Glecaprevir/Pibrentasvir Fixed-dose Combination Treatment for Acute Hepatitis C Virus Infection

Phase 2

Completed

Lead Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections

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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Glecaprevir/Pibrentasvir (G/P)	Glecaprevir/Pibrentasvir (G/P)	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Locations (12): Massachusetts General Hospital ACTG CRS (101)
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Boston, Massachusetts, United States
Columbia Physicians and Surgeons CRS (30329)
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New York, New York, United States
Weill Cornell Chelsea CRS (7804)
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New York, New York, United States
Johns Hopkins Adult AIDS CRS
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Baltimore, Maryland, United States
Instituto de Pesquisa Clinica Evandro Chagas (12101)
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Rio de Janeiro, Brazil
Weill Cornell Upton CRS (7803)
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New York, New York, United States
Whitman-Walker Institute, Inc. CRS (31791)
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Washington, District of Columbia, United States
University of Colorado Hospital CRS (6101)
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Aurora, Colorado, United States
Ucsd, Avrc Crs (701)
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San Diego, California, United States
Unc Aids Crs (3201)
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Chapel Hill, North Carolina, United States
University of Washington AIDS CRS (1401)
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Seattle, Washington, United States
University of California, San Francisco HIV/AIDS CRS (801)
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San Francisco, California, United States