Chronic Hepatitis C
Conditions
Keywords
Hepatitis C Virus (HCV), Hepatitis C Genotype 1, Chronic Hepatitis C, HCV
Brief summary
A study to evaluate the safety and effect of treatment with experimental antiviral drugs in combination with peginterferon alpha-2a and ribavirin in people with hepatitis C virus who did not respond to treatment in a previous AbbVie/Abbott combination study.
Interventions
Sponsors
AbbVie (prior sponsor, Abbott)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 71 Years
Healthy volunteers
No
Inclusion criteria
Main Inclusion: To be enrolled in this protocol, subjects must meet all of the following inclusion criteria: * Subject must have experienced virologic failure as defined in a previous AbbVie/Abbott direct-acting antiviral (DAA) combination trial. * Female subjects of childbearing potential must be willing to use two effective forms of birth control (not including oral contraceptives or contraceptives containing ethinyl estradiol) while receiving study drug and for 7 months (or per local ribavirin label) after stopping study drug. * Males must be surgically sterile or have male partners only or agree to practice two effective forms of birth control throughout the course of the study, starting with Study Day 1 and for 7 months (or per local ribavirin label) after the last dose of study drug, unless abstinent from sexual intercourse. * Subject must be considered an appropriate candidate for peginterferon (pegIFN) alpha-2a, ribavirin (RBV), ABT-450/ritonavir (r) and ABT-267 therapy in the opinion of the investigator. * Subject is infected with hepatitis C virus (HCV) genotype 1 at screening. Subjects diagnosed with cirrhosis must also meet the following criteria: * Compensated cirrhosis defined as Child-Pugh score of ≤ 6 at Screening. * Absence of hepatocellular carcinoma based on a negative ultrasound, computed tomography (CT) scan or magnetic resonance imaging (MRI) performed within 3 months prior to Screening or during the Screening period.
Exclusion criteria
* In subjects with a prior null or partial response to pegIFN/RBV treatment at any time prior to pre-screening for this study or any prior failure with pegIFN/RBV plus telaprevir, the presence of variants relative to the appropriate prototypic reference sequence (H77 for 1a or Con1 for 1b) at any of the following positions: NS3 155, 156, or 168; or NS5A 28, 29, 30, 31, 32, 58, or 93. * Females who are pregnant or plan to become pregnant, or breast-feeding, or males whose partners are pregnant or planning to become pregnant within 7 months (or per local RBV label) after their last dose of RBV. * Use of known strong inducers (e.g., phenobarbital, rifampin, carbamazepine, St. John's Wort) of Cytochrome P450 3A (CYP3A) within 2 weeks prior to study drug administration. * Use of any medications contraindicated for use with pegIFN alpha-2a, RBV or ritonavir within 2 weeks prior to study drug administration. Prior to entering the study, subjects must be able to safely discontinue the contraindicated medication or switch to an acceptable alternative under supervision of the investigator. * Discontinuation of antiviral therapy due to intolerance or a DAA- or RBV-associated adverse event in a previous AbbVie/Abbott DAA combination study. Subjects with compensated cirrhosis must also not meet the following criteria: * Any current or past clinical evidence of Child-Pugh B or C Classification or clinical history of liver decompensation such as ascites (noted on physical exam), variceal bleeding or hepatic encephalopathy. * Serum Alpha-Fetoprotein (sAFP) \> 100 ng/mL at Screening. * A screening ultrasound suspicious for hepatocellular carcinoma and confirmed with a subsequent CT scan or MRI during the screening period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 12 weeks after last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV); approximately 36 weeks after subject's initial dose of study drug in Substudy 1 | SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than lower limit of quantitation \[LLOQ\] 12 weeks after the last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Virologic Response 24 Weeks Post Treatment (SVR24) | 24 weeks after last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV); approximately 48 weeks after subject's initial dose of study drug in Substudy 1 | SVR24 was defined as HCV RNA level less than the LLOQ 24 weeks after the last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV). |
| Percentage of Participants With Extended Rapid Virologic Response (eRVR) | Treatment weeks 4 through 12 of Substudy 1 (DAAs plus pegIFN alpha-2a and RBV) | eRVR was defined as HCV RNA level \< LLOQ at Substudy 1 treatment weeks 4 through 12 without a confirmed HCV RNA \>= LLOQ |
| Number of Participants With Adverse Events | From first dose of study drug through 30 days after last dose of study drug (DAAs plus pegIFN alpha-2a and RBV) (up to 28 weeks). | An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after initiation of study drug through 30 days post-DAA dosing. For more details on AEs, see the AE section. |
Participant flow
Pre-assignment details
The study included a 42-day screening period.
