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.
Brief Title
A Study Comparing Efficacy and Safety of ABT-493/ABT-530 to Sofosbuvir Dosed With Daclatasvir in Adults With HCV Genotype 3 Infection
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).
Categories
Completion Date
Completion Date Type
Actual
Conditions
Chronic Hepatitis C
Hepatitis C Virus
Genotype 3 Hepatitis C Virus
Eligibility 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.
* 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
interferon free
Hepatitis C
daclatasvir
Sovaldi
HCV
Hepatitis C Virus
Hepatitis C Genotype 3
Hep C
sofosbuvir
Chronic Hepatitis C
Daklinza
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT02640157
Org Class
Industry
Org Full Name
AbbVie
Org Study Id
M13-594
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome 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%.
Outcome Measure
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm A to Arm B
Outcome Time Frame
12 weeks after the last actual dose of study drug
Outcome 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%.
Outcome Measure
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Noninferiority of Arm C to Arm A
Outcome Time Frame
12 weeks after the last actual dose of study drug
Secondary Ids
Secondary Id
2015-002272-24
Secondary Outcomes
Outcome 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.
Outcome Time Frame
12 weeks after the last actual dose of study drug
Outcome Measure
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Superiority of Arm A to Arm B
Outcome 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.
Outcome 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
Outcome Measure
Percentage of Participants With On-treatment Virologic Failure
Outcome 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.
Outcome Time Frame
From the end of treatment through 12 weeks after the last dose of study drug
Outcome Measure
Percentage of Participants With Post-treatment Relapse
See Also Links
Url
Start Date
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Samuel Sigal
Investigator Email
ssigal@montefiore.org
Investigator Phone
718-920-6240
Categories Mesh Debug
Hepatitis --- HEPATITIS C, CHRONIC
Hepatitis --- HEPATITIS C
Blood Disorders --- BLOOD-BORNE INFECTIONS
HIV/AIDS --- BLOOD-BORNE INFECTIONS
Infectious Disease --- BLOOD-BORNE INFECTIONS
Hepatitis --- COMMUNICABLE DISEASES
HIV/AIDS --- COMMUNICABLE DISEASES
Infectious Disease --- COMMUNICABLE DISEASES
COVID-19 --- INFECTIONS
Infectious Disease --- INFECTIONS
Hepatitis --- HEPATITIS, VIRAL, HUMAN
COVID-19 --- VIRUS DISEASES
Hepatitis --- VIRUS DISEASES
Infectious Disease --- VIRUS DISEASES
COVID-19 --- RNA VIRUS INFECTIONS
Infectious Disease --- RNA VIRUS INFECTIONS
Hepatitis --- HEPATITIS, CHRONIC
Hepatitis --- HEPATITIS
Digestive System --- LIVER DISEASES
Liver --- LIVER DISEASES
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM DISEASES
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
MeSH Terms
HEPATITIS C, CHRONIC
HEPATITIS C
BLOOD-BORNE INFECTIONS
COMMUNICABLE DISEASES
INFECTIONS
HEPATITIS, VIRAL, HUMAN
VIRUS DISEASES
FLAVIVIRIDAE INFECTIONS
RNA VIRUS INFECTIONS
HEPATITIS, CHRONIC
HEPATITIS
LIVER DISEASES
DIGESTIVE SYSTEM DISEASES
CHRONIC DISEASE
DISEASE ATTRIBUTES
PATHOLOGIC PROCESSES
PATHOLOGICAL CONDITIONS, SIGNS AND SYMPTOMS
GLECAPREVIR
PIBRENTASVIR
GLECAPREVIR AND PIBRENTASVIR
SOFOSBUVIR
DACLATASVIR
URIDINE MONOPHOSPHATE
URACIL NUCLEOTIDES
PYRIMIDINE NUCLEOTIDES
PYRIMIDINES
HETEROCYCLIC COMPOUNDS, 1-RING
HETEROCYCLIC COMPOUNDS
NUCLEOTIDES
NUCLEIC ACIDS, NUCLEOTIDES, AND NUCLEOSIDES
RIBONUCLEOTIDES