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A Study Comparing Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Dosed With Daclatasvir in Adults With HCV Genotype 3 Infection (ENDURANCE-3)

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ClinicalTrials.gov Identifier: NCT02640157
Recruitment Status : Completed
First Posted : December 28, 2015
Results First Posted : September 15, 2017
Last Update Posted : July 30, 2021
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
Genotype 3 Hepatitis C Virus
Interventions Drug: ABT-493/ABT-530
Drug: Sofosbuvir
Drug: Daclatasvir
Enrollment 506
Recruitment Details  
Pre-assignment Details A total of 506 participants were randomized and 505 received ≥ 1 dose of study drug. One participant in Arm B was randomized in error and never dispensed study drug. This participant is included in the total number of participants in Arm B who discontinued the study. This study included a 42-day screening period.
Arm/Group Title Arm A Arm B Arm C
Hide Arm/Group Description ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks. ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Period Title: Overall Study
Started 233 [1] 116 157 [1]
Received Study Drug 233 115 [2] 157
Completed Study Drug 225 112 154
Discontinued Study Drug 8 3 3
Completed 220 111 147
Not Completed 13 5 10
Reason Not Completed
Adverse Event             2             2             1
Withdrew consent             2             0             2
Lost to Follow-up             9             2             7
Randomized in error; did not receive Tx             0             1             0
[1]
Intent-to-treat population: all participants who received at least 1 dose of study drug
[2]
One participant in Arm B was randomized in error and never dispensed study drug.
Arm/Group Title Arm A Arm B Arm C Total
Hide Arm/Group Description ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg 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 233 115 157 505
Hide Baseline Analysis Population Description
All participants who received at least 1 dose of study drug (safety population)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 233 participants 115 participants 157 participants 505 participants
47.18  (10.68) 47.06  (11.31) 45.43  (12.19) 46.61  (11.32)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 233 participants 115 participants 157 participants 505 participants
Female 112 63 64 239
Male 121 52 93 266
1.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm A to Arm B
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 in the percentage of participants achieving SVR12 of the 12-week regimen (Arm A) to the standard of care (Arm B: 12 weeks of treatment with sofosbuvir [SOF] + daclatasvir [DCV]), defined as: a) the lower bound of the 95% confidence interval (CI) for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was greater than 92%; OR b) the lower bound of the 95% CI for the difference was below the non-inferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm A was greater than 92%; OR c) the lower bound of the 97.5% CI for the difference was above the non-inferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm A was below 92%.
Time Frame 12 weeks after the last actual dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: all participants who received at least 1 dose of study drug; participants with missing data after backwards imputation were counted as nonresponders.
Arm/Group Title Arm A Arm B
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.
Overall Number of Participants Analyzed 233 115
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.3
(92.6 to 98.0)
96.5
(93.2 to 99.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
Comments Difference in SVR12 rates (Arm A - Arm B).
Type of Statistical Test Non-Inferiority
Comments Noninferiority: a) the lower bound (LB) of the 95%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm A was >92%; or b) the LB of the 95%CI for the difference was below the non-inferiority margin of -6% and the LB of the 97.5%CI for the SVR12 rate within Arm A was >92%; or c) the LB of the 97.5%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm A was below 92%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value -1.2
Confidence Interval (2-Sided) 95%
-5.6 to 3.1
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm A
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Noninferiority: a) the lower bound (LB) of the 95%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm A was >92%; or b) the LB of the 95%CI for the difference was below the non-inferiority margin of -6% and the LB of the 97.5%CI for the SVR12 rate within Arm A was >92%; or c) the LB of the 97.5%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm A was below 92%.
Method of Estimation Estimation Parameter percentage of participants
Estimated Value 95.3
Confidence Interval (2-Sided) 97.5%
92.2 to 98.4
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Arm A, Arm B
Comments Difference in SVR12 rates (Arm A - Arm B).
