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A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Subjects With Genotype 1 Infection

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ClinicalTrials.gov Identifier: NCT02604017
Recruitment Status : Completed
First Posted : November 13, 2015
Results First Posted : September 14, 2017
Last Update Posted : September 14, 2017
Sponsor:
Information provided by (Responsible Party):
AbbVie

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Chronic Hepatitis C
Hepatitis C Virus
HCV
Intervention Drug: ABT-493/ABT-530
Enrollment 703
Recruitment Details  
Pre-assignment Details This study included a 35-day screening period.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Period Title: Overall Study
Started [1] 352 351
Completed 346 343
Not Completed 6 8
Reason Not Completed
Withdrew Consent             0             2
Lost to Follow-up             5             6
Not Specified             1             0
[1]
Intent-to-treat population: all participants who received at least 1 dose of study drug.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks Total
Hide Arm/Group Description ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks. Total of all reporting groups
Overall Number of Baseline Participants 352 351 703
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of study drug (ITT population).
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 352 participants 351 participants 703 participants
50.27  (11.62) 51.58  (11.90) 50.93  (11.77)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 352 participants 351 participants 703 participants
Female 176 184 360
Male 176 167 343
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Mono-infected Hepatitis C Virus Genotype 1 (HCV GT1), Direct-acting Antiviral Agent (DAA) Naïve Participants in the 12-Week Treatment Arm
Hide Description SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification [<LLOQ]) 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 in the 12-week treatment group compared with the historical control rate for HCV GT1 subjects who are treatment-naïve or treated with pegylated-interferon alfa-2a or alfa-2b and ribavirin (pegIFN/RBV).
Time Frame 12 weeks after the last actual dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population who were mono-infected HCV GT1, DAA-naïve; participants with missing data after backwards imputation were imputed as nonresponders.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Overall Number of Participants Analyzed 332
Measure Type: Number
Unit of Measure: percentage of participants
99.7
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABT-493/ABT-530 for 12 Weeks
Comments Based on a 2-sided significance level of 0.05 and an underlying rate of ≥97% in the 12-week arm, 270 participants provides >90% power to demonstrate noninferiority of the 12-week arm to the historical control rate for HCV GT1 subjects who are treatment-naïve or treated with pegIFN/RBV (based on the normal approximation of a single binomial proportion in a one-sample test for superiority).
Type of Statistical Test Non-Inferiority
Comments The noninferiority of the rate of SVR12 for the 12-week treatment group as compared with the historical rate was analyzed; the lower confidence bound of the 2-sided 95% confidence interval (95% CI) for the percentage of participants with SVR12 must exceed 91% to achieve noninferiority.
Method of Estimation Estimation Parameter Percentage of Participants
Estimated Value 99.7
Confidence Interval (2-Sided) 95%
99.1 to 100.0
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With SVR12: Noninferiority of 8-Week Arm to 12-Week Arm in Mono-infected HCV GT1, DAA-Naïve Participants, Excluding Those Who Discontinued/Experienced Virologic Failure by Week 8 or Had No HCV RNA Value at Week 12 or Later
Hide Description SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants (excluding those who discontinued/experienced virologic failure by Week 8 or had no HCV RNA value at Week 12 or later) who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm.
Time Frame 12 weeks after last actual dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population who were mono-infected HCV GT1 DAA-naïve (excluding those who discontinued/experienced virologic failure by Week 8 or had no HCV RNA value at Week 12 or later); participants with missing data after backwards imputation were imputed as nonresponders.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 331 332
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100.0
(98.9 to 100.0)
100
(98.9 to 100.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABT-493/ABT-530 for 12 Weeks, ABT-493/ABT-530 for 8 Weeks
Comments Based on a 2-sided significance level of 0.05 and an -5% noninferiority margin and an underlying rate of ≥97% in the 8-week arm (270 participants) and ≥97% in the 12-week arm (270 participants) provides >90% power to demonstrate noninferiority of the 8-week arm to the 12-week arm.
Type of Statistical Test Non-Inferiority
Comments The noninferiority of the rate of SVR12 for the 8-week treatment group as compared with the 12-week treatment group was analyzed; the lower confidence bound of the 2-sided 95% confidence interval (95% CI) for the difference in percentage of participants with SVR12 (8-week group minus 12-week group) must be above -5% to achieve noninferiority.
Method of Estimation Estimation Parameter Difference in Percentage of Participants
Estimated Value 0.0
Confidence Interval (2-Sided) 95%
-1.1 to 1.1
Estimation Comments [Not Specified]
3.Primary Outcome
Title Percentage of Participants With SVR12: Noninferiority of 8-Week Treatment Arm to 12-Week Treatment Arm in Mono-infected HCV GT1, DAA-Naïve Participants
Hide Description SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. The primary efficacy endpoint was noninferiority of the percentage of mono-infected HCV GT1, DAA-naïve participants who achieved SVR12 in the 8-week treatment arm compared with the 12-week treatment arm.
Time Frame 12 weeks after the last actual dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population who were mono-infected HCV GT1, DAA-naïve; participants with missing data after backwards imputation were imputed as nonresponders.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 332 335
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
99.7
(99.1 to 100.0)
99.1
(98.1 to 100.0)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection ABT-493/ABT-530 for 12 Weeks, ABT-493/ABT-530 for 8 Weeks
Comments Based on a 2-sided significance level of 0.05 and a -5% noninferiority margin, and an underlying rate of ≥97% in the 8-week arm (270 participants) and ≥97% in the 12-week arm (270 participants) provides >90% power to demonstrate noninferiority of the 8-week arm to the 12-week arm.
Type of Statistical Test Non-Inferiority
Comments The noninferiority of the rate of SVR12 for the 8-week treatment group as compared with the 12-week treatment group was analyzed; the lower confidence bound of the 2-sided 95% confidence interval (95% CI) for the difference in percentage of participants with SVR12 must be above -5% to achieve noninferiority.
Method of Estimation Estimation Parameter Difference in Percentage of Participants
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.8 to 0.6
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percentage of Participants With SVR12 in Mono-infected HCV GT1 Participants
Hide Description SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug.
Time Frame 12 weeks after last actual dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population who were mono-infected HCV GT1; participants with missing data after backwards imputation were imputed as nonresponders.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 334 336
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
99.7
(98.3 to 99.9)
99.1
(97.4 to 99.7)
5.Secondary Outcome
Title Percentage of Participants With SVR12
Hide Description SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug.
Time Frame 12 weeks after last actual dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population; participants with missing data after backwards imputation were imputed as nonresponders.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 352 351
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
99.7
(98.4 to 99.9)
99.1
(97.5 to 99.7)
6.Secondary Outcome
Title Percentage of Participants With SVR12 in Co-infected HCV GT1/Human Immunodeficiency Virus Type 1 (HIV-1) Participants
Hide Description SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug.
Time Frame 12 weeks after last actual dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population who were co-infected HCV GT1/HIV-1; participants with missing data after backwards imputation were imputed as nonresponders.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 18 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100.0
(82.4 to 100.0)
100.0
(79.6 to 100.0)
7.Secondary Outcome
Title Percentage of Participants With SVR12 in HCV GT1-infected, Prior Sofosbuvir (SOF) Treatment-Experienced Participants
Hide Description SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug.
Time Frame 12 weeks after last actual dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population who were HCV GT1-infected, prior SOF-treatment experienced; participants with missing data after backwards imputation were imputed as nonresponders.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 2 1
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100.0
(34.2 to 100.0)
100.0
(20.7 to 100.0)
8.Secondary Outcome
Title Percentage of Participants With On-treatment Virologic Failure
Hide Description On-treatment virologic failure was defined as confirmed increase of >1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment; confirmed HCV RNA ≥100 IU/mL after HCV RNA <LLOQ during treatment, or HCV RNA ≥LLOQ at end of treatment with at least 6 weeks of treatment.
Time Frame Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug (ITT population).
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 352 351
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of particpants
0.0
(0.0 to 1.1)
0.3
(0.1 to 1.6)
9.Secondary Outcome
Title Percentage of Participants With On-treatment Virologic Failure in Mono-infected HCV GT1, DAA-Naïve Participants
Hide Description On-treatment virologic failure was defined as confirmed increase of >1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline HCV RNA during treatment; confirmed HCV RNA ≥100 IU/mL after HCV RNA <LLOQ during treatment, or HCV RNA ≥LLOQ at end of treatment with at least 6 weeks of treatment.
