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 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.

Study Overview

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

Detailed Description

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.

• 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: 16 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); 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); Fixed-dose combination (FDC) tablets containing 100 mg of glecaprevir and 40 mg of pibrentasvir; administered as 3 tablets orally.; Drug: Ribavirin (RBV); Tablets containing 200 mg of ribavirin. RBV dosed according to weight-based and renal dosing tables in study protocol.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AIDS Clinical Trials Group
• 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 15, 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): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 25, 2024
• Last Verified: March 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 available throughout period of funding of the AIDS Clinical Trials Group 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 AIDS Clinical Trials Group 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