Genotype 4, HCV, Hepatitis C Infection
Conditions
Keywords
Genotype 4, non-responder, treatment experienced, HCV, naive, relapser, hepatitis infection, compensated cirrhosis, hepatitis c, Cirrhosis, Egypt, null responder, partial responder
Brief summary
This study evaluates the efficacy and safety of ABT-450/r/ABT-267 with RBV in treatment-naive and treatment-experienced HCV GT4 subjects without or with compensated cirrhosis.
Detailed description
Non-cirrhotic subjects were directly enrolled into Arm A. Cirrhotic subjects were randomized to either Arm B (12 weeks of treatment) or Arm C (24 weeks of treatment).
Interventions
DRUG2 DAA
ABT-450/r/ABT-267 tablets
DRUGRBV
Ribavirin tablets
Sponsors
AbbVie
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis C, genotype 4-infection (hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] level greater than 1,000 IU/mL at Screening) * Subjects must meet one of the following: * Treatment-naive: Subject has never received antiviral treatment for HCV infection OR * Treatment Experienced (Prior null responders, Partial responders or Relapsers to pegylated-interferon \[pegIFN\]/RBV); * Females must be post-menopausal, of non-child bearing potential or practicing specific forms of birth control * In substudy 1, demonstrated absence of liver cirrhosis as confirmed by liver biopsy or Fibroscan * In substudy 2, evidence of liver cirrhosis as confirmed by liver biopsy or Fibroscan with Child-Pugh score less than or equal to 6 at Screening and confirmed absence of hepatocellular carcinoma
Exclusion criteria
* Females who are pregnant or breastfeeding * Positive screen for hepatitis B Surface antigen or anti-Human Immunodeficiency virus antibody * HCV genotype performed during screening indicating unable to genotype or co-infection with any other HCV genotype * abnormal laboratory tests * self-reports current drinking more than 2 drinks per day * current enrollment in another investigational study * previous treatment with a direct acting antiviral agent (DAA) containing regimen * In substudy 1, evidence of liver cirrhosis * In substudy 2, evidence of current or past Child-Pugh B or C classification and confirmed presence of hepatocellular carcinoma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Each Treatment Arm | 12 weeks after last dose | SVR12 was defined as 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. |
| Number of Participants With Adverse Events | Screening until 30 days after last dose | 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 reasonable possibility or no reasonable possibility. 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 the first dose of study drug. For more details on adverse events please see the Adverse Event section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Failure in Each Treatment Arm | Up to 12 or 24 weeks after first dose | On-treatment virologic failure was defined as quantifiable HCV RNA throughout the entire treatment period with at least 6 weeks of treatment, confirmed HCV RNA greater than the LLOQ after previously having unquantifiable HCV RNA, or a confirmed increase from nadir of at least one log10 in HCV RNA during treatment. |
| Percentage of Participants With Post-treatment Relapse Within 12 Weeks Following End of Treatment in Each Arm | Up to 12 weeks after first dose | Post-treatment relapse was defined as 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 \< LLOQ at the end of treatment. |
Participant flow
Recruitment details
Safety population: All participants who received at least one dose of study drug.
Participants by arm
| Arm | Count |
|---|---|
| Arm A ABT-450/r/ABT-267 (paritaprevir/ritonavir/ombitasvir; 2 DAA) plus Ribavirin (RBV) for 12 weeks in treatment-naïve and treatment-experienced (with pegylated interferon and ribavirin) participants without cirrhosis. | 100 |
| Arm B ABT-450/r/ABT-267 plus RBV for 12 weeks in treatment-naïve and treatment-experienced (with pegylated interferon and ribavirin) participants with compensated cirrhosis. | 31 |
| Arm C ABT-450/r/ABT-267 plus RBV for 24 weeks in treatment-naïve and treatment-experienced (with pegylated interferon and ribavirin) participants with compensated cirrhosis. | 29 |
| Total | 160 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 1 |
Baseline characteristics
| Characteristic | Arm A | Arm B | Arm C | Total |
|---|---|---|---|---|
| Age, Continuous | 48.6 years STANDARD_DEVIATION 13.14 | 57.3 years STANDARD_DEVIATION 6.48 | 55.8 years STANDARD_DEVIATION 8.02 | 51.6 years STANDARD_DEVIATION 11.91 |
| Sex: Female, Male Female | 30 Participants | 2 Participants | 7 Participants | 39 Participants |
| Sex: Female, Male Male | 70 Participants | 29 Participants | 22 Participants | 121 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 79 / 100 | 24 / 31 | 25 / 29 |
| serious Total, serious adverse events | 2 / 100 | 0 / 31 | 2 / 29 |
Outcome results
Primary
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 reasonable possibility or no reasonable possibility. 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 the first dose of study drug. For more details on adverse events please see the Adverse Event section.
Time frame: Screening until 30 days after last dose
Population: Safety Population: all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A | Number of Participants With Adverse Events | 80 Participants |
| Arm B | Number of Participants With Adverse Events | 26 Participants |
| Arm C | Number of Participants With Adverse Events | 25 Participants |
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Each Treatment Arm
SVR12 was defined as 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 last dose
Population: Intent-to-treat population: all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Each Treatment Arm | 94.0 percentage of participants |
| Arm B | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Each Treatment Arm | 96.8 percentage of participants |
| Arm C | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Each Treatment Arm | 93.1 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Failure in Each Treatment Arm
On-treatment virologic failure was defined as quantifiable HCV RNA throughout the entire treatment period with at least 6 weeks of treatment, confirmed HCV RNA greater than the LLOQ after previously having unquantifiable HCV RNA, or a confirmed increase from nadir of at least one log10 in HCV RNA during treatment.
Time frame: Up to 12 or 24 weeks after first dose
Population: Intent-to-treat population: all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants With On-treatment Virologic Failure in Each Treatment Arm | 1.0 percentage of participants |
| Arm B | Percentage of Participants With On-treatment Virologic Failure in Each Treatment Arm | 3.2 percentage of participants |
| Arm C | Percentage of Participants With On-treatment Virologic Failure in Each Treatment Arm | 3.4 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse Within 12 Weeks Following End of Treatment in Each Arm
Post-treatment relapse was defined as 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 \< LLOQ at the end of treatment.
Time frame: Up to 12 weeks after first dose
Population: Intent-to-treat population: all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm A | Percentage of Participants With Post-treatment Relapse Within 12 Weeks Following End of Treatment in Each Arm | 3.1 percentage of participants |
| Arm B | Percentage of Participants With Post-treatment Relapse Within 12 Weeks Following End of Treatment in Each Arm | 0.0 percentage of participants |
| Arm C | Percentage of Participants With Post-treatment Relapse Within 12 Weeks Following End of Treatment in Each Arm | 0.0 percentage of participants |