Type of Statistical Test Non-Inferiority
Comments Noninferiority: a) the lower bound (LB) of the 95%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm A was >92%; or b) the LB of the 95%CI for the difference was below the non-inferiority margin of -6% and the LB of the 97.5%CI for the SVR12 rate within Arm A was >92%; or c) the LB of the 97.5%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm A was below 92%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value -1.2
Confidence Interval (2-Sided) 97.5%
-6.2 to 3.7
Estimation Comments [Not Specified]
2.Primary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm C to Arm A
Hide Description SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. If the first primary efficacy objective (noninferiority of Arm A to Arm B) was achieved, then the second primary efficacy objective, noninferiority in the percentage of participants achieving SVR12 of the 8-week regimen (Arm C) to the 12-week regimen (Arm A) was to be tested. Noninferiority was defined as: a) the lower bound of the 95% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was greater than 92%, OR b) the lower bound of the 95% CI for the difference was below the noninferiority margin of -6% and the lower bound of the 97.5% CI for the SVR12 rate within Arm C was greater than 92%, OR c) the lower bound of the 97.5% CI for the difference was above the noninferiority margin of -6% and the lower bound of the 95% CI for the SVR12 rate within Arm C was below 92%.
Time Frame 12 weeks after the last actual dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug (ITT population); participants with missing data after backwards imputation were imputed as nonresponders.
Arm/Group Title Arm A Arm C
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 233 157
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.3
(92.6 to 98.0)
94.9
(91.5 to 98.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
Comments Difference in SVR12 rates (Arm C - Arm A)
Type of Statistical Test Non-Inferiority
Comments Noninferiority: a) the lower bound (LB) of the 95%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm C was >92%; or b) the LB of the 95%CI for the difference was below the non-inferiority margin of -6% and the LB of the 97.5%CI for the SVR12 rate within Arm C was >92%; or c) the LB of the 97.5%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm C was below 92%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value -0.4
Confidence Interval (2-Sided) 95%
-4.8 to 4.0
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Arm C
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Noninferiority: a) the lower bound (LB) of the 95%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm C was >92%; or b) the LB of the 95%CI for the difference was below the non-inferiority margin of -6% and the LB of the 97.5%CI for the SVR12 rate within Arm C was >92%; or c) the LB of the 97.5%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm C was below 92%.
Method of Estimation Estimation Parameter Percentage of participants
Estimated Value 94.9
Confidence Interval (2-Sided) 97.5%
91.0 to 98.8
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Arm A, Arm C
Comments [Not Specified]
Type of Statistical Test Non-Inferiority
Comments Noninferiority: a) the lower bound (LB) of the 95%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm C was >92%; or b) the LB of the 95%CI for the difference was below the non-inferiority margin of -6% and the LB of the 97.5%CI for the SVR12 rate within Arm C was >92%; or c) the LB of the 97.5%CI for the difference was above the non-inferiority margin of -6% and the LB of the 95%CI for the SVR12 rate within Arm C was below 92%.
Method of Estimation Estimation Parameter Difference in percentage of participants
Estimated Value -0.4
Confidence Interval (2-Sided) 97.5%
-5.4 to 4.6
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Superiority of Arm A to Arm B
Hide Description SVR12 was defined as plasma HCV RNA level <LLOQ 12 weeks after the last dose of study drug. Per statistical analysis plan to adjust for multiplicity among the primary and first secondary hypothesis tests, the test for superiority of Arm A to Arm B was not conducted.
Time Frame 12 weeks after the last actual dose of study drug
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug (ITT population); participants with missing data after backwards imputation were imputed as nonresponders.
Arm/Group Title Arm A Arm B
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.
