CERTAIN-2: A Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Genotype 2 Chronic Hepatitis C Virus Infection

Sponsor
AbbVie (Industry)
Overall Status
Completed
CT.gov ID
NCT02723084
Collaborator
(none)
136
Enrollment
2
Arms
11.5
Actual Duration (Months)

Study Details

Study Description

Brief Summary

The purpose of this phase 3 study is to evaluate the efficacy and safety of ABT-493/ABT-530 in comparison to sofosbuvir plus ribavirin for 12 weeks in Hepatitis C Virus (HCV) Genotype 2 (GT2) infected participants.

Condition or DiseaseIntervention/TreatmentPhase
Phase 3

Detailed Description

This was a randomized, open-label, active-control, multicenter study to evaluate efficacy, safety, and pharmacokinetics of ABT-493/ABT-530 in chronic HCV GT2-infected direct-acting antiviral agent (DAA) treatment-naïve Japanese adult participants without cirrhosis. The participants were randomized in a 2:1 ratio to ABT-493/ABT-530 for 8 weeks (Arm A) and sofosbuvir plus ribavirin for 12 weeks (Arm B).

Study Design

Study Type:
Interventional
Actual Enrollment :
136 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-Label, Active Comparator, Multicenter Study to Evaluate the Efficacy and Safety of ABT-493/ABT-530 in Japanese Adults With Genotype 2 Chronic Hepatitis C Virus Infection (CERTAIN-2)
Actual Study Start Date :
Apr 8, 2016
Actual Primary Completion Date :
Jan 19, 2017
Actual Study Completion Date :
Mar 24, 2017

Arms and Interventions

ArmIntervention/Treatment
Experimental: Arm A

Co-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis.

Drug: ABT-493/ABT-530
Co-formulated tablet
Other Names:
  • glecaprevir/pibrentasvir
  • glecaprevir (ABT-493)
  • pibrentasvir (ABT-530)
  • Active Comparator: Arm B

    sofosbuvir (400 mg) QD co-administered with weight based ribavirin (RBV) 600-1000 mg divided twice daily (BID) for 12 weeks in HCV GT2 -infected, DAA treatment-naïve participants without cirrhosis.

    Drug: sofosbuvir (SOF)
    Tablet

    Drug: ribavirin (RBV)
    Capsule

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Non-inferiority of Arm A to Arm B [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 non-inferiority of the ABT-493/ABT-530 8-week regimen (Arm A) to the sofosbuvir and ribavirin 12 week regimen (Arm B) in SVR12 using a non-inferiority margin of 10% in the intent-to-treat (ITT) population.

    Secondary Outcome Measures

    1. Percentage of Participants in Arm A With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) [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.

    2. Percentage of Participants With With On-treatment Virologic Failure [Treatment Weeks 1, 2, 4, 8 (end of treatment for arm A), and 12 (end of treatment for arm 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 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. 95% CI was calculated using the Wilson score method.

    3. Percentage of Participants With Post-Treatment Relapse [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 participants who were been shown to be re-infected. 95% CI was calculated using the Wilson score method.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Females were postmenopausal for at least 2 years prior to screening; surgically sterile or had a vasectomized partner; or, if of childbearing potential and sexually active with a male partner, were currently using at least 1 effective method of birth control at the time of Screening and agreed to practice 1 effective method of birth control from Screening through 30 days after stopping study drug. Sexually active males were surgically sterile or, if sexually active with a female partner of childbearing potential, agreed to practice 1 effective form of birth control from Screening through 30 days after stopping study drug.

    • Screening central laboratory result indicating HCV GT-2 infection without co-infection of any other genotype.

    • Participant has positive anti-HCV antibody (Ab) and plasma HCV RNA viral load greater than or equal to 1000 IU/mL at Screening Visit.

    • Chronic HCV infection defined as one of the following:

    • Positive for anti-HCV Ab and/or HCV RNA at least 6 months before Screening; or

    • A liver biopsy consistent with chronic HCV infection.

    • Participant must be HCV treatment-naïve (i.e., patient has not received a single dose of any approved or investigational DAA) and non-cirrhotic. Prior HCV treatment using IFNs with or without ribavirin is acceptable. Previous HCV Interferon (IFN) based treatment must have been completed greater than or equal to 2 months prior to screening.

    Exclusion Criteria:
    • Females who were pregnant or planned to become pregnant, or breastfeeding or males 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 preclude 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 antibody (HIV Ab).

    • Requirement for and inability to safely discontinue contraindicated medications or supplements at least 2 weeks or 10 half-lives (whichever is longer) prior to the first dose of any study drug.

    • Clinically significant abnormalities, other than HCV-infection, based upon the results of a medical history, physical examination, vital signs, laboratory profile, and a 12-lead electrocardiogram (ECG) that make the participant an unsuitable candidate for this study in the opinion of the investigator, including, but not limited to:

    • Uncontrolled diabetes as defined by a glycated hemoglobin (hemoglobin A1C) level

    8.5% at the Screening Visit.

    • Active or suspected malignancy or history of malignancy (other than basal cell skin cancer or cervical carcinoma in situ) in the past 5 years, or any history of hepatocellular carcinoma (HCC).

    • Uncontrolled cardiac, respiratory, gastrointestinal, hematologic, neurologic, psychiatric, or other medical disease or disorder, which is unrelated to the existing HCV infection.

    • Any cause of liver disease other than chronic HCV-infection, including but not limited to the following:

    • Hemochromatosis, alpha-1 antitrypsin deficiency, Wilson's disease, autoimmune hepatitis, alcoholic liver disease, or steatohepatitis considered to be the primary cause of the liver disease rather than concomitant/incidental with HCV infection.

    Contacts and Locations

    Locations

    No locations specified.

    Sponsors and Collaborators

    • AbbVie

    Investigators

    • Study Director: AbbVie Inc., MD, AbbVie

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT02723084
    Other Study ID Numbers:
    • M15-828
    First Posted:
    Mar 30, 2016
    Last Update Posted:
    Jul 16, 2021
    Last Verified:
    Jul 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by AbbVie
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailIntent-to-treat population: all participants who received at least 1 dose of study drug.
    Arm/Group TitleArm AArm B
    Arm/Group DescriptionCo-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis.sofosbuvir (400 mg) QD co-administered with weight based ribavirin (RBV) 600-1000 mg divided twice daily (BID) for 12 weeks in HCV GT2 -infected, DAA treatment-naïve participants without cirrhosis.
    Period Title: Overall Study
    STARTED9046
    COMPLETED8645
    NOT COMPLETED41

    Baseline Characteristics

    Arm/Group TitleArm AArm BTotal
    Arm/Group DescriptionCo-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis.sofosbuvir (400 mg) QD co-administered with weight based ribavirin (RBV) 600-1000 mg divided twice daily (BID) for 12 weeks in HCV GT2 -infected, DAA treatment-naïve participants without cirrhosis.Total of all reporting groups
    Overall Participants9046136
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    57.46
    (13.07)
    58.89
    (13.64)
    57.94
    (13.23)
    Sex: Female, Male (Count of Participants)
    Female
    48
    53.3%
    25
    54.3%
    73
    53.7%
    Male
    42
    46.7%
    21
    45.7%
    63
    46.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    90
    100%
    46
    100%
    136
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%

    Outcome Measures

    1. Primary Outcome
    TitlePercentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Non-inferiority of Arm A to Arm B
    DescriptionSVR12 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 non-inferiority of the ABT-493/ABT-530 8-week regimen (Arm A) to the sofosbuvir and ribavirin 12 week regimen (Arm B) in SVR12 using a non-inferiority margin of 10% in the intent-to-treat (ITT) population.
    Time Frame12 weeks after the last actual dose of study drug

    Outcome Measure Data

    Analysis Population Description
    Intent-to-treat (ITT) population: all participants who received at least 1 dose of study drug; participants with missing data after backwards imputation were imputed as nonresponders.
    Arm/Group TitleArm AArm B
    Arm/Group DescriptionCo-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis.sofosbuvir (400 mg) QD co-administered with weight based ribavirin (RBV) 600-1000 mg divided twice daily (BID) for 12 weeks in HCV GT2 -infected, DAA treatment-naïve participants without cirrhosis.
    Measure Participants9046
    Number [percentage of participants]
    97.8
    108.7%
    93.5
    203.3%
    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 The percentage of participants achieving SVR12 was calculated for each arm and a 2- sided 95% confidence interval (CI) for the difference in SVR12 rates (Arm A minus Arm B) was calculated using the normal approximation to the binomial distribution to assess non-inferiority in SVR12 rates of arm A to arm B. If the lower bound of the CI for the difference was above the noninferiority margin of -10%, then arm A was considered non-inferior to arm B.
    Statistical Test of Hypothesisp-Value
    Comments
    Method
    Comments
    Method of EstimationEstimation ParameterRisk Difference (RD)
    Estimated Value4.3
    Confidence Interval (2-Sided) 95%
    -3.5 to 12.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments95% CI was calculated using the normal approximation to the binomial distribution.
    2. Secondary Outcome
    TitlePercentage of Participants in Arm A With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
    DescriptionSVR12 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.
    Time Frame12 weeks after the last actual dose of study drug

