A Randomized Study to Evaluate the Safety, Tolerability and Antiviral Activity of ABT-450, ABT-333 and ABT-072 (Champion2)

A Blinded, Randomized, Placebo-controlled, Dose Ranging Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antiviral Activity of Multiple Doses of ABT-450 With Ritonavir (ABT-450/r), ABT-333 or ABT-072 Each Administered Alone and in Combination With Peginterferon α-2a and Ribavirin (PegIFN/RBV) in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C Virus (HCV) Infection

This study assessed the safety, tolerability, pharmacokinetics, and antiviral activity of multiple oral doses of ABT-450/ritonavir (r), ABT-333 (also known as dasabuvir), or ABT-072 in hepatitis C virus (HCV), genotype 1-infected, treatment-naïve adults.

Study Overview

• Status: Completed
• Conditions: Hepatitis C; Chronic Hepatitis C Infection; HCV; Hepatitis C Genotype 1
• Intervention / Treatment: Drug: ABT-450; Drug: Ritonavir; Drug: Peginterferon alpha-2a; Drug: Ribavirin; Drug: ABT-072; Drug: ABT-333; Other: Placebo

Detailed Description

This was a Phase 2a, randomized, blinded, placebo-controlled, dose-ranging study in chronically, hepatitis C virus (HCV) genotype 1-infected participants designed to explore the safety, tolerability, pharmacokinetics, antiviral activity, as well as the evolution and persistence to resistance of ABT-450/r, ABT-333, or ABT-072. Participants were treated with ABT-450/r, ABT-333, or ABT-072 monotherapy for 3 days, followed by 81 days (12 weeks minus 3 days of monotherapy) of ABT-450/r, ABT-333, or ABT-072 combined with pegylated interferon/ribavirin (pegIFN/RBV), followed by 36 weeks of pegIFN/RBV alone. Participants randomized to an ABT-450/r treatment group who achieved rapid virologic response (RVR) and had HCV ribonucleic acid (RNA) levels < 25 IU/mL at all subsequent visits were eligible to stop pegIFN/RBV therapy on or after Week 24.

• Study Type: Interventional
• Enrollment (Actual): 74
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • Ponce, Puerto Rico, 00731
    • Site Reference ID/Investigator# 23363
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Site Reference ID/Investigator# 23392
  • California
    • Anaheim, California, United States, 92801
      • Site Reference ID/Investigator# 23370
    • La Jolla, California, United States, 92037
      • Site Reference ID/Investigator# 23387
    • Los Angeles, California, United States, 90048
      • Site Reference ID/Investigator# 23388
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Site Reference ID/Investigator# 23371
  • Florida
    • Orlando, Florida, United States, 32803
      • Site Reference ID/Investigator# 23369
    • Orlando, Florida, United States, 32809
      • Site Reference ID/Investigator# 26362
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Site Reference ID/Investigator# 23373
    • Chicago, Illinois, United States, 60612
      • Site Reference ID/Investigator# 24908
  • Indiana
    • Indianapolis, Indiana, United States, 46202-5121
      • Site Reference ID/Investigator# 23381
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70810
      • Site Reference ID/Investigator# 23372
    • New Orleans, Louisiana, United States, 70112
      • Site Reference ID/Investigator# 24710
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Site Reference ID/Investigator# 23391
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Site Reference ID/Investigator# 23377
  • Minnesota
    • St. Paul, Minnesota, United States, 55114
      • Site Reference ID/Investigator# 24909
  • New York
    • New York, New York, United States, 10016
      • Site Reference ID/Investigator# 35842
    • New York, New York, United States, 10021
      • Site Reference ID/Investigator# 23379
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7584
      • Site Reference ID/Investigator# 23375
    • Durham, North Carolina, United States, 27705
      • Site Reference ID/Investigator# 23385
  • Texas
    • Dallas, Texas, United States, 75203
      • Site Reference ID/Investigator# 23376
    • Houston, Texas, United States, 77030
      • Site Reference ID/Investigator# 24891
    • San Antonio, Texas, United States, 78215
      • Site Reference ID/Investigator# 23382
  • Utah
    • Salt Lake City, Utah, United States, 84132-2410
      • Site Reference ID/Investigator# 24715
  • Washington
    • Seattle, Washington, United States, 98101
      • Site Reference ID/Investigator# 25463
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Site Reference ID/Investigator# 23383

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Chronic hepatitis C virus (HCV), genotype 1 infection (HCV ribonucleic acid level greater than or equal to 100,000 IU/mL) at screening
• Liver biopsy within 3 years with histology consistent with HCV-induced liver damage, with no evidence of cirrhosis or liver pathology due to any cause other than chronic HCV
• Treatment naïve male or female between the ages of 18 and 65
• Females must be post-menopausal for more than 2 years or surgically sterile
• Negative screen for drugs and alcohol
• Negative hepatitis B surface antigen (HBsAg) and anti-human immunodeficiency virus antibodies (anti-HIV Ab)
• No use of cytochrome P450 3A (CYP3A) and cytochrome P450 2C8 (CYP2C8) enzyme inducers or inhibitors within 1 month of dosing
• Be in a condition of general good health, as perceived by the investigator, other than HCV infection

Exclusion Criteria:

• Significant sensitivity to any drug
• Use of herbal supplements within 2 weeks prior to study drug dosing
• History of major depression within 2 years
• Prior treatment with any investigational or commercially available anti-HCV agents
• Abnormal laboratory tests

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ABT-450/r (50/100 mg) once daily (QD) + pegIFN/RBV; 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.	Drug: ABT-450; 50 mg capsules co-administered with ritonavir; Drug: Ritonavir; 100 mg capsules co-administered with ABT-450; Other Names: Norvir; ABT-538; Drug: Peginterferon alpha-2a; Syringe, 180 µg/0.5 mL for subcutaneous injections; Drug: Ribavirin; 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: ABT-450/r (100/100 mg) once daily (QD) + pegIFN/RBV; 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.	Drug: ABT-450; 50 mg capsules co-administered with ritonavir; Drug: Ritonavir; 100 mg capsules co-administered with ABT-450; Other Names: Norvir; ABT-538; Drug: Peginterferon alpha-2a; Syringe, 180 µg/0.5 mL for subcutaneous injections; Drug: Ribavirin; 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: ABT-450/r (200/100 mg) once daily (QD) + pegIFN/RBV; 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.	Drug: ABT-450; 50 mg capsules co-administered with ritonavir; Drug: Ritonavir; 100 mg capsules co-administered with ABT-450; Other Names: Norvir; ABT-538; Drug: Peginterferon alpha-2a; Syringe, 180 µg/0.5 mL for subcutaneous injections; Drug: Ribavirin; 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day
Experimental: ABT-072 (100 mg) once daily (QD) + pegIFN/RBV; 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.	Drug: Peginterferon alpha-2a; Syringe, 180 µg/0.5 mL for subcutaneous injections; Drug: Ribavirin; 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day; Drug: ABT-072; 50 mg tablet
Experimental: ABT-072 (300 mg) once daily (QD) + pegIFN/RBV; 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.	Drug: Peginterferon alpha-2a; Syringe, 180 µg/0.5 mL for subcutaneous injections; Drug: Ribavirin; 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day; Drug: ABT-072; 50 mg tablet
Experimental: ABT-072 (600 mg) once daily (QD) + pegIFN/RBV; 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.	Drug: Peginterferon alpha-2a; Syringe, 180 µg/0.5 mL for subcutaneous injections; Drug: Ribavirin; 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day; Drug: ABT-072; 50 mg tablet
Experimental: ABT-333 (400 mg) twice a day (BID) + pegIFN/RBV; 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.	Drug: Peginterferon alpha-2a; Syringe, 180 µg/0.5 mL for subcutaneous injections; Drug: Ribavirin; 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day; Drug: ABT-333; 400 mg tablet; Other Names: Dasabuvir
Experimental: ABT-333 (800 mg) twice daily (BID) + pegIFN/RBV; 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.	Drug: Peginterferon alpha-2a; Syringe, 180 µg/0.5 mL for subcutaneous injections; Drug: Ribavirin; 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day; Drug: ABT-333; 400 mg tablet; Other Names: Dasabuvir
Placebo Comparator: Placebo + pegIFN/RBV; 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.	Drug: Peginterferon alpha-2a; Syringe, 180 µg/0.5 mL for subcutaneous injections; Drug: Ribavirin; 200 mg tablet dosed at 1000 or 1200 mg daily divided twice a day; Other: Placebo; Matching placebo for ABT-450/r, ABT-072, or ABT-333 monotherapy at each dose level

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal Change From Baseline in Hepatitis C Virus Ribonucleic Acid (HCV RNA) Levels During ABT-450/r, ABT-333, or ABT-072 Monotherapy Treatment	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.	Prior to dosing on Day 1 to before the morning dose on Day 4
Maximum Plasma Concentration (Cmax) of ABT-450	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.	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)
Time to Maximum Plasma Concentration (Tmax) of ABT-450	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.	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)
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-450	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.	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)
Maximum Plasma Concentration (Cmax) of Ritonavir	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.	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)
Time to Maximum Plasma Concentration (Tmax) of Ritonavir	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.	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)
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of Ritonavir	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.	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)
Maximum Plasma Concentration (Cmax) of ABT-072	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.	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)
Time to Maximum Plasma Concentration (Tmax) of ABT-072	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.	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)
Area Under the Plasma Concentration-time Curve From 0 to 24 Hours (AUC24) Post-dose of ABT-072	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.	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)
Maximum Plasma Concentration (Cmax) of ABT-333	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.	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)
Time to Maximum Plasma Concentration (Tmax) of ABT-333	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.	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)
Area Under the Plasma Concentration-time Curve From 0 to 12 Hours (AUC12) Post-dose of ABT-333	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.	Immediately prior to morning dose (time 0 hours) and at 2, 4, 8, and 12 hours after the morning dose on Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Rapid Virologic Response (RVR) at Week 4	Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels 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 (LLOQ) of 25 IU/mL. Rapid virologic response was defined as HCV RNA level < LLOQ (< 25 IU/mL) at Week 4. Data are reported as the percentage of participants with RVR.	Week 4
Percentage of Participants With Partial Early Virologic Response (EVR) at Week 12	Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels 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. Partial early virologic response (EVR) was defined as HCV RNA levels that decreased > 2 log10 IU/mL at Week 12 as compared to baseline. The baseline value was the last measurement before the first dose on Day 1. Data are reported as the percentage of participants with partial EVR.	Baseline and Week 12
Percentage of Participants With Complete Early Virologic Response (cEVR) at Week 12	Plasma hepatitis C virus ribonucleic acid (HCV RNA) levels 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 (LLOQ) of 25 IU/mL. Complete EVR was defined as HCV RNA levels < LLOQ (< 25 IU/mL) at Week 12. Data are reported as the percentage of participants with cEVR.	Week 12

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-450 in Non-structural Viral Protein 3 (NS3)	Baseline samples were analyzed for resistance-associated amino acid variants using population and clonal sequencing and were compared with the appropriate reference sequence (1a-H77 or 1b-Con1). Phenotypic resistance to ABT-450 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Available samples at Day 4 with HCV RNA ≥ 1000 IU/mL were analyzed for resistance-associated variants using population and clonal sequencing and were compared with the baseline sequences to assess amino acid changes. Phenotypic resistance to ABT-450 at Day 4 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance are presented.	Baseline and Day 4
Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-072 in Non-structural Viral Protein 5B (NS5B)	Baseline samples were analyzed for resistance-associated amino acid variants using population and clonal sequencing and were compared with the appropriate reference sequence (1a-H77 or 1b-Con1). Phenotypic resistance to ABT-072 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Available samples at Day 4 with HCV RNA ≥ 1000 IU/mL were analyzed for the presence of resistance-associated variants using population and clonal sequencing and were compared with the baseline sequences to assess amino acid changes. Phenotypic resistance to ABT-072 at Day 4 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance are presented.	Baseline and Day 4
Number of Participants With Resistance-Associated Variants and Phenotypic Resistance to ABT-333 in Non-structural Viral Protein 5B (NS5B)	Baseline samples were analyzed for resistance-associated amino acid variants using population and clonal sequencing and were compared with the appropriate reference sequence (1a-H77 or 1b-Con1). Phenotypic resistance to ABT-333 at baseline was assessed by calculating the fold difference in the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Available samples at Day 4 with HCV RNA ≥ 1000 IU/mL were analyzed for the presence of resistance-associated variants using population and clonal sequencing and were compared with the baseline sequences to assess amino acid changes. Phenotypic resistance to ABT-333 at Day 4 was assessed by calculating the fold difference in the EC50 compared with the EC50 for the corresponding baseline sample. The number of participants with variants at resistance-associated amino acid positions and phenotypic resistance are presented.	Baseline and Day 4
Change From Baseline in Hepatitis C Virus Patient-reported Outcomes (HCV-PRO) Total Score	The Hepatitis C Virus Patient-report Outcomes (HCV-PRO, formerly known as HCV Quality of Life) survey was used to assess disease-specific function and well-being on a scale from 0 to 100; a higher score indicated relatively good function and well-being of treated participants. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are reported as the group mean change from baseline ± standard deviation.	Baseline up to Post-treatment Week 24
Change From Baseline in ED-5D Visual Analog Scale (ED-5D VAS) Score	The ED-5D VAS was a self-rating survey used to capture the current health status of a participant and ranged from 0 (the worst imaginable health state) to 100 (best imaginable health state). Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation.	Baseline and Post-treatment Week 24
Change From Baseline in EQ-5D (3 Level) Health Index Score	The EQ-5D was a health state questionnaire used to measure five health dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). The combination of responses from all five dimensions were derived into an index score ranging from 0 to 1; a higher score indicated a more preferable health utility value from the societal perspectives. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation.	Baseline and Post-treatment Week 24
Change From Baseline in SF-36 Physical Component Summary (PCS)	The Physical Component Summary (PCS) of the SF-36 was used to measure the overall physical health status of a participant. The aggregated score of the SF-36 PCS score was standardized using a linear T-score transformation with a mean of 50 and a standard deviation of 10; a higher score indicated better physical function and well-being. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation.	Baseline and Post-treatment Week 24
Change From Baseline in SF-36 Mental Component Summary (MCS)	The Mental Component Summary (MCS) of the SF-36 was used to measure the overall mental health status of participants. The aggregated score of the SF-36 MPS was standardized using a linear T-score transformation with a mean of 50 and a standard deviation of 10; a higher score indicated better mental function and well-being. Data presented are the summaries across all participants, for each treatment arm, regardless of dose. Data are presented as the group mean change from baseline ± standard deviation.	Baseline and Post-treatment Week 24

Collaborators and Investigators

• Sponsor: AbbVie (prior sponsor, Abbott)
• Investigators: Study Director: Daniel Cohen, AbbVie

Publications and helpful links

General Publications

• Pilot-Matias T, Tripathi R, Cohen D, Gaultier I, Dekhtyar T, Lu L, Reisch T, Irvin M, Hopkins T, Pithawalla R, Middleton T, Ng T, McDaniel K, Or YS, Menon R, Kempf D, Molla A, Collins C. In vitro and in vivo antiviral activity and resistance profile of the hepatitis C virus NS3/4A protease inhibitor ABT-450. Antimicrob Agents Chemother. 2015 Feb;59(2):988-97. doi: 10.1128/AAC.04227-14. Epub 2014 Dec 1.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): January 1, 2012

Study Registration Dates

• First Submitted: February 22, 2010
• First Submitted That Met QC Criteria: February 22, 2010
• First Posted (Estimate): February 24, 2010

Study Record Updates

• Last Update Posted (Estimate): January 8, 2015
• Last Update Submitted That Met QC Criteria: December 29, 2014
• Last Verified: December 1, 2014

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Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Infections; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Ribavirin; Peginterferon alfa-2a; Ritonavir
• Other Study ID Numbers: M11-602