Time Frame Treatment Weeks 1, 2, 4, 8 (end of treatment for 8-week treatment arm), and 12 (end of treatment for 12-week treatment arm) or premature discontinuation from treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population who were mono-infected HCV GT1, DAA-naïve.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 332 335
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 1.1)
0.3
(0.1 to 1.7)
10.Secondary Outcome
Title Percentage of Participants With Post-treatment Relapse
Hide Description Post-treatment relapse was defined as confirmed HCV RNA ≥LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels <LLOQ at the end of treatment, excluding reinfection.
Time Frame From the end of treatment through 12 weeks after the last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug, completed treatment, and had HCV RNA <LLOQ at the final treatment visit.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 352 349
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 1.1)
0.0
(0.0 to 1.1)
11.Secondary Outcome
Title Percentage of Participants With Post-treatment Relapse in Mono-infected HCV GT1, DAA-Naïve Participants
Hide Description Post-treatment relapse was defined as confirmed HCV RNA ≥LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels <LLOQ at the end of treatment, excluding reinfection.
Time Frame From the end of treatment through 12 weeks after the last dose of study drug
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT population who were mono-infected HCV GT1, DAA-naïve, received at least 1 dose of study drug, completed treatment, and had HCV RNA <LLOQ at the final treatment visit.
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 332 333
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.0
(0.0 to 1.1)
0.0
(0.0 to 1.1)
Time Frame Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 16 weeks).
Adverse Event Reporting Description TEAEs and TESAEs are defined as any AE or SAE with an onset or worsening date that is after the first dose of study drug until 30 days after the last dose of study drug and were collected whether elicited or spontaneously reported by the participant.
 
Arm/Group Title ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Hide Arm/Group Description ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
All-Cause Mortality
ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Affected / at Risk (%) Affected / at Risk (%)
Total   4/352 (1.14%)   5/351 (1.42%) 
Cardiac disorders     
ANGINA UNSTABLE  1  0/352 (0.00%)  1/351 (0.28%) 
ATRIAL FIBRILLATION  1  1/352 (0.28%)  0/351 (0.00%) 
Gastrointestinal disorders     
IRRITABLE BOWEL SYNDROME  1  1/352 (0.28%)  0/351 (0.00%) 
Infections and infestations     
BRONCHITIS  1  1/352 (0.28%)  0/351 (0.00%) 
Injury, poisoning and procedural complications     
ALCOHOL POISONING  1  1/352 (0.28%)  0/351 (0.00%) 
ARTERIAL INJURY  1  0/352 (0.00%)  1/351 (0.28%) 
RADIUS FRACTURE  1  0/352 (0.00%)  1/351 (0.28%) 
TOXICITY TO VARIOUS AGENTS  1  1/352 (0.28%)  0/351 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
UTERINE LEIOMYOMA  1  0/352 (0.00%)  1/351 (0.28%) 
Nervous system disorders     
TRANSIENT ISCHAEMIC ATTACK  1  0/352 (0.00%)  1/351 (0.28%) 
Psychiatric disorders     
SUICIDE ATTEMPT  1  0/352 (0.00%)  1/351 (0.28%) 
Respiratory, thoracic and mediastinal disorders     
PNEUMONIA ASPIRATION  1  1/352 (0.28%)  0/351 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ABT-493/ABT-530 for 12 Weeks ABT-493/ABT-530 for 8 Weeks
Affected / at Risk (%) Affected / at Risk (%)
Total   130/352 (36.93%)   133/351 (37.89%) 
Gastrointestinal disorders     
NAUSEA  1  29/352 (8.24%)  19/351 (5.41%) 
General disorders     
FATIGUE  1  43/352 (12.22%)  31/351 (8.83%) 
Infections and infestations     
NASOPHARYNGITIS  1  31/352 (8.81%)  22/351 (6.27%) 
Nervous system disorders     
HEADACHE  1  62/352 (17.61%)  68/351 (19.37%) 
Psychiatric disorders     
INSOMNIA  1  15/352 (4.26%)  21/351 (5.98%) 
Skin and subcutaneous tissue disorders     
PRURITUS  1  17/352 (4.83%)  20/351 (5.70%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (19.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02604017     History of Changes
Other Study ID Numbers: M13-590
2015-002087-17 ( EudraCT Number )
First Submitted: November 11, 2015
First Posted: November 13, 2015
Results First Submitted: August 17, 2017
Results First Posted: September 14, 2017
Last Update Posted: September 14, 2017