Hepatitis C Infection, HIV Infection
Conditions
Keywords
Acute Hepatitis C Infection, Glecaprevir, Pibrentasvir, 4 weeks, Direct-acting antivirals
Brief summary
The purpose of this study was to assess the efficacy of a fixed dose combination (FDC) of glecaprevir/pibrentasvir (G/P) given for 4 weeks for treatment of acute hepatitis C (HCV), with or without HIV-1 coinfection.
Detailed description
The study was conducted in two steps. In Step 1, participants received four weeks of treatment with G/P for acute HCV infection and were then followed 24 weeks post treatment. Participants with HCV recurrence (reinfection, suspected relapse or undefined post-treatment viremia) or HCV virologic failure before or at the Step 1 Week 16 entered Step 2 and were offered HCV re-treatment. The remaining participants were followed in Step 1 for a total of 28 weeks. The study primary and secondary outcome measures pertain to Step 1. In Step 2, participants were re-treated for up to 16 weeks (G/P or alternate regimen through standard of care), and were followed for 24 weeks post treatment. This post-treatment follow-up included a visit for the determination of HCV sustained virologic response (SVR12) after re-treatment. All summaries of data captured from Step 2 are pooled across HCV re-treatment regimens, as specified in the Statistical Analysis Plan. In Step 1, study visits were scheduled at study entry, weeks 1 and 2 (on-treatment), week 4 (treatment discontinuation), and weeks 8, 12, 16 and 28 (post-treatment follow-up). In Step 2, participants had study visits during the re-treatment period, where the number of visits depended on the re-treatment regimen, and at weeks 12 and 24 post treatment. Study visits included physical examinations, clinical assessments, blood and urine collection, questionnaires, and HCV re-infection prevention counseling.
Interventions
DRUGGlecaprevir/Pibrentasvir (G/P)
Fixed-dose combination (FDC) tablets containing 100 mg of glecaprevir and 40 mg of pibrentasvir; administered as 3 tablets orally.
Sponsors
AbbVie
National Institute of Allergy and Infectious Diseases (NIAID)
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
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
* Acute HCV infection (or reinfection) within 24 weeks prior to entry * Detectable HCV RNA at the screening visit
Exclusion criteria
* Any HCV treatment during the current acute HCV infection episode * Known preexisting cirrhosis * Acute HIV-1 infection * Presence of active or acute AIDS-defining opportunistic infections, active serious infection (other than HIV-1 or HCV), active hepatitis B virus (HBV) or active hepatitis A virus (HAV) * Chronic use of systemically administered immunosuppressive agents * History of solid organ transplantation * History of conditions that could interfere with the absorption of the study drug * Concurrent use of prohibited medications * Known hypersensitivity to glecaprevir or pibrentasvir, the metabolites, or parts of the formulation * Females who are pregnant or breastfeeding * Males with pregnant female partner
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment Discontinuation (SVR12) | Week 16 (12 weeks post study treatment) | SVR12 defined as unquantifiable HCV RNA (less than the lower limit of quantification \[LLOQ\], target detected \[TD\] or target not detected \[TND\]) at study visit 12 weeks post treatment (Week 16). If a participant did not have HCV RNA measurement at Week 16, the participant was considered as SVR12 failure, unless there were preceding and subsequent HCV RNA measurements that were both LLOQ (either TD or TND). |
| Percentage of Participants Who Experienced Adverse Events (AEs) | From study entry to Week 8 (4 weeks post study treatment) | Study protocol required reporting of (1) AEs Grade greater than or equal to 2, (2) AEs that led to a change in study treatment regardless of grade and (3) AEs meeting ICH definition of serious AE (SAE) or Expedited AE (EAE) reporting requirement. DAIDS AE Grading Table (V2.1) and DAIDS EAE Manual (V2.0) were used. |
| Number of Participants Who Completed 4 Weeks of Treatment Without Discontinuation Due to AEs | From study entry to Week 4 | Number of participants who completed 4 weeks of treatment without discontinuation due to AEs |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With HCV RNA Less Than LLOQ | Weeks 1, 2, 4, 8, 12, 28 | Percentage of participants with HCV RNA less than LLOQ (TD or TND). Given the substantial amount of missing data due to the SARS-CoV-2 pandemic, the planned analysis of 90% confidence intervals for the percentage of participants with HCV RNA \<LLOQ at study visits could not be conducted in a meaningful way. |
| Number of Participants With HCV Virologic Failure | From Week 1 to Week 16 | Virologic failure defined as failure to achieve unquantifiable HCV RNA or confirmed increase in HCV RNA greater than 1 log10 from on-treatment nadir |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants by HCV Re-Treatment Regimen in Step 2 | At Step 2 entry (median time of Step 2 entry was at 21 weeks after study entry. | Participants who experienced HCV re-infection, suspected relapse, virologic failure, or undefined post-treatment viremia in Step 1 were offered to enter Step 2 for re-treatment. HCV re-treatment regimens may have included various regimens including study-provided G/P and alternate regimens through clinical care. This outcome measure is used to report the re-treatment regimens observed in Step 2. |
Countries
Brazil, United States
Participant flow
Recruitment details
Participants were enrolled from November 2019 to January 2023.
Participants by arm
| Arm | Count |
|---|---|
| Glecaprevir/Pibrentasvir (G/P) G/P FDC tablets to be taken orally once daily for 4 weeks, followed by 24 weeks of observation (Step 1). | 45 |
| Total | 45 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Step 1 (4-week G/P + 24-week Follow-up) | Lost to Follow-up | 2 |
| Step 1 (4-week G/P + 24-week Follow-up) | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Age, Continuous | 36 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| HCV genotype Genotype 1 | 32 Participants |
| HCV genotype Genotype 2 | 2 Participants |
| HCV genotype Genotype 3 | 1 Participants |
| HCV genotype Genotype 4 | 5 Participants |
| HCV genotype Indeterminate | 1 Participants |
| HCV genotype Not detected | 3 Participants |
| HCV genotype Unable to result | 1 Participants |
| HCV history No history of HCV | 38 Participants |
| HCV history Previous HCV | 7 Participants |
| HCV RNA | 5.25 log10 IU/mL |
| HIV-1 status HIV-1 present | 23 Participants |
| HIV-1 status No HIV-1 | 22 Participants |
| Injection drug use Former | 12 Participants |
| Injection drug use Never | 33 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants |
| Race/Ethnicity, Customized Black or African American | 12 Participants |
| Race/Ethnicity, Customized Other | 4 Participants |
| Race/Ethnicity, Customized Unknown | 3 Participants |
| Race/Ethnicity, Customized White | 23 Participants |
| Region of Enrollment Brazil | 14 Participants |
| Region of Enrollment United States | 31 Participants |
| Sex: Female, Male Female | 1 Participants |
| Sex: Female, Male Male | 44 Participants |
| Sex/Gender, Customized Female | 1 Participants |
| Sex/Gender, Customized Male | 43 Participants |
| Sex/Gender, Customized Non-binary | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 45 | 4 / 4 |
| other Total, other adverse events | 32 / 45 | 4 / 4 |
| serious Total, serious adverse events | 4 / 45 | 1 / 4 |
Outcome results
Primary
Number of Participants Who Completed 4 Weeks of Treatment Without Discontinuation Due to AEs
Number of participants who completed 4 weeks of treatment without discontinuation due to AEs
Time frame: From study entry to Week 4
Population: All eligible participants who initiated study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glecaprevir/Pibrentasvir (G/P) | Number of Participants Who Completed 4 Weeks of Treatment Without Discontinuation Due to AEs | 45 Participants |
Primary
Percentage of Participants Who Experienced Adverse Events (AEs)
Study protocol required reporting of (1) AEs Grade greater than or equal to 2, (2) AEs that led to a change in study treatment regardless of grade and (3) AEs meeting ICH definition of serious AE (SAE) or Expedited AE (EAE) reporting requirement. DAIDS AE Grading Table (V2.1) and DAIDS EAE Manual (V2.0) were used.
Time frame: From study entry to Week 8 (4 weeks post study treatment)
Population: All eligible participants who initiated study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir (G/P) | Percentage of Participants Who Experienced Adverse Events (AEs) | 60.0 percentage of participants |
Primary
Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment Discontinuation (SVR12)
SVR12 defined as unquantifiable HCV RNA (less than the lower limit of quantification \[LLOQ\], target detected \[TD\] or target not detected \[TND\]) at study visit 12 weeks post treatment (Week 16). If a participant did not have HCV RNA measurement at Week 16, the participant was considered as SVR12 failure, unless there were preceding and subsequent HCV RNA measurements that were both LLOQ (either TD or TND).
Time frame: Week 16 (12 weeks post study treatment)
Population: All eligible participants who initiated study treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Glecaprevir/Pibrentasvir (G/P) | Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment Discontinuation (SVR12) | 84.4 percentage of participants |
Secondary
Number of Participants With HCV Virologic Failure
Virologic failure defined as failure to achieve unquantifiable HCV RNA or confirmed increase in HCV RNA greater than 1 log10 from on-treatment nadir
Time frame: From Week 1 to Week 16
Population: All eligible participants who initiated study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Glecaprevir/Pibrentasvir (G/P) | Number of Participants With HCV Virologic Failure | 6 Participants |
Secondary
Percentage of Participants With HCV RNA Less Than LLOQ
Percentage of participants with HCV RNA less than LLOQ (TD or TND). Given the substantial amount of missing data due to the SARS-CoV-2 pandemic, the planned analysis of 90% confidence intervals for the percentage of participants with HCV RNA \<LLOQ at study visits could not be conducted in a meaningful way.
Time frame: Weeks 1, 2, 4, 8, 12, 28
Population: All eligible participants who initiated study treatment with HCV RNA data available at the given visit. The study conduct overlapped with the COVID-19 pandemic. At the beginning of the COVID-19 pandemic, Week 16 visit was prioritized; other study visits may have occurred remotely without HCV RNA collection, due to COVID-related restrictions at the sites.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Glecaprevir/Pibrentasvir (G/P) | Percentage of Participants With HCV RNA Less Than LLOQ | Week 1 HCV RNA <LLOQ | 51.4 percentage of participants |
| Glecaprevir/Pibrentasvir (G/P) | Percentage of Participants With HCV RNA Less Than LLOQ | Week 2 HCV RNA <LLOQ | 70.7 percentage of participants |
| Glecaprevir/Pibrentasvir (G/P) | Percentage of Participants With HCV RNA Less Than LLOQ | Week 4 HCV RNA <LLOQ | 97.6 percentage of participants |
| Glecaprevir/Pibrentasvir (G/P) | Percentage of Participants With HCV RNA Less Than LLOQ | Week 8 HCV RNA <LLOQ | 97.2 percentage of participants |
| Glecaprevir/Pibrentasvir (G/P) | Percentage of Participants With HCV RNA Less Than LLOQ | Week 12 HCV RNA <LLOQ | 88.2 percentage of participants |
| Glecaprevir/Pibrentasvir (G/P) | Percentage of Participants With HCV RNA Less Than LLOQ | Week 28 HCV RNA <LLOQ | 81.0 percentage of participants |
Other Pre-specified
Number of Participants by HCV Re-Treatment Regimen in Step 2
Participants who experienced HCV re-infection, suspected relapse, virologic failure, or undefined post-treatment viremia in Step 1 were offered to enter Step 2 for re-treatment. HCV re-treatment regimens may have included various regimens including study-provided G/P and alternate regimens through clinical care. This outcome measure is used to report the re-treatment regimens observed in Step 2.
Time frame: At Step 2 entry (median time of Step 2 entry was at 21 weeks after study entry.
Population: All participants who entered Step 2 for HCV re-treatment.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Glecaprevir/Pibrentasvir (G/P) | Number of Participants by HCV Re-Treatment Regimen in Step 2 | Glecaprevir/pibrentasvir | 3 Participants |
| Glecaprevir/Pibrentasvir (G/P) | Number of Participants by HCV Re-Treatment Regimen in Step 2 | Sofosbuvir/velpatasvir/voxilaprevir | 1 Participants |