    Outcome Measure Data

    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 TitleArm A
    Arm/Group DescriptionCo-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis.
    Measure Participants90
    Number (95% Confidence Interval) [percentage of participants]
    97.8
    108.7%
    3. Secondary Outcome
    TitlePercentage of Participants With With On-treatment Virologic Failure
    DescriptionOn-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. 95% CI was calculated using the Wilson score method.
    Time FrameTreatment Weeks 1, 2, 4, 8 (end of treatment for arm A), and 12 (end of treatment for arm B) or premature discontinuation from treatment

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug (ITT population).
    Arm/Group TitleArm AArm B
    Arm/Group DescriptionCo-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis.sofosbuvir (400 mg) QD co-administered with weight based ribavirin (RBV) 600-1000 mg divided twice daily (BID) for 12 weeks in HCV GT2 -infected, DAA treatment-naïve participants without cirrhosis.
    Measure Participants9046
    Number (95% Confidence Interval) [percentage of participants]
    0
    0%
    0
    0%
    4. Secondary Outcome
    TitlePercentage of Participants With Post-Treatment Relapse
    DescriptionPost-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 participants who were been shown to be re-infected. 95% CI was calculated using the Wilson score method.
    Time FrameFrom the end of treatment through 12 weeks after the last dose of study drug

    Outcome Measure Data

    Analysis Population Description
    All participants who received at least 1 dose of study drug (ITT population).
    Arm/Group TitleArm AArm B
    Arm/Group DescriptionCo-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis.sofosbuvir (400 mg) QD co-administered with weight based ribavirin (RBV) 600-1000 mg divided twice daily (BID) for 12 weeks in HCV GT2 -infected, DAA treatment-naïve participants without cirrhosis.
    Measure Participants8945
    Number (95% Confidence Interval) [percentage of participants]
    0
    0%
    4.4
    9.6%

    Adverse Events

    Time FrameTreatment-emergent adverse events (TEAEs) were collected from the time of study drug administration until 30 days after the last dose of study drug (up to 16 weeks). Serious adverse events (SAEs) were collected starting from the time that the informed consent was signed until the end of the study (up to 21 weeks).
    Adverse Event Reporting Description TEAEs and Treatment-emergent serious adverse events (TESAEs) are defined as any adverse event (AE) or serious adverse event (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 TitleARM AARM B
    Arm/Group DescriptionCo-formulated ABT-493/ABT-530 (300 mg/120 mg) administered once daily (QD) for 8 weeks in HCV genotype (GT) 2 -infected, DAA treatment-naïve participants without cirrhosis.sofosbuvir (400 mg) QD co-administered with weight based ribavirin (RBV) 600-1000 mg divided twice daily (BID) for 12 weeks in HCV GT2 -infected, DAA treatment-naïve participants without cirrhosis.
    All Cause Mortality
    ARM AARM B
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/90 (0%) 0/46 (0%)
    Serious Adverse Events
    ARM AARM B
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total2/90 (2.2%) 2/46 (4.3%)
    Cardiac disorders
    ANGINA UNSTABLE1/90 (1.1%) 0/46 (0%)
    Infections and infestations
    PNEUMONIA0/90 (0%) 1/46 (2.2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    CASTLEMAN'S DISEASE0/90 (0%) 1/46 (2.2%)
    Respiratory, thoracic and mediastinal disorders
    PNEUMOTHORAX SPONTANEOUS1/90 (1.1%) 0/46 (0%)
    Other (Not Including Serious) Adverse Events
    ARM AARM B
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total20/90 (22.2%) 26/46 (56.5%)
    Blood and lymphatic system disorders
    ANAEMIA0/90 (0%) 16/46 (34.8%)
    Gastrointestinal disorders
    NAUSEA3/90 (3.3%) 3/46 (6.5%)
    STOMATITIS1/90 (1.1%) 3/46 (6.5%)
    General disorders
    MALAISE5/90 (5.6%) 4/46 (8.7%)
    Infections and infestations
    NASOPHARYNGITIS9/90 (10%) 5/46 (10.9%)
    Investigations
    BLOOD BILIRUBIN INCREASED1/90 (1.1%) 7/46 (15.2%)
    Metabolism and nutrition disorders
    HYPERURICAEMIA0/90 (0%) 3/46 (6.5%)
    Nervous system disorders
    HEADACHE6/90 (6.7%) 1/46 (2.2%)

    Limitations/Caveats

    [Not Specified]

    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/TitleGlobal Medical Services
    OrganizationAbbVie
    Phone800-633-9110
    Emailabbvieclinicaltrials@abbvie.com
    Responsible Party:
    AbbVie
    ClinicalTrials.gov Identifier:
    NCT02723084
    Other Study ID Numbers:
    • M15-828
    First Posted:
    Mar 30, 2016
    Last Update Posted:
    Jul 16, 2021
    Last Verified:
    Jul 1, 2021