Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.

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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02640157
Recruitment Status : Completed
First Posted : December 28, 2015
Results First Posted : September 15, 2017
Last Update Posted : September 15, 2017
Sponsor:
Information provided by (Responsible Party):
AbbVie

Brief Summary:
The purpose of this study was to compare the safety and efficacy of ABT-493/ABT-530 to the combination of sofosbuvir (SOF) and daclatasvir (DCV) in adults with genotype 3 (GT3) chronic hepatitis C virus (HCV) infection.

Condition or disease Intervention/treatment Phase
Chronic Hepatitis C Hepatitis C Virus Genotype 3 Hepatitis C Virus Drug: ABT-493/ABT-530 Drug: Sofosbuvir Drug: Daclatasvir Phase 3

Detailed Description:
This study was a Phase 3, randomized, open-label, active-controlled multicenter study to compare efficacy and safety of ABT-493/ABT-530 to SOF and DCV in treatment-naïve chronic HCV GT3-infected participants without cirrhosis. The study consisted of 2 periods, a treatment period (participants received 8 or 12 weeks of ABT-493/ABT-530 or 12 weeks of SOF with DCV) and a post-treatment period (participants who completed or prematurely discontinued the treatment period were followed for 24 weeks after their last dose of study drug to evaluate efficacy and to monitor HCV RNA and the emergence and persistence of viral variants).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 506 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Active-Controlled, Multicenter Study to Compare Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Co-Administered With Daclatasvir in Adults With Chronic Hepatitis C Virus Genotype 3 Infection (ENDURANCE-3)
Study Start Date : December 2015
Actual Primary Completion Date : October 2016
Actual Study Completion Date : February 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm A
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 12 weeks.
Drug: ABT-493/ABT-530
Tablet; ABT-493 coformulated with ABT-530
Other Names:
  • ABT-493 also known as glecaprevir
  • ABT-530 also known as pibrentasvir
  • MAVYRET

Active Comparator: Arm B
Sofosbuvir 400 mg once daily (QD) co-administered with daclatasvir 60 mg QD for 12 weeks.
Drug: Sofosbuvir
Tablet
Other Name: Sovaldi

Drug: Daclatasvir
Tablet
Other Name: Daklinza

Experimental: Arm C
ABT-493/ABT-530 (300 mg/120 mg) coformulated once daily (QD) for 8 weeks.
Drug: ABT-493/ABT-530
Tablet; ABT-493 coformulated with ABT-530
Other Names:
  • ABT-493 also known as glecaprevir
  • ABT-530 also known as pibrentasvir
  • MAVYRET




Primary Outcome Measures :
  1. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm A to Arm B [ Time Frame: 12 weeks after the last actual dose of study drug ]
    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%.

  2. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm C to Arm A [ Time Frame: 12 weeks after the last actual dose of study drug ]
    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%.


Secondary Outcome Measures :
  1. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Superiority of Arm A to Arm B [ Time Frame: 12 weeks after the last actual dose of study drug ]
    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.

  2. Percentage of Participants With On-treatment Virologic Failure [ 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 ]
    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.

  3. Percentage of Participants With Post-treatment Relapse [ Time Frame: From the end of treatment through 12 weeks after the last dose of study drug ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female (of nonchildbearing potential, practicing total abstinence, sexually active with female partners only, or using allowed contraceptive methods) at least 18 years of age at time of screening.
  • Screening laboratory result indicating HCV GT3 infection.
  • Chronic HCV infection, defined as one of the following:

    • Positive for anti-HCV antibody (Ab) or HCV RNA at least 6 months before screening; or
    • A liver biopsy consistent with chronic HCV infection; or
    • Abnormal alanine aminotransferase (ALT) levels for at least 6 months before screening.
  • Hepatitis C virus treatment-naïve (i.e., participant had never received any anti-HCV treatment).
  • Documented as noncirrhotic.

Exclusion Criteria:

  • Female who was pregnant, planning to become pregnant during the study, or breastfeeding; or male whose partner was pregnant or planning to become pregnant during the study.
  • Recent (within 6 months prior to study drug administration) history of drug or alcohol abuse that could have precluded adherence to the protocol in the opinion of the investigator.
  • Positive test result at screening for hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus Ab (HIV Ab).
  • Hepatitis C virus genotyping performed during screening indicated co-infection with more than one HCV genotype.
  • Any cause of liver disease other than chronic HCV infection.
  • Consideration by the investigator, for any reason, that the participant was an unsuitable candidate to receive ABT-493/ABT-530, SOF, or DCV.
  • History of severe, life-threatening, or other significant sensitivity to any excipients of the study drug.
  • Previous use of any anti-HCV treatment.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02640157


Sponsors and Collaborators
AbbVie
Investigators
Layout table for investigator information
Study Director: AbbVie Inc AbbVie

Additional Information:
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 Posted: December 28, 2015    Key Record Dates
Results First Posted: September 15, 2017
Last Update Posted: September 15, 2017
Last Verified: August 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AbbVie:
interferon free
Hepatitis C
daclatasvir
Sovaldi
HCV
Hepatitis C Virus
Hepatitis C Genotype 3
Hep C
sofosbuvir
Chronic Hepatitis C
Daklinza
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Hepatitis, Chronic
Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Sofosbuvir
Antiviral Agents
Anti-Infective Agents