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

NCT04042740 | Completed Phase 2 Results DMC FDA Drug

• 3 other identifiers: ACTG A538038553UM1AI068636
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 12

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.

Conditions

Hepatitis C Infection; HIV Infection

Keywords

Acute Hepatitis C Infection; Glecaprevir; Pibrentasvir; 4 weeks; Direct-acting antivirals

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (2)

• Percentage of Participants With HCV RNA Less Than LLOQ

  Weeks 1, 2, 4, 8, 12, 28

• Number of Participants With HCV Virologic Failure

  From Week 1 to Week 16

Other Outcomes (1)

• Number of Participants by HCV Re-Treatment Regimen in Step 2

  At Step 2 entry (median time of Step 2 entry was at 21 weeks after study entry.

Study Arms (1)

Glecaprevir/Pibrentasvir (G/P)

EXPERIMENTAL

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)

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.

Also known as: Mavyret

Glecaprevir/Pibrentasvir (G/P)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Acute HCV infection (or reinfection) within 24 weeks prior to entry
• Detectable HCV RNA at the screening visit

You may not qualify if:

• 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

Sponsors & Collaborators

• Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections: lead
• AbbVie: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (12)

Ucsd, Avrc Crs (701)

San Diego, California, 92103, United States

Location

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

San Francisco, California, 94110, United States

Location

University of Colorado Hospital CRS (6101)

Aurora, Colorado, 80045, United States

Location

Whitman-Walker Institute, Inc. CRS (31791)

Washington D.C., District of Columbia, 20005, United States

Location

Johns Hopkins Adult AIDS CRS

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital ACTG CRS (101)

Boston, Massachusetts, 02114, United States

Location

Weill Cornell Chelsea CRS (7804)

New York, New York, 10010, United States

Location

Columbia Physicians and Surgeons CRS (30329)

New York, New York, 10032, United States

Location

Weill Cornell Upton CRS (7803)

New York, New York, 10065, United States

Location

Unc Aids Crs (3201)

Chapel Hill, North Carolina, 27514, United States

Location

University of Washington AIDS CRS (1401)

Seattle, Washington, 98104, United States

Location

Instituto de Pesquisa Clinica Evandro Chagas (12101)

Rio de Janeiro, 21045, Brazil

Location

Related Publications (1)

• Kim AY, Kang M, Umbleja T, Nunes EP, Marks KM, Luetkemeyer AF, Koebele C, Wimbish C, Fierer DS, Kliemann DA, Solomon SS, Kort J, Kiser JJ, Lauer GM, Chung RT, Sowah LA, Alston-Smith BL, Wyles DL, Naggie S; A5380 Study Team. Short Course Therapy With Glecaprevir/Pibrentasvir for Early Hepatitis C Virus Infection: PURGE-C. Clin Infect Dis. 2025 Jul 30:ciaf305. doi: 10.1093/cid/ciaf305. Online ahead of print.

  PMID: 40736252 DERIVED

Related Links

• Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (DAIDS AE Grading Table), corrected Version 2.1, July 2017
• Manual for Expedited Reporting of Adverse Events to DAIDS (DAIDS EAE Manual), Version 2.0, January 2010

MeSH Terms

Conditions

Hepatitis C; HIV Infections

Interventions

glecaprevir and pibrentasvir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases; Digestive System Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, a DLH Holdings Company

ACTGCT.gov@fstrf.org

(301) 628-3348

Study Officials

• 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 CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2019
• First Posted: August 2, 2019
• Study Start: November 20, 2019
• Primary Completion: May 18, 2023
• Study Completion: August 22, 2023
• Last Updated: July 11, 2024
• Results First Posted: July 11, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and throughout period of funding of the ACTG Network by NIH.
• 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.

Locations

BR (1); US (11)