Hepatitis C Virus (HCV)
Conditions
Keywords
hepatitis C infection, hepatitis C, severe kidney disease, chronic kidney disease, Genotype 1a, Genotype 4, treatment experienced, interferon, IFN, pegIFN
Brief summary
This study evaluates the efficacy and safety of ombitasvir/paritaprevir/ritonavir with or without dasabuvir in adults with hepatitis C virus (HCV) genotype 1a (GT1a) or genotype 4 (GT4) infection and with severe kidney impairment or end-stage kidney disease.
Interventions
Tablet; ombitasvir coformulated with paritaprevir and ritonavir, dasabuvir tablet
Tablet; ombitasvir coformulated with paritaprevir and ritonavir
Sponsors
AbbVie
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Chronic hepatitis C virus (HCV) genotype 1a (GT1a) infection or genotype 4 (GT4) infection (HCV RNA level greater than 1,000 IU/mL at Screening). * Females must be post-menopausal, of non-child bearing potential or practicing specific forms of birth control. * Chronic kidney disease stage 4 or stage 5.
Exclusion criteria
* Females who are pregnant or breastfeeding * Positive test result for Hepatitis B surface antigen (HBsAg) or anti-human immunodeficiency virus antibody (HIV Ab) * HCV genotype performed during screening unable to genotype or co-infection with any other HCV genotype, no mixed genotypes. * Abnormal laboratory tests * Current enrollment in another investigational study * Prior treatment with a direct acting antiviral agent (DAA) containing regimen with the exception of interferon or pegylated interferon with or without ribavirin * Current treatment with a direct acting antiviral agent (DAA) containing regimen * Any evidence of liver cirrhosis or liver cancer
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants 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. Participants with missing data after backward imputation were imputed as nonresponders. |
| Number of Participants With Adverse Events | Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 16 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 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 from first dose of study drug until 30 days after the last dose. For more details on AEs please see the Adverse Event section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Failure | 12 weeks | On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during treatment or confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment with at least 6 weeks of treatment. |
| 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. |
Participant flow
Pre-assignment details
This study included a 42-day screening period.
Participants by arm
| Arm | Count |
|---|---|
| HCV GT1a (3-DAA) Participants with hepatitis C virus (HCV) genotype 1a (GT1a) infection received 3-direct-acting antiviral agent (3-DAA: ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 mg once daily\] and dasabuvir \[250 mg twice daily\]) for 12 weeks. | 13 |
| HCV GT4 (2-DAA) Participants with hepatitis C virus (HCV) genotype 4 (GT4) infection received 2-direct-acting antiviral agent (2-DAA: ombitasvir/paritaprevir/ritonavir \[25 mg/150 mg/100 mg once daily\]) for 12 weeks. | 5 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrew Consent | 0 | 1 |
Baseline characteristics
| Characteristic | HCV GT1a (3-DAA) | HCV GT4 (2-DAA) | Total |
|---|---|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 10 | 53.6 years STANDARD_DEVIATION 14.08 | 54.5 years STANDARD_DEVIATION 10.84 |
| Sex: Female, Male Female | 4 Participants | 2 Participants | 6 Participants |
| Sex: Female, Male Male | 9 Participants | 3 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 13 / 13 | 5 / 5 |
| serious Total, serious adverse events | 3 / 13 | 1 / 5 |
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 from first dose of study drug until 30 days after the last dose. For more details on AEs please see the Adverse Event section.
Time frame: Treatment-emergent adverse events (TEAEs) and serious adverse events (TESAEs) were collected from first dose of study drug until 30 days after the last dose of study drug (up to 16 weeks)
Population: Safety population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| HCV GT1a (3-DAA) | Number of Participants With Adverse Events | Any TEAE | 13 Participants |
| HCV GT1a (3-DAA) | Number of Participants With Adverse Events | Any TESAE | 3 Participants |
| HCV GT4 (2-DAA) | Number of Participants With Adverse Events | Any TEAE | 5 Participants |
| HCV GT4 (2-DAA) | Number of Participants With Adverse Events | Any TESAE | 1 Participants |
Primary
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)
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. Participants with missing data after backward imputation were imputed as nonresponders.
Time frame: 12 weeks after the last actual dose of study drug
Population: Intent-to-treat (ITT) population: All participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCV GT1a (3-DAA) | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 100 percentage of participants |
| HCV GT4 (2-DAA) | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 80.0 percentage of participants |
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed HCV RNA ≥ LLOQ after HCV RNA \< LLOQ during treatment or confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment with at least 6 weeks of treatment.
Time frame: 12 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCV GT1a (3-DAA) | Percentage of Participants With On-treatment Virologic Failure | 0.0 percentage of participants |
| HCV GT4 (2-DAA) | Percentage of Participants With On-treatment Virologic Failure | 0.0 percentage of participants |
Secondary
Percentage of Participants With Post-treatment Relapse
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.
Time frame: From the end of treatment through 12 weeks after the last dose of study drug
Population: All participants who received at least 1 dose of study drug, completed treatment, and had HCV RNA \<LLOQ at the final treatment visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HCV GT1a (3-DAA) | Percentage of Participants With Post-treatment Relapse | 0.0 percentage of participants |
| HCV GT4 (2-DAA) | Percentage of Participants With Post-treatment Relapse | 0.0 percentage of participants |