A Phase 2 interventional study of Glecaprevir/Pibrentasvir (G/P) in Hepatitis C Infection and HIV Infection, sponsored by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections. Completed at 12 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-07-11.
Sponsored by Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections · Phase 2, Interventional, and Treatment
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.
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.
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This study's enrollment of 45 is below the median of 120 across 4,200 interventional studies indexed under Infections.
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Of its 7 completed or terminated interventional studies of FDA-regulated products, 6 (86%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria
Participants were assigned to receive G/P FDC tablets to be taken orally once daily for 4 weeks (Step 1). 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 G/P FDC tablets orally once daily for 8-16 weeks, or alternate regimens through clinical care.
Drug: Glecaprevir/Pibrentasvir (G/P)
Fixed-dose combination (FDC) tablets containing 100 mg of glecaprevir and 40 mg of pibrentasvir; administered as 3 tablets orally.
Also known as: Mavyret
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)
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)
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
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
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
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.
Participants were enrolled from November 2019 to January 2023.
| Milestone | Glecaprevir/Pibrentasvir (G/P) Followed by Re-treatment, as Needed |
|---|---|
| Started | 45 |
| Initiated study treatment | 45 |
| Completed 16 weeks | 44 |
| Completed | 42 |
| Not completed | 3 |
| Withdrew: Lost to follow-up | 2 |
| Withdrew: Withdrawal by subject | 1 |
| Milestone | Glecaprevir/Pibrentasvir (G/P) Followed by Re-treatment, as Needed |
|---|---|
| Started | 4 |
| Completed | 3 |
| Not completed | 1 |
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 | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Percentage of Participants With Sustained Virologic Response at 12 Weeks Post Treatment Discontinuation (SVR12) | 84.4 (73.6 to 91.3) |
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.
| percentage of participants | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Percentage of Participants Who Experienced Adverse Events (AEs) | 60.0 (45.5 to 73.0) |
Number of participants who completed 4 weeks of treatment without discontinuation due to AEs
| Participants | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Number of Participants Who Completed 4 Weeks of Treatment Without Discontinuation Due to AEs | 45 |
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.
| percentage of participants | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Week 1 HCV RNA <LLOQ | 51.4 |
| Week 2 HCV RNA <LLOQ | 70.7 |
| Week 4 HCV RNA <LLOQ | 97.6 |
| Week 8 HCV RNA <LLOQ | 97.2 |
| Week 12 HCV RNA <LLOQ | 88.2 |
| Week 28 HCV RNA <LLOQ | 81.0 |
Virologic failure defined as failure to achieve unquantifiable HCV RNA or confirmed increase in HCV RNA greater than 1 log10 from on-treatment nadir
| Participants | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Number of Participants With HCV Virologic Failure | 6 |
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.
| Participants | HCV Re-Treatment Regimens |
|---|---|
| Glecaprevir/pibrentasvir | 3 |
| Sofosbuvir/velpatasvir/voxilaprevir | 1 |
Collected over Step 1: From study entry to study completion or Step 2 entry or premature study discontinuation (median time in Step 1 was 28 weeks). Step 2: From Step 2 entry to study completion or premature discontinuation (median time in Step 2 was 21 weeks).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Glecaprevir/Pibrentasvir (G/P) | 0/45 (0%) | 4/45 (8.9%) | 32/45 (71.1%) |
| HCV Re-Treatment Regimens | 4/4 (100%) | 1/4 (25%) | 4/4 (100%) |
| Event | Glecaprevir/Pibrentasvir (G/P) | HCV Re-Treatment Regimens |
|---|---|---|
| HaematuriaRenal and urinary disorders | 0/45 | 1/4 |
| OverdoseInjury, poisoning and procedural complications | 1/45 | 0/4 |
| Carotid artery diseaseNervous system disorders | 1/45 | 0/4 |
| AnxietyPsychiatric disorders | 1/45 | 0/4 |
| Mental status changesPsychiatric disorders | 1/45 | 0/4 |
| Event | Glecaprevir/Pibrentasvir (G/P) | HCV Re-Treatment Regimens |
|---|---|---|
| ConstipationGastrointestinal disorders | 1/45 | 1/4 |
| ProctalgiaGastrointestinal disorders | 1/45 | 1/4 |
| FatigueGeneral disorders | 0/45 | 1/4 |
| CellulitisInfections and infestations | 0/45 | 1/4 |
| Oropharyngeal gonococcal infectionInfections and infestations | 1/45 | 1/4 |
| Proctitis gonococcalInfections and infestations | 1/45 | 1/4 |
| Proctitis herpesInfections and infestations | 0/45 | 1/4 |
| Secondary syphilisInfections and infestations | 0/45 | 1/4 |
| Skin lacerationInjury, poisoning and procedural complications | 2/45 | 1/4 |
| Alanine aminotransferase increasedInvestigations | 9/45 | 1/4 |
All eligible participants who initiated study treatment
| Age, Continuous(years) | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Median | 36 (29 to 43) |
| Sex/Gender, Customized(Participants) | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Female | 1 |
| Male | 43 |
| Non-binary | 1 |
| Sex: Female, Male(Participants) | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Female | 1 |
| Male | 44 |
| Ethnicity (NIH/OMB)(Participants) | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Hispanic or Latino | 14 |
| Not Hispanic or Latino | 30 |
| Unknown or Not Reported | 1 |
| Race/Ethnicity, Customized(Participants) | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Asian | 3 |
| Black or African American | 12 |
| White | 23 |
| Other | 4 |
| Unknown | 3 |
| Region of Enrollment(Participants) | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| United States | 31 |
| Brazil | 14 |
| HCV history(Participants) | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| No history of HCV | 38 |
| Previous HCV | 7 |
| HCV genotype(Participants) | Glecaprevir/Pibrentasvir (G/P) |
|---|---|
| Genotype 1 | 32 |
| Genotype 2 | 2 |
| Genotype 3 | 1 |
| Genotype 4 | 5 |
| Indeterminate | 1 |
| Not detected | 3 |
| Unable to result | 1 |
3 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — Individual participant data that underlie results in the publication, after deidentification.
Supporting information: Study protocol, Sap
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Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections