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

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of a fixed dose combination (FDC) of glecaprevir/pibrentasvir (G/P) given for 4 weeks in acute hepatitis C (HCV)-infected participants, with or without HIV-1 coinfection.

Detailed Description
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The study will be conducted in two steps. In Step 1, participants will receive four weeks of treatment with G/P for acute HCV infection and 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/SVR12 (sustained virologic response 12 weeks post-treatment) visit may enter Step 2 for re-treatment. The remaining participants complete the study at Week 28 of Step 1. The study primary and secondary outcome measures pertain to Step 1. In Step 2, participants will be re-treated with G/P with or without ribavirin (RBV) for up to 16 weeks, and followed for 24 weeks post treatment. Post-treatment follow-up for Step 2 will include visits for SVR12 determination after re-treatment. In Step 1, study visits are 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 will have study visits during the re-treatment period, where the number of visits depends on the re-treatment, and visits at 12 and 24 weeks post treatment. Study visits may include physical examinations, clinical assessments, blood and urine collection, questionnaires, and HCV re-infection prevention counseling.

Official Title
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Glecaprevir/Pibrentasvir Fixed-dose Combination Treatment for Acute Hepatitis C Virus Infection (PURGE-C)

Conditions
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Hepatitis C Infection, HIV Infection

Intervention / Treatment
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* Drug: Glecaprevir/Pibrentasvir (G/P)
* Drug: Ribavirin (RBV)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glecaprevir/Pibrentasvir (G/P)<br>In Step 1, participants will receive G/P FDC tablets to be taken orally once daily for 4 weeks. Any participant who experiences viral re-infection, suspected relapse, virologic failure, or undefined post-treatment HCV viremia may enter Step 2. In Step 2, participants may receive G/P FDC tablets orally once daily for 8-16 weeks. Some participants may also receive ribavirin (RBV) tablets orally twice daily. Alternate regimens are allowed in Step 2. | Drug: Glecaprevir/Pibrentasvir (G/P)<br>* Fixed-dose combination (FDC) tablets containing 100 mg of glecaprevir and 40 mg of pibrentasvir; administered as 3 tablets orally.<br>Drug: Ribavirin (RBV)<br>* Tablets containing 200 mg of ribavirin. RBV dosed according to weight-based and renal dosing tables in study protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with sustained virologic response at 12 weeks post-treatment (SVR12) | SVR12 defined as achieving 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. If a participant does not have any HCV RNA measurements in this time period then the participant will be considered as SVR12 failure, unless there are preceding and subsequent HCV RNA measurements that are both LLOQ (either TD or TND). | Week 16 (12 weeks post treatment) | 
| Proportion 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 SAE or Expedited AE (EAE) reporting requirement. DAIDS AE Grading Table (V2.1) and DAIDS EAE Manual (V2.0) are used. | From study treatment initiation to 4 weeks after study treatment discontinuation (Week 8) | 
| Number of participants who complete 4 weeks of treatment without discontinuation due to AEs | Number of participants who complete 4 weeks of treatment without discontinuation due to AEs | From study entry to Week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants with HCV RNA less than LLOQ | Proportion of participants with HCV RNA less than LLOQ (TD or TND) | Weeks 1, 2, 4, 8, 12, 28 | 
| Number of participants with HCV virologic failure | Virologic failure defined as failure to achieve unquantifiable HCV RNA and confirmed increase in HCV RNA greater than 1 log10 from on-treatment nadir | Weeks 1, 2, 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Hepatitis C Infection, Glecaprevir, Pibrentasvir, 4 weeks, Direct-acting antivirals