ABT-267 25 mg once daily, ABT-333 400 mg twice daily, and ribavirin dosed by weight, twice daily, for 24 weeks. |
| ABT-450/r and ABT-267 plus RBV in genotype 1 participants | EXPERIMENTAL | ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided twice daily (BID) in treatment-naïve participants with HCV genotype 1 infection. |
| ABT-450/r and ABT-267 plus RBV in genotype 2 participants | EXPERIMENTAL | ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 2 infection. |
| ABT-450/r and ABT-267 plus RBV in genotype 3 participants | EXPERIMENTAL | ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD plus weight-based ribavirin (RBV) divided BID in treatment-naïve participants with HCV genotype 3 infection. |
| ABT-450/r and ABT-267 in genotype 1 participants | EXPERIMENTAL | ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 1 infection. |
| ABT-450/r and ABT-267 in genotype 2 participants | EXPERIMENTAL | ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 2 infection. |
| ABT-450/r and ABT-267 in genotype 3 participants | EXPERIMENTAL | ABT-450/r (200/100 mg) once daily (QD) and ABT-267 (25 mg) QD in treatment-naïve participants with HCV genotype 3 infection. |
| ABT-450/r (250/100 mg) and ABT-333 plus RBV in treatment-naïve | EXPERIMENTAL | ABT-450/r (250/100 mg) once daily (QD) and ABT-333 (400 mg) twice daily (BID) plus weight-based ribavirin (RBV) divided BID for 12 weeks in treatment-naïve participants. |
| ABT-450/r (150/100 mg) and ABT-333 plus RBV in treatment-naïve | EXPERIMENTAL | ABT-450/r (150/100 mg) once daily (QD) and ABT-333 (400 mg) twice daily (BID) plus weight-based ribavirin (RBV) divided BID for 12 weeks in treatment-naïve participants. |
| ABT-450/r (150/100 mg) and ABT-333 plus RBV in non-responders | EXPERIMENTAL | ABT-450/r (150/100 mg) once daily (QD) and ABT-333 (400 mg) twice daily (BID) plus weight-based ribavirin (RBV) divided BID in previous non-responders to pegylated interferon (pegIFN) and RBV. |
| ABT-450/r and ABT-072, plus ribavirin (RBV) | EXPERIMENTAL | ABT-450/r (150/100 mg) once daily (QD) and ABT-072 (400 mg) QD plus weight-based RBV divided twice daily (BID) for 12 weeks. |
| ABT-450/r (50/100 mg) once daily (QD) + pegIFN/RBV | EXPERIMENTAL | Participants received 50 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-450/r (100/100 mg) once daily (QD) + pegIFN/RBV | EXPERIMENTAL | Participants received 100 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-450/r (200/100 mg) once daily (QD) + pegIFN/RBV | EXPERIMENTAL | Participants received 200 mg ABT-450 and 100 mg ritonavir (r) monotherapy once daily for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-072 (100 mg) once daily (QD) + pegIFN/RBV | EXPERIMENTAL | Participants received 100 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-072 (300 mg) once daily (QD) + pegIFN/RBV | EXPERIMENTAL | Participants received 300 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-072 (600 mg) once daily (QD) + pegIFN/RBV | EXPERIMENTAL | Participants received 600 mg ABT-072 monotherapy once daily for 3 days followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-333 (400 mg) twice a day (BID) + pegIFN/RBV | EXPERIMENTAL | Participants received 400 mg ABT-333 monotherapy twice a day for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-333 (800 mg) twice daily (BID) + pegIFN/RBV | EXPERIMENTAL | Participants received 800 mg ABT-333 monotherapy twice a day for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| Placebo + pegIFN/RBV | PLACEBO_COMPARATOR | Participants received matching placebo for ABT-450/r, ABT-072, or ABT-333 monotherapy at each dose level for 3 days, followed by the addition of pegylated interferon/ribavirin (pegIFN/RBV) for a total of 12 weeks of combination treatment, followed by 36 weeks of pegIFN/RBV alone. Pegylated interferon was dosed at 180 µg subcutaneously once a week and RBV was dosed 1000 or 1200 mg daily divided twice a day. |
| ABT-450/r/ABT-267 + ABT-333 | EXPERIMENTAL | ABT-450/r/ABT-267 will be administered once daily in the morning and ABT-333 will be administered in the morning and evening for 14 days. |
| Group 1 - Regimen A | EXPERIMENTAL | 8 Subjects in Group I - Regimen A: ABT-450/r/ABT-267 |
| Group 2 - Regimen B | EXPERIMENTAL | 8 Subjects in Group II - Regimen B: ABT-450/r/ABT-267 |
| 1 | ACTIVE_COMPARATOR | ABT-450 |
| 2 | PLACEBO_COMPARATOR | Placebo for ABT-450 |
| 3 | ACTIVE_COMPARATOR | ABT-450/ritonavir |
| 4 | PLACEBO_COMPARATOR | Placebo for ABT-450/placebo for ritonavir |
| Name | Type | Description |
|---|---|---|
| ABT-450/r/ABT-267 | DRUG | Tablet |
| ABT-333 | DRUG | Tablet |
| ribavirin | DRUG | Tablet |
| 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. |
| Placebo | DRUG | Tablet |
| ABT-450/ritonavir | DRUG | ABT-450 coformulated with ritonavir. Drug is not administered -- this study is follow-up for participants previously receiving the drug. |
| ABT-267 | DRUG | Drug is not administered -- this study is follow-up for participants previously receiving the drug. |
| ABT-450/r/ABT-267, ABT-333 | DRUG | Tablet; ABT-450 coformulated with ritonavir and ABT-267, ABT-333 tablet |
| Pegylated Interferon a-2a (PegINF) | DRUG | Pre-filled syringe |
| Telaprevir | DRUG | Film-coated tablet |
| Placebo for Ribavirin | DRUG | Capsule |
| Pegylated Interferon alpha 2-a (PegIFN) | DRUG | Pre-filled syringe |
| Placebo for ABT-450/r/ABT-267 | DRUG | Tablet |
| Placebo for ABT-333 | DRUG | Tablet |
| ABT-450/ritonavir (r) | DRUG | Tablet |
| ABT-530 | DRUG | Tablet |
| ABT-450/r | DRUG | ABT-450 (tablets) dosed with ritonavir (capsules or tablets) |
| pegylated interferon alpha-2a (pegIFN) | DRUG | pegIFN alpha-2a (syringe) |
| ABT-450/ritonavir, ABT-267 | DRUG | ABT-450 (tablet) dosed with ritonavir (capsule), and ABT-267 (tablet) |
| ABT-450 | DRUG | ABT-450 tablets |
| Ritonavir | DRUG | Ritonavir capsules |
| ABT-072 | DRUG | tablets |
| Peginterferon alpha-2a | DRUG | Syringe, 180 µg/0.5 mL for subcutaneous injections |
| placebo for ABT-450 | DRUG | capsules, QD, one dose |
| Placebo for ritonavir | DRUG | capsules, QD, one dose |
Inclusion Criteria: 1. Chinese, South Korean, and Taiwanese descent with full Chinese, South Korean, and Taiwanese parentage. 2. Chronic HCV-infection prior to study enrollment. 3. Screening laboratory result indicating HCV genotype 1b-infection. 4. Compensated cirrhosis defined as a Child-Pugh Sco...
Technivie is an investigational small molecule therapy studied for chronic hepatitis C virus infection, including genotype 1 HCV and chronic HCV infection in adults. Clinical development has focused on HCV infection, including patients with compensated cirrhosis, and on absolute bioavailability assessments.
Technivie is being developed by AbbVie Inc., which trades under the ticker ABBV. AbbVie sponsored the clinical program evaluating the combination of ABT-450/ritonavir, ABT-267, and ABT-333 in chronic hepatitis C virus infection.
Technivie is in Phase 1 development. Twelve clinical trials have been completed and none are currently active, with a total enrollment of 3,343 participants across the program. The studies include Phase 1 pharmacokinetic work and Phase 3 HCV trials.
Completed trials include NCT02534870, a Phase 1 pharmacokinetic and safety study in healthy Chinese subjects; NCT02517528, a Phase 3 study in Asian adults with genotype 1b HCV and compensated cirrhosis; and NCT02219490 and NCT02167945, Phase 3 long-term outcome studies in genotype 1 HCV.
Technivie is an investigational therapy and remains in clinical development. The program's 12 trials are all completed, with no active studies, and the completed work includes Phase 1 and Phase 3 evaluations in chronic hepatitis C virus infection.