Study to Assess the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of ABT-267 in HCV Infected Subjects
Study Details
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: ABT-267 1.5 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV 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 |
Drug: ABT-267
Tablet
Other Names:
Drug: ABT-450
Tablet
Drug: ABT-333
Tablet
Other Names:
Drug: Ritonavir
Capsule
Drug: Ribavirin
Tablet
|
| Experimental: ABT-267 25 mg, then ABT-267, ABT-450/r, ABT-333, plus RBV 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 |
Drug: ABT-267
Tablet
Other Names:
Drug: ABT-450
Tablet
Drug: ABT-333
Tablet
Other Names:
Drug: Ritonavir
Capsule
Drug: Ribavirin
Tablet
|
Outcome Measures
Primary Outcome Measures
- Maximum Plasma Concentration (Cmax) of ABT-267 Following Monotherapy on Day 1 [Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)]
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 [Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)]
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 [Day 1 (pre-dose [time 0] and at 2, 4, and 6 hours post-dose) and Day 2 (pre-dose)]
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 [Day 2 (pre-dose) and Day 3 (pre-dose)]
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) [All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks).]
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 [Pre-dose on Days 1, 2, and 3]
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 [12 and 24 weeks after last dose of combination 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 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 [4 weeks]
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 [12 weeks]
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 [Weeks 4 to 12]
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 [Predose on Days 1, 2, and 3]
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.
Other Outcome Measures
- Resistance-Associated Variants and Phenotypic Resistance [Day 1 Pre-dose (Baseline) and Day 3 Pre-dose]
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.
Eligibility Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Site Reference ID/Investigator# 68002 | Bakersfield | California | United States | 93301 |
| 2 | Site Reference ID/Investigator# 67383 | Orlando | Florida | United States | 32809 |
| 3 | Site Reference ID/Investigator# 67382 | Annapolis | Maryland | United States | 21401 |
| 4 | Site Reference ID/Investigator# 67385 | Poughkeepsie | New York | United States | 12601 |
Sponsors and Collaborators
- AbbVie (prior sponsor, Abbott)
Investigators
- Study Director: Andrew L Campbell, MD, AbbVie
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- M13-386
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | 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/Group 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 |
| Period Title: Overall Study | ||
| STARTED | 6 | 6 |
| COMPLETED | 5 | 4 |
| NOT COMPLETED | 1 | 2 |
Baseline Characteristics
| Arm/Group Title | 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 | Total |
|---|---|---|---|
| Arm/Group 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 | Total of all reporting groups |
| Overall Participants | 6 | 6 | 12 |
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
51.5
(4.76)
|
46.8
(11.84)
|
49.2
(8.94)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
4
66.7%
|
3
50%
|
7
58.3%
|
| Male |
2
33.3%
|
3
50%
|
5
41.7%
|
Outcome Measures
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (intent-to-treat [ITT] population). |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Mean (Standard Deviation) [ng/mL] |
1.66
(0.21)
|
41.0
(16.5)
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population). |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Mean (Standard Deviation) [hours] |
3.67
(0.82)
|
3.67
(1.5)
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population). |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Mean (Standard Deviation) [ng*hr/mL] |
18.0
(2.46)
|
467
(236)
|
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population). |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Day 2 Ctrough |
0
(0)
|
5.2
(1.78)
|
| Day 3 Ctrough |
0.228
(0.263)
|
6.62
(3.77)
|
| 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). |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (safety population). |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Any AE |
3
50%
|
5
83.3%
|
| Any AE at least possibly related to DAAs |
3
50%
|
4
66.7%
|
| Any severe AE |
0
0%
|
1
16.7%
|
| Any serious AE |
0
0%
|
2
33.3%
|
| Any AE leading to discontinuation of study drug |
0
0%
|
1
16.7%
|
| Any AE leading to interruption of study drug |
0
0%
|
0
0%
|
| Any AE leading to RBV dose modification |
0
0%
|
1
16.7%
|
| Any fatal AE |
0
0%
|
0
0%
|
| Deaths |
0
0%
|
0
0%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders. |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| 12 Weeks Post-treatment |
83.3
1388.3%
|
83.3
1388.3%
|
| 24 Weeks Post-treatment |
83.3
1388.3%
|
83.3
1388.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders. |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Number [percentage of participants] |
83.3
1388.3%
|
100
1666.7%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders. |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Number [percentage of participants] |
83.3
1388.3%
|
83.3
1388.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population); participants with missing data were counted as non-responders. |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Number [percentage of participants] |
83.3
1388.3%
|
83.3
1388.3%
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population). |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Day 2 Mean change in Viral Load from Baseline |
-1.95
(0.630)
|
-2.85
(0.421)
|
| Day 3 Mean change in Viral Load from Baseline |
-1.96
(0.405)
|
-3.10
(0.257)
|
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population). |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Least Squares Mean (Standard Error) [log10 IU/mL] |
-1.6
(0.41)
|
-3.1
(0.41)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 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 |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.035 |
| Comments | Pre-specified 2-sided significance level of 0.05. | |
| Method | ANCOVA | |
| Comments | Analysis of covariance (ANCOVA) with the baseline log10 HCV RNA values as a covariate and with an effect for treatment arm. | |
| Method of Estimation | Estimation Parameter | Mean Difference (Maximal Decrease) |
| Estimated Value | -1.5 | |
| Confidence Interval |
(2-Sided) 95% -2.81 to -0.13 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of study drug (ITT population) and had evaluable data were analyzed for baseline resistance-associated amino acid variants; the development of viral resistance was analyzed in all participants who received at least 1 dose of ABT-267 whose samples had sufficient viral titer to allow analysis. |
| Arm/Group Title | 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/Group 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 |
| Measure Participants | 6 | 6 |
| Baseline Variants in NS5A (n=5, 6) |
2
33.3%
|
0
0%
|
| Baseline Resistance >10-fold (n=5, 6) |
1
16.7%
|
0
0%
|
| Day 3 Variants in NS5A (n=5, 2) |
6
100%
|
2
33.3%
|
| Day 3 Resistance >10-fold (n=5, 2) |
1
16.7%
|
2
33.3%
|
Adverse Events
| Time Frame | All AEs were collected from the time of study drug administration to 30 days after last dose of study drug (16 weeks); SAEs were also collected from the time that informed consent was obtained until the end of the study (60 weeks). | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | 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/Group 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 | ||
All Cause Mortality |
||||
| 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 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| 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 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/6 (0%) | 2/6 (33.3%) | ||
| Infections and infestations | ||||
| LABYRINTHITIS | 0/6 (0%) | 1/6 (16.7%) | ||
| Psychiatric disorders | ||||
| MANIA | 0/6 (0%) | 1/6 (16.7%) | ||
Other (Not Including Serious) Adverse Events |
||||
| 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 | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/6 (50%) | 5/6 (83.3%) | ||
| Cardiac disorders | ||||
| TACHYCARDIA | 0/6 (0%) | 1/6 (16.7%) | ||
| Gastrointestinal disorders | ||||
| DIARRHOEA | 1/6 (16.7%) | 2/6 (33.3%) | ||
| DRY MOUTH | 0/6 (0%) | 1/6 (16.7%) | ||
| NAUSEA | 0/6 (0%) | 1/6 (16.7%) | ||
| General disorders | ||||
| ASTHENIA | 0/6 (0%) | 1/6 (16.7%) | ||
| CHEST PAIN | 0/6 (0%) | 1/6 (16.7%) | ||
| FATIGUE | 1/6 (16.7%) | 2/6 (33.3%) | ||
| Infections and infestations | ||||
| GASTROENTERITIS | 0/6 (0%) | 1/6 (16.7%) | ||
| UPPER RESPIRATORY TRACT INFECTION | 1/6 (16.7%) | 0/6 (0%) | ||
| Injury, poisoning and procedural complications | ||||
| EXCORIATION | 0/6 (0%) | 1/6 (16.7%) | ||
| Investigations | ||||
| BLOOD BILIRUBIN INCREASED | 0/6 (0%) | 2/6 (33.3%) | ||
| HAEMOGLOBIN DECREASED | 0/6 (0%) | 2/6 (33.3%) | ||
| Metabolism and nutrition disorders | ||||
| DEHYDRATION | 0/6 (0%) | 1/6 (16.7%) | ||
| HYPOKALAEMIA | 1/6 (16.7%) | 0/6 (0%) | ||
| VITAMIN D DEFICIENCY | 1/6 (16.7%) | 0/6 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| INTERVERTEBRAL DISC PROTRUSION | 1/6 (16.7%) | 0/6 (0%) | ||
| Nervous system disorders | ||||
| BURNING SENSATION | 0/6 (0%) | 1/6 (16.7%) | ||
| DIZZINESS | 0/6 (0%) | 1/6 (16.7%) | ||
| HEADACHE | 1/6 (16.7%) | 2/6 (33.3%) | ||
| RESTLESS LEGS SYNDROME | 1/6 (16.7%) | 0/6 (0%) | ||
| Psychiatric disorders | ||||
| ABNORMAL DREAMS | 1/6 (16.7%) | 1/6 (16.7%) | ||
| SLEEP DISORDER | 1/6 (16.7%) | 0/6 (0%) | ||
| Renal and urinary disorders | ||||
| DYSURIA | 0/6 (0%) | 1/6 (16.7%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| DYSPNOEA | 0/6 (0%) | 1/6 (16.7%) | ||
| SINUS CONGESTION | 0/6 (0%) | 1/6 (16.7%) | ||
| Skin and subcutaneous tissue disorders | ||||
| DERMATITIS | 0/6 (0%) | 1/6 (16.7%) | ||
| NIGHT SWEATS | 0/6 (0%) | 1/6 (16.7%) | ||
| RASH | 0/6 (0%) | 2/6 (33.3%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
AbbVie requests that any investigator or institution that plans on presenting/publishing results disclosure, provide written notification of their request 60 days prior to their presentation/publication. AbbVie requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if AbbVie needs to secure patent or proprietary protection.
Results Point of Contact
| Name/Title | Global Medical Services |
|---|---|
| Organization | AbbVie |
| Phone | 800-633-9110 |
- M13-386