Overall Number of Participants Analyzed 233 115
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
95.3
(92.6 to 98.0)
96.5
(93.2 to 99.9)
4.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 in 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 Arm C), and 12 (end of treatment for Arms A and B) or premature discontinuation from treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of study drug (ITT population)
Arm/Group Title Arm A Arm B Arm C
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 233 115 157
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
0.4
(0.1 to 2.4)
0
(0.0 to 3.2)
0.6
(0.1 to 3.5)
5.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
Hide 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 Arm A Arm B Arm C
Hide Arm/Group Description:
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Overall Number of Participants Analyzed 222 114 150
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
1.4
(0.5 to 3.9)
0.9
(0.2 to 4.8)
3.3
(1.4 to 7.6)
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 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 Arm A ARM B ARM C
Hide Arm/Group Description ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks. ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
All-Cause Mortality
Arm A ARM B ARM C
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Arm A ARM B ARM C
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   5/233 (2.15%)   2/115 (1.74%)   3/157 (1.91%) 
Eye disorders       
ULCERATIVE KERATITIS  1  0/233 (0.00%)  0/115 (0.00%)  1/157 (0.64%) 
Infections and infestations       
OPHTHALMIC HERPES SIMPLEX  1  0/233 (0.00%)  0/115 (0.00%)  1/157 (0.64%) 
PNEUMONIA  1  1/233 (0.43%)  0/115 (0.00%)  0/157 (0.00%) 
Injury, poisoning and procedural complications       
ACCIDENTAL OVERDOSE  1  0/233 (0.00%)  0/115 (0.00%)  1/157 (0.64%) 
LIMB INJURY  1  1/233 (0.43%)  0/115 (0.00%)  0/157 (0.00%) 
POISONING  1  0/233 (0.00%)  0/115 (0.00%)  1/157 (0.64%) 
Metabolism and nutrition disorders       
IRON DEFICIENCY  1  0/233 (0.00%)  1/115 (0.87%)  0/157 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
PARANASAL SINUS AND NASAL CAVITY MALIGNANT NEOPLASM RECURRENT  1  1/233 (0.43%)  0/115 (0.00%)  0/157 (0.00%) 
Pregnancy, puerperium and perinatal conditions       
ABORTION MISSED  1  1/233 (0.43%)  0/115 (0.00%)  0/157 (0.00%) 
Psychiatric disorders       
DEPENDENCE  1  0/233 (0.00%)  0/115 (0.00%)  1/157 (0.64%) 
SUBSTANCE-INDUCED PSYCHOTIC DISORDER  1  0/233 (0.00%)  1/115 (0.87%)  0/157 (0.00%) 
Respiratory, thoracic and mediastinal disorders       
ACUTE RESPIRATORY FAILURE  1  1/233 (0.43%)  0/115 (0.00%)  0/157 (0.00%) 
HYPOXIA  1  1/233 (0.43%)  0/115 (0.00%)  0/157 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v.19.0
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Arm A ARM B ARM C
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   126/233 (54.08%)   53/115 (46.09%)   64/157 (40.76%) 
Gastrointestinal disorders       
DIARRHOEA  1  15/233 (6.44%)  4/115 (3.48%)  18/157 (11.46%) 
NAUSEA  1  32/233 (13.73%)  15/115 (13.04%)  19/157 (12.10%) 
VOMITING  1  10/233 (4.29%)  5/115 (4.35%)  9/157 (5.73%) 
General disorders       
ASTHENIA  1  4/233 (1.72%)  7/115 (6.09%)  3/157 (1.91%) 
FATIGUE  1  44/233 (18.88%)  16/115 (13.91%)  20/157 (12.74%) 
Infections and infestations       
NASOPHARYNGITIS  1  12/233 (5.15%)  6/115 (5.22%)  4/157 (2.55%) 
UPPER RESPIRATORY TRACT INFECTION  1  15/233 (6.44%)  4/115 (3.48%)  2/157 (1.27%) 
Nervous system disorders       
HEADACHE  1  60/233 (25.75%)  21/115 (18.26%)  31/157 (19.75%) 
Psychiatric disorders       
INSOMNIA  1  9/233 (3.86%)  6/115 (5.22%)  0/157 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA v.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
Layout table for Results Point of Contact information
Name/Title: Global Medical Services
Organization: AbbVie
Phone: 800-633-9110
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: AbbVie
ClinicalTrials.gov Identifier: NCT02640157    
Other Study ID Numbers: M13-594
2015-002272-24 ( EudraCT Number )
First Submitted: December 22, 2015
First Posted: December 28, 2015
Results First Submitted: August 17, 2017
Results First Posted: September 15, 2017
Last Update Posted: July 30, 2021