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

Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections45 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Hepatitis C Infection HIV Infection

Interventions

Glecaprevir/Pibrentasvir (G/P)DRUG

Fixed-dose combination (FDC) tablets containing 100 mg of glecaprevir and 40 mg of pibrentasvir; administered as 3 tablets orally.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (12)

Ucsd, Avrc Crs (701)

San Diego, California, United States

University of California, San Francisco HIV/AIDS CRS (801)

San Francisco, California, United States

University of Colorado Hospital CRS (6101)

Aurora, Colorado, United States

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

Data from ClinicalTrials.gov

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