Chronic Hepatitis C, HCV, Hepatitis C Virus
Conditions
Keywords
HCV Treatment Experienced, Hepatitis C, HCV Genotype 3, Without cirrhosis, Non-cirrhotic, HCV Genotype 2, Renal Transplant, HCV Treatment Naive, Post transplant, HCV Genotype 6, Liver Transplant, HCV Genotype 5, HCV Genotype 4, Kidney Transplant, HCV Genotype 1
Brief summary
The purpose of this study is to assess the safety and efficacy of 12 weeks of treatment of ABT-493/ABT-530 (glecaprevir/pibrentasvir) in adults who are post primary orthotopic liver or renal transplant with chronic hepatitis C virus (HCV) infection.
Interventions
Tablet; glecaprevir coformulated with pibrentasvir
Sponsors
AbbVie
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female, at least 18 years of age at time of screening. * Screening laboratory result indicating hepatitis C virus (HCV) genotype 1-6 (GT1-6) infection. * Subject is a recipient of a cadaveric or living donor liver transplant which was a consequence of HCV infection at least 3 months prior to screening Or subject received a cadaveric or living donor kidney at least 3 months before screening. * Subjects must be documented as non-cirrhotic. * Subject is currently taking a stable immunosuppression regimen based on tacrolimus, sirolimus, everolimus, mycophenolate mofetil (MMF), mycophenolic acid, azathioprine, and/or cyclosporine.
Exclusion criteria
* Female subject who is pregnant, breastfeeding or is considering becoming pregnant during the study or for approximately 30 days after the last dose of study drug. * Clinical history of fibrosing cholestatic hepatitis post-transplant. * Re-transplantation of the liver or kidney. * Steroid resistant rejection of the transplanted liver or kidney, or a history of rejection treated with high dose steroid within 3 months of screening. * History of post-transplant complications related to hepatic or renal vasculature.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 12 weeks after the last dose of study drug (up to 24 weeks) | 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 noninferiority of the percentage of participants who achieved SVR12 compared with the historical SVR12 rate for the current standard of care regimens (sofosbuvir \[SOF\]/ledipasvir \[LDV\] + ribavirin \[RBV\] OR SOF + daclatasvir \[DCV\] + RBV). Participants with missing data after backward imputation were counted as non-responders. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With On-treatment Virologic Failure | Up to 12 weeks | On-treatment virologic failure was defined as confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in 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. |
| Percentage of Participants With Post-treatment Relapse | From the end of treatment through 12 weeks after the last dose of study drug (up to 12 weeks) | 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
The study included a 36-day screening period.
Participants by arm
| Arm | Count |
|---|---|
| Glecaprevir/Pibrentasvir Glecaprevir/pibrentasvir (300 mg/120 mg) coformulated once daily (QD) for 12 weeks. | 100 |
| Total | 100 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Other | 1 |
Baseline characteristics
| Characteristic | Glecaprevir/Pibrentasvir |
|---|---|
| Age, Continuous | 59.19 years STANDARD_DEVIATION 7.68 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 17 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 83 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 3 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 78 Participants |
| Sex: Female, Male Female | 25 Participants |
| Sex: Female, Male Male | 75 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 100 |
| other Total, other adverse events | 67 / 100 |
| serious Total, serious adverse events | 8 / 100 |
Outcome results
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. The primary efficacy endpoint was noninferiority of the percentage of participants who achieved SVR12 compared with the historical SVR12 rate for the current standard of care regimens (sofosbuvir \[SOF\]/ledipasvir \[LDV\] + ribavirin \[RBV\] OR SOF + daclatasvir \[DCV\] + RBV). Participants with missing data after backward imputation were counted as non-responders.
Time frame: 12 weeks after the last dose of study drug (up to 24 weeks)
Population: Intent-to-treat (ITT) population: all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) | 98 percentage of participants |
Comparison: Based on a 2-sided significance level of 0.05 and an underlying rate of ≥96%, 90 participants provides \>90% power to demonstrate noninferiority of the regimen to the historical rate for current standard of care regimens (SOF/LDV + RBV OR SOF + DCV + RBV) (94%) (based on the normal approximation of a single binomial proportion in a one-sample test for superiority).95% CI: [95.3, 100]
Secondary
Percentage of Participants With On-treatment Virologic Failure
On-treatment virologic failure was defined as confirmed increase of \> 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in 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.
Time frame: Up to 12 weeks
Population: ITT population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants With On-treatment Virologic Failure | 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 (up to 12 weeks)
Population: All participants who received at least 1 dose of study drug, completed treatment, had HCV RNA \<LLOQ at the final treatment visit, and had post-treatment data available, excluding reinfection.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir | Percentage of Participants With Post-treatment Relapse | 1 percentage of participants |