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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infection; Hepatitis C Infection
• Intervention / Treatment: Drug: Glecaprevir/Pibrentasvir (G/P)

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2

Contacts and Locations

Study Locations

• Brazil
  • Rio de Janeiro, Brazil, 21045
    • Instituto de Pesquisa Clinica Evandro Chagas (12101)
• United States
  • California
    • San Diego, California, United States, 92103
      • Ucsd, Avrc Crs (701)
    • San Francisco, California, United States, 94110
      • University of California, San Francisco HIV/AIDS CRS (801)
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital CRS (6101)
  • District of Columbia
    • Washington, District of Columbia, United States, 20005
      • Whitman-Walker Institute, Inc. CRS (31791)
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Adult AIDS CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital ACTG CRS (101)
  • New York
    • New York, New York, United States, 10032
      • Columbia Physicians and Surgeons CRS (30329)
    • New York, New York, United States, 10010
      • Weill Cornell Chelsea CRS (7804)
    • New York, New York, United States, 10065
      • Weill Cornell Upton CRS (7803)
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • Unc Aids Crs (3201)
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington AIDS CRS (1401)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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.; Other Names: Mavyret

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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.	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	From study entry to Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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	From Week 1 to Week 16

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	At Step 2 entry (median time of Step 2 entry was at 21 weeks after study entry.

Collaborators and Investigators

• Sponsor: Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); AbbVie
• Investigators: Study Chair: Arthur Y. Kim, MD, Massachusetts General Hospital (MGH) CRS; Study Chair: Susanna Naggie, MD, MHS, Duke University Medical Center CRS; Study Chair: David Wyles, MD, University of Colorado Hospital CRS

Study record dates

Study Major Dates

• Study Start (Actual): November 20, 2019
• Primary Completion (Actual): May 18, 2023
• Study Completion (Actual): August 22, 2023

Study Registration Dates

• First Submitted: July 31, 2019
• First Submitted That Met QC Criteria: July 31, 2019
• First Posted (Actual): August 2, 2019

Study Record Updates

• Last Update Posted (Actual): July 11, 2024
• Last Update Submitted That Met QC Criteria: July 2, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Acute Hepatitis C Infection; Glecaprevir; Pibrentasvir; 4 weeks; Direct-acting antivirals
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Infections; Communicable Diseases; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin
• Other Study ID Numbers: ACTG A5380; UM1AI068636 (U.S. NIH Grant/Contract); 38553 (Registry Identifier: DAIDS-ES Registry Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie results in the publication, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months following publication and throughout period of funding of the ACTG Network by NIH.

IPD Sharing Access Criteria

• With whom?

  • Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group.

• For what types of analyses?

  • To achieve aims in the proposal approved by the AIDS Clinical Trials Group.

• By what mechanism will data be made available?

  • Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/about-actg/templates-and-forms. Researchers of approved proposals will need to sign an ACTG Data Use Agreement before receiving the data.

• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes