Back to resultsStudy to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
Primary Purpose
Chronic Hepatitis C Infection
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
ABT-267
ABT-450
ABT-333
Ritonavir
Ribavirin
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Hepatitis C Infection focused on measuring Hepatitis C,Genotype 1
Eligibility Criteria
Inclusion Criteria:
- Male or female between the age of 18 and 70 years, inclusive, at time of enrollment.
- Subject has never received antiviral treatment for hepatitis C virus (HCV) infection.
- Body mass index (BMI) is ≥ 18 to < 38 kg/m^2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
- Chronic HCV genotype 1-infection for at least 6 months prior to study enrollment.
- Subject has plasma HCV RNA level > 10,000 IU/mL at screening
Exclusion Criteria:
- History of severe, life-threatening or other significant sensitivity to any drug.
- Females who are or plan to become pregnant or breastfeeding or males whose partner is pregnant or planning to become pregnant.
- Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
- Positive test result for hepatitis B surface antigen or anti-human immunodeficiency virus (HIV) antibodies.
- Any current or past clinical evidence of cirrhosis (e.g., ascites, esophageal varices), or a liver biopsy or FibroTest/aspartate aminotransferase to platelet ratio (APRI) or FibroScan® showing cirrhosis or extensive bridging fibrosis.
Sites / Locations
- Site Reference ID/Investigator# 68002
- Site Reference ID/Investigator# 67383
- Site Reference ID/Investigator# 67382
- Site Reference ID/Investigator# 67385
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Experimental
Arm Label
ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV
ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV
Arm Description
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
Outcomes
Primary Outcome Measures
Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was estimated using noncompartmental analyses.
Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Time of maximum plasma concentration (Tmax; measured in hours) was estimated using noncompartmental analyses.
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC[24]; measured in ng multiplied by hour/mL) was estimated using noncompartmental analyses.
Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3
Blood samples were collected pre-dose on Day 2 (prior to second dose of ABT-267 monotherapy) and pre-dose on Day 3 (prior to first dose of combination therapy). The samples were analyzed for ABT-267 using validated analytical methods. Pre-dose plasma concentrations on Day 2 and Day 3 (Ctrough, measured in ng/mL) are reported.
Number of Participants With Adverse Events (AEs)
An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment.
The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs), and rated the severity of each event as either: Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening.
A serious adverse event was any event that resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention.
Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy
The baseline value was the last measurement before the first dose of ABT-267 monotherapy (Day 1). The maximal decrease during monotherapy was the change from baseline to the lowest log10 IU/mL HCV RNA level any time from the first dose of ABT-267 on Day 1 to the last log10 HCV RNA level before the first dose of ABT-267 combination therapy (Study Day 3).
Secondary Outcome Measures
Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy
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 and 24 weeks after the last dose of combination study drug. The LLOQ for the assay was 25 IU/mL.
Percentage of Participants With Rapid Virologic Response
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) after 4 weeks of combination therapy.
Percentage of Participants With End-of-Treatment Response
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) at the end of combination therapy (12 weeks).
Percentage of Participants With Extended Rapid Virologic Response
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) at Weeks 4 through 12 of combination therapy.
Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy
The relationship between ABT-267 dose, ABT-267 concentration, and response was analyzed as the change in viral load (measured as log10 IU/mL) from baseline (pre-dose on Day 1) to pre-dose on Days 2 and 3. Plasma concentrations of ABT-267 pre-dose on Days 2 and 3 are presented above in 4. Primary Outcome: Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3.
Full Information
NCT ID
NCT01563536
First Posted
January 27, 2012
Last Updated
June 1, 2018
Sponsor
AbbVie (prior sponsor, Abbott)
1. Study Identification
Unique Protocol Identification Number
NCT01563536
Brief Title
Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
Official Title
An Open-Label, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
Study Type
Interventional
2. Study Status
Record Verification Date
December 2014
Overall Recruitment Status
Completed
Study Start Date
February 2012 (undefined)
Primary Completion Date
April 2012 (Actual)
Study Completion Date
June 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
AbbVie (prior sponsor, Abbott)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to assess the safety, tolerability, pharmacokinetics, and antiviral activity of multiple, ascending doses of ABT-267 (also known as ombitasvir) administered as two-day monotherapy followed by ABT-267 in combination therapy with other direct-acting antiviral agents (DAAs) ABT-450 with ritonavir (ABT-450/r) and ABT-333 (also known as dasabuvir) plus ribavirin (RBV) in patients with chronic Hepatitis C virus (HCV) infection without cirrhosis.
Detailed Description
An open-label, multicenter study to evaluate the safety, tolerability, pharmacokinetics, and antiviral activity of ABT-267 as monotherapy for 2 days, followed by ABT-267, ABT-450 with ritonavir (ABT-450/r) and ABT-333 plus ribavirin (RBV) combination therapy for 12 weeks in treatment-naïve, non-cirrhotic patients with chronic hepatitis C virus (HCV) infection. The study included post-treatment follow-up for 48 weeks.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis C Infection
Keywords
Hepatitis C,Genotype 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV
Arm Type
Experimental
Arm Description
ABT-267 (1.5 mg once daily) as monotherapy for 2 days, then ABT-267 (1.5 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
Arm Title
ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV
Arm Type
Experimental
Arm Description
ABT-267 (25 mg once daily) as monotherapy for 2 days, then ABT-267 (25 mg once daily), ABT-450/r (150 mg/ 100 mg once daily) and ABT-333 (400 mg twice daily), plus weight-based RBV (dosed 1,000 or 1,200 mg daily divided twice a day) combination therapy for 12 weeks
Intervention Type
Drug
Intervention Name(s)
ABT-267
Other Intervention Name(s)
ombitasvir
Intervention Description
Tablet
Intervention Type
Drug
Intervention Name(s)
ABT-450
Intervention Description
Tablet
Intervention Type
Drug
Intervention Name(s)
ABT-333
Other Intervention Name(s)
dasabuvir
Intervention Description
Tablet
Intervention Type
Drug
Intervention Name(s)
Ritonavir
Intervention Description
Capsule
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Intervention Description
Tablet
Primary Outcome Measure Information:
Title
Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1
Description
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Maximum plasma concentration (Cmax; measured in ng/mL) was estimated using noncompartmental analyses.
Time Frame
Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
Title
Time of Maximum Plasma Concentration (Tmax) of ABT-267 Following Monotherapy on Day 1
Description
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Time of maximum plasma concentration (Tmax; measured in hours) was estimated using noncompartmental analyses.
Time Frame
Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
Title
Area Under the Plasma Concentration-time Curve From Time 0 to 24 Hours (AUC[24]) of ABT-267 Following Monotherapy on Day 1
Description
Blood samples were collected pre-dose (time 0) and at 2, 4, and 6 hours post-dose on Day 1 and pre-dose on Day 2 (ABT-267 monotherapy). The samples were analyzed for ABT-267 using validated analytical methods. Area under the plasma concentration-time curve from time 0 to 24 hours (AUC[24]; measured in ng multiplied by hour/mL) was estimated using noncompartmental analyses.
Time Frame
Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)
Title
Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3
Description
Blood samples were collected pre-dose on Day 2 (prior to second dose of ABT-267 monotherapy) and pre-dose on Day 3 (prior to first dose of combination therapy). The samples were analyzed for ABT-267 using validated analytical methods. Pre-dose plasma concentrations on Day 2 and Day 3 (Ctrough, measured in ng/mL) are reported.
Time Frame
Day 2 (pre-dose) and Day 3 (pre-dose)
Title
Number of Participants With Adverse Events (AEs)
Description
An adverse event was defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product and that did not necessarily have a causal relationship with this treatment.
The investigator assessed the relationship of each AE to the use of direct-acting antiviral agents (DAAs), and rated the severity of each event as either: Mild: The AE was transient and easily tolerated by the participant; Moderate: The AE caused the participant discomfort and interrupted usual activities; Severe: The AE caused considerable interference with the participant's usual activities and could have been incapacitating or life-threatening.
A serious adverse event was any event that resulted in death, was life-threatening, resulted in hospitalization or prolongation of hospitalization, resulted in a congenital anomaly or persistent or significant disability or was any other important medical event requiring medical or surgical intervention.
Time Frame
All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks).
Title
Mean Maximal Decrease From Baseline in Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) During ABT-267 Monotherapy
Description
The baseline value was the last measurement before the first dose of ABT-267 monotherapy (Day 1). The maximal decrease during monotherapy was the change from baseline to the lowest log10 IU/mL HCV RNA level any time from the first dose of ABT-267 on Day 1 to the last log10 HCV RNA level before the first dose of ABT-267 combination therapy (Study Day 3).
Time Frame
Pre-dose on Days 1, 2, and 3
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Virologic Response 12 Weeks and 24 Weeks After Combination Therapy
Description
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 and 24 weeks after the last dose of combination study drug. The LLOQ for the assay was 25 IU/mL.
Time Frame
12 and 24 weeks after last dose of combination study drug
Title
Percentage of Participants With Rapid Virologic Response
Description
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) after 4 weeks of combination therapy.
Time Frame
4 weeks
Title
Percentage of Participants With End-of-Treatment Response
Description
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) at the end of combination therapy (12 weeks).
Time Frame
12 weeks
Title
Percentage of Participants With Extended Rapid Virologic Response
Description
The percentage of participants with virologic response (plasma HCV RNA less than the lower limit of quantitation [< LLOQ]) at Weeks 4 through 12 of combination therapy.
Time Frame
Weeks 4 to 12
Title
Mean Change in Viral Load From Baseline to Pre-dose on Day 2 and Day 3 of ABT-267 Monotherapy
Description
The relationship between ABT-267 dose, ABT-267 concentration, and response was analyzed as the change in viral load (measured as log10 IU/mL) from baseline (pre-dose on Day 1) to pre-dose on Days 2 and 3. Plasma concentrations of ABT-267 pre-dose on Days 2 and 3 are presented above in 4. Primary Outcome: Plasma Concentration of ABT-267 Pre-dose (Ctrough) on Day 2 and Day 3.
Time Frame
Predose on Days 1, 2, and 3
Other Pre-specified Outcome Measures:
Title
Resistance-Associated Variants and Phenotypic Resistance
Description
Baseline (pre-dose on Day 1) samples were analyzed for resistance-associated amino acid (AA) variants using population sequencing. Phenotypic resistance to ABT-267 at Baseline was assessed by calculating the fold difference in the the half maximal effective concentration (EC50) compared with the EC50 for the appropriate reference replicon (1a-H77 or 1b-Con1). Day 3 samples were analyzed using population sequencing and were compared with the baseline and appropriate prototypic reference sequences to assess AA changes. Phenotypic resistance at Day 3 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 AA positions and phenotypic resistance at Baseline and Day 3 are presented.
Time Frame
Day 1 Pre-dose (Baseline) and Day 3 Pre-dose
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female between the age of 18 and 70 years, inclusive, at time of enrollment.
Subject has never received antiviral treatment for hepatitis C virus (HCV) infection.
Body mass index (BMI) is ≥ 18 to < 38 kg/m^2. BMI is calculated as weight measured in kilograms (kg) divided by the square of height measured in meters (m).
Chronic HCV genotype 1-infection for at least 6 months prior to study enrollment.
Subject has plasma HCV RNA level > 10,000 IU/mL at screening
Exclusion Criteria:
History of severe, life-threatening or other significant sensitivity to any drug.
Females who are or plan to become pregnant or breastfeeding or males whose partner is pregnant or planning to become pregnant.
Recent history of drug or alcohol abuse that could preclude adherence to the protocol.
Positive test result for hepatitis B surface antigen or anti-human immunodeficiency virus (HIV) antibodies.
Any current or past clinical evidence of cirrhosis (e.g., ascites, esophageal varices), or a liver biopsy or FibroTest/aspartate aminotransferase to platelet ratio (APRI) or FibroScan® showing cirrhosis or extensive bridging fibrosis.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew L Campbell, MD
Organizational Affiliation
AbbVie
Official's Role
Study Director
Facility Information:
Facility Name
Site Reference ID/Investigator# 68002
City
Bakersfield
State/Province
California
ZIP/Postal Code
93301
Country
United States
Facility Name
Site Reference ID/Investigator# 67383
City
Orlando
State/Province
Florida
ZIP/Postal Code
32809
Country
United States
Facility Name
Site Reference ID/Investigator# 67382
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21401
Country
United States
Facility Name
Site Reference ID/Investigator# 67385
City
Poughkeepsie
State/Province
New York
ZIP/Postal Code
12601
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
26597291
Citation
Mensing S, Polepally AR, Konig D, Khatri A, Liu W, Podsadecki TJ, Awni WM, Menon RM, Dutta S. Population Pharmacokinetics of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin in Patients with Hepatitis C Virus Genotype 1 Infection: Combined Analysis from 9 Phase 1b/2 Studies. AAPS J. 2016 Jan;18(1):270-80. doi: 10.1208/s12248-015-9846-1. Epub 2015 Nov 23.
Results Reference
background
Links:
URL
http://rxabbvie.com
Description
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Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
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