Participants by arm
| Arm | Count |
|---|---|
| 2-DAA + PegIFN/RBV 2-direct-acting antiviral (2-DAA: ABT-450 \[paritaprevir\] 200 mg once daily \[QD\], ritonavir 100 mg QD, ABT-267 \[ombitasvir\] 25 mg QD) plus pegylated interferon alpha-2a (pegIFN) 180 mcg once weekly and Ribavirin (RBV) weight-based dosing, 1000 to 1200 mg divided twice daily (BID) for 24 weeks and followed by pegIFN and RBV alone for an additional 24 weeks. | 32 |
| Total | 32 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Withdrawal by Subject | 3 |
Baseline characteristics
| Characteristic | 2-DAA + PegIFN/RBV |
|---|---|
| Age, Continuous | 51.4 years STANDARD_DEVIATION 9.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 32 |
| other Total, other adverse events | 28 / 32 |
| serious Total, serious adverse events | 1 / 32 |
Outcome results
Primary
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Treatment (SVR12)
SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than lower limit of quantitation \[LLOQ\] 12 weeks after the last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV).
Time frame: 12 weeks after last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV); approximately 36 weeks after subject's initial dose of study drug in Substudy 1
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2-DAA + PegIFN/RBV | Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Treatment (SVR12) | 81.3 percentage of participants |
Secondary
Number of Participants With Adverse Events
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. The investigator assessed the relationship of each event to the use of study drug as either probably related, possibly related, probably not related or not related. A serious adverse event (SAE) is an event that results in death, is life-threatening, requires or prolongs hospitalization, results in a congenital anomaly, persistent or significant disability/incapacity or is an important medical event that, based on medical judgment, may jeopardize the subject and may require medical or surgical intervention to prevent any of the outcomes listed above. Treatment-emergent events (TEAEs/TESAEs) are defined as any event that began or worsened in severity after initiation of study drug through 30 days post-DAA dosing. For more details on AEs, see the AE section.
Time frame: From first dose of study drug through 30 days after last dose of study drug (DAAs plus pegIFN alpha-2a and RBV) (up to 28 weeks).
Population: Safety population (all subjects who received at least 1 dose of study drug)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| 2-DAA + PegIFN/RBV | Number of Participants With Adverse Events | 2-DAA TEAE | 29 participants |
| 2-DAA + PegIFN/RBV | Number of Participants With Adverse Events | 2-DAA TESAE | 1 participants |
Secondary
Percentage of Participants Achieving Virologic Response 24 Weeks Post Treatment (SVR24)
SVR24 was defined as HCV RNA level less than the LLOQ 24 weeks after the last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV).
Time frame: 24 weeks after last dose of study drugs (DAAs plus pegIFN alpha-2a and RBV); approximately 48 weeks after subject's initial dose of study drug in Substudy 1
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2-DAA + PegIFN/RBV | Percentage of Participants Achieving Virologic Response 24 Weeks Post Treatment (SVR24) | 78.1 percentage of participants |
Secondary
Percentage of Participants With Extended Rapid Virologic Response (eRVR)
eRVR was defined as HCV RNA level \< LLOQ at Substudy 1 treatment weeks 4 through 12 without a confirmed HCV RNA \>= LLOQ
Time frame: Treatment weeks 4 through 12 of Substudy 1 (DAAs plus pegIFN alpha-2a and RBV)
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| 2-DAA + PegIFN/RBV | Percentage of Participants With Extended Rapid Virologic Response (eRVR) | 87.5 percentage of participants |