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
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 Disease | Intervention/Treatment | Phase |
---|---|---|
|
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
Arms and Interventions
Arm | Intervention/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:
|
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
- 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
- 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.
- 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.
- 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
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
- M15-828
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | Intent-to-treat population: all participants who received at least 1 dose of study drug. |
Arm/Group Title | Arm A | Arm B |
---|---|---|
Arm/Group Description | 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. | 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 | ||
STARTED | 90 | 46 |
COMPLETED | 86 | 45 |
NOT COMPLETED | 4 | 1 |
Baseline Characteristics
Arm/Group Title | Arm A | Arm B | Total |
---|---|---|---|
Arm/Group Description | 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. | 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 Participants | 90 | 46 | 136 |
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
Title | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12): Non-inferiority of Arm A to Arm B |
---|---|
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 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 Frame | 12 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 Title | Arm A | Arm B |
---|---|---|
Arm/Group Description | 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. | 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 Participants | 90 | 46 |
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 Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Risk Difference (RD) |
Estimated Value | 4.3 | |
Confidence Interval |
(2-Sided) 95% -3.5 to 12.1 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments | 95% CI was calculated using the normal approximation to the binomial distribution. |
Title | Percentage of Participants in Arm A With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) |
---|---|
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. |
Time Frame | 12 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 Title | Arm A |
---|---|
Arm/Group Description | 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. |
Measure Participants | 90 |
Number (95% Confidence Interval) [percentage of participants] |
97.8
108.7%
|
Title | Percentage of Participants With With On-treatment Virologic Failure |
---|---|
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. 95% CI was calculated using the Wilson score method. |
Time Frame | 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 |
Outcome Measure Data
Analysis Population Description |
---|
All participants who received at least 1 dose of study drug (ITT population). |
Arm/Group Title | Arm A | Arm B |
---|---|---|
Arm/Group Description | 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. | 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 Participants | 90 | 46 |
Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
0
0%
|
Title | Percentage of Participants With Post-Treatment Relapse |
---|---|
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 participants who were been shown to be re-infected. 95% CI was calculated using the Wilson score method. |
Time Frame | From 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 Title | Arm A | Arm B |
---|---|---|
Arm/Group Description | 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. | 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 Participants | 89 | 45 |
Number (95% Confidence Interval) [percentage of participants] |
0
0%
|
4.4
9.6%
|
Adverse Events
Time Frame | Treatment-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 Title | ARM A | ARM B | ||
Arm/Group Description | 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. | 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 A | ARM B | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/90 (0%) | 0/46 (0%) | ||
Serious Adverse Events |
||||
ARM A | ARM B | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 2/90 (2.2%) | 2/46 (4.3%) | ||
Cardiac disorders | ||||
ANGINA UNSTABLE | 1/90 (1.1%) | 0/46 (0%) | ||
Infections and infestations | ||||
PNEUMONIA | 0/90 (0%) | 1/46 (2.2%) | ||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
CASTLEMAN'S DISEASE | 0/90 (0%) | 1/46 (2.2%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
PNEUMOTHORAX SPONTANEOUS | 1/90 (1.1%) | 0/46 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
ARM A | ARM B | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 20/90 (22.2%) | 26/46 (56.5%) | ||
Blood and lymphatic system disorders | ||||
ANAEMIA | 0/90 (0%) | 16/46 (34.8%) | ||
Gastrointestinal disorders | ||||
NAUSEA | 3/90 (3.3%) | 3/46 (6.5%) | ||
STOMATITIS | 1/90 (1.1%) | 3/46 (6.5%) | ||
General disorders | ||||
MALAISE | 5/90 (5.6%) | 4/46 (8.7%) | ||
Infections and infestations | ||||
NASOPHARYNGITIS | 9/90 (10%) | 5/46 (10.9%) | ||
Investigations | ||||
BLOOD BILIRUBIN INCREASED | 1/90 (1.1%) | 7/46 (15.2%) | ||
Metabolism and nutrition disorders | ||||
HYPERURICAEMIA | 0/90 (0%) | 3/46 (6.5%) | ||
Nervous system disorders | ||||
HEADACHE | 6/90 (6.7%) | 1/46 (2.2%) |
Limitations/Caveats
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/Title | Global Medical Services |
---|---|
Organization | AbbVie |
Phone | 800-633-9110 |
abbvieclinicaltrials@abbvie.com |
- M15-828