Efficacy and Safety of 8-weeks of Glecaprevir/Pibrentasvir in Treatment-Naïve Adults With HCV Genotype 1-6 and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤1

A Single Arm, Open Label, Multicenter Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment Naïve Adults With Chronic Hepatitis C Virus (HCV) Genotypes 1 - 6 Infection and Aspartate Aminotransferase to Platelet Ratio Index (APRI) ≤ 1

A study to evaluate the efficacy and safety of glecaprevir(GLE)/pibrentasvir(PIB) in treatment-naïve participants with chronic hepatitis C virus (HCV) genotypes 1-6 infection and with an aspartate aminotransferase to platelet ratio index (APRI) of less than or equal to 1.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus (HCV)
• Intervention / Treatment: Drug: Glecaprevir/Pibrentasvir

• Study Type: Interventional
• Enrollment (Actual): 230
• Phase: Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• Bulgaria
  • Varna, Bulgaria, 9000
    • DCC Mladost M /ID# 161339
  • Sofia
    • София, Sofia, Bulgaria, 1431
      • DCC Aleksandrovska /ID# 161340
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3M 1M4
      • South Health Campus /ID# 161385
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • The Moncton Hospital /ID# 161384
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • Brampton Civic Hospital /ID# 161380
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre /ID# 161381
• France
  • Bouches-du-Rhone
    • Marseille CEDEX 08, Bouches-du-Rhone, France, 13285
      • Hopital Saint Joseph /ID# 161571
  • Bretagne
    • Rennes, Bretagne, France, 35000
      • CHU de Rennes - PONTCHAILLOU /ID# 161492
  • Doubs
    • Besancon, Doubs, France, 25000
      • CHU de Besancon - Jean Minjoz /ID# 161485
  • Lorraine
    • Vandoeuvre les Nancy, Lorraine, France, 54500
      • Hopitaux de Brabois Adultes /ID# 161482
• Germany
  • Berlin, Germany, 10117
    • Charité Universitätsmedizin Campus Mitte /ID# 161395
  • Hamburg, Germany, 20146
    • ICH Study Center GmbH & Co KG /ID# 161394
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Universitätsklinikum Frankfurt /ID# 161397
  • Rheinland-Pfalz
    • Mainz, Rheinland-Pfalz, Germany, 55131
      • Universitaetsmedizin der Johannes-Gutenberg Universität Mainz /ID# 161396
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczn /ID# 162216
  • Myslowice, Poland, 41-406
    • ID Clinic /ID# 162217
  • Dolnoslaskie
    • Wrocław, Dolnoslaskie, Poland, 50-349
      • Centrum Badan Klinicznych /Id# 162218
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-884
      • HepID - Diagnostyka I Terapia /ID# 162219
• Puerto Rico
  • San Juan, Puerto Rico, 00959
    • Innovative Care P.S.C. /ID# 162787
• Russian Federation
  • Chelyabinsk, Russian Federation, 454052
    • South Ural State Medical univ /ID# 163163
  • Moscow, Russian Federation, 127473
    • A.I. Evdokimov Moscow State Un /ID# 163162
  • Tatarstan, Respublika
    • Kazan, Tatarstan, Respublika, Russian Federation, 420140
      • A. F. Agafonov Republican Clin /ID# 163164
• Spain
  • Alcorcon, Spain, 28922
    • Hospital Fundacion Alcorcon /ID# 161436
  • Barcelona, Spain, 08036
    • Hospital Clinic de Barcelona /ID# 161437
  • Barcelona, Spain, 8035
    • Hospital Vall d'Hebron /ID# 162022
  • Malaga, Spain, 29010
    • Hosp Uni Virgen de la Victoria /ID# 164383
  • Pontevedra, Spain, 36071
    • Complexo Hospitalario universi /ID# 165603
• United Kingdom
  • Bradford, United Kingdom, BD9 6RJ
    • Bradford Teaching Hospitals /ID# 161424
  • Glasgow, United Kingdom, G4 0SF
    • Glasgow Royal Infirmary /ID# 161458
  • Gloucester, United Kingdom, GL1 3NN
    • Gloucester Royal Hospital /ID# 161423
  • Newcastle Upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital /ID# 161459
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35215
      • Parkway Medical Center /ID# 161261
  • Arkansas
    • North Little Rock, Arkansas, United States, 72117
      • Arkansas Gastroenterology /ID# 161266
  • California
    • Sacramento, California, United States, 95817
      • UC Davis Medical Center /ID# 161138
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University /ID# 161258
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • Univ Maryland School Medicine /ID# 161157
    • Baltimore, Maryland, United States, 21229
      • Digestive Disease Associates - Baltimore /ID# 161260
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5008
      • University of Michigan Hospitals /ID# 161265
  • Oregon
    • Portland, Oregon, United States, 97210
      • Northwest Gastroenterology Cli /ID# 161257
  • Texas
    • Houston, Texas, United States, 77030-2783
      • Liver Associates of Texas, P.A /ID# 161262
  • Vermont
    • Burlington, Vermont, United States, 05401-1473
      • University of Vermont Medical Center /ID# 161263
  • Virginia
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Sp /ID# 161259

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Hepatitis C virus (HCV) genotype (GT) 1, 2, 3, 4, 5, or 6 infection. Mixed GT and indeterminate GT may be acceptable.
• Aspartate aminotransferase (AST) to platelet ratio index (APRI) score of less than or equal to 1, at time of screening.

• Does not have current active hepatitis B virus infection defined as:

  • positive hepatitis B surface antigen (HBsAg), OR
  • hepatitis B virus (HBV) deoxyribonucleic acid (DNA) > lower limit of quantification (LLOQ) in subjects with isolated positive anti-hepatitis B core (HBc) (i.e., negative HBsAg and anti-hepatitis B surface[HBs])
• Platelets ≥ 150,000 cells/mm³
• Albumin ≥ lower limit of normal (LLN)
• Positive anti-HCV antibody (Ab) AND plasma HCV ribonucleic acid (RNA) viral load ≥ 1,000 IU/mL at Screening and for at least 6 months before Screening.
• No past history/evidence of cirrhosis.
• No history of hepatocellular carcinoma.
• Hepatitis C virus treatment-naïve (had not received a single dose of any approved or investigational anti-HCV medication).
• If female, the subject must not be pregnant, breastfeeding, or considering becoming pregnant during the study and for 30 days after the last dose of study drug.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Glecaprevir/Pibrentasvir; Participants received oral glecaprevir/pibrentasvir (300 mg/120 mg) once daily with food for 8 weeks.	Drug: Glecaprevir/Pibrentasvir; Glecaprevir/pibrentasvir 100 mg/40 mg co-formulated tablets taken orally as 3 tablets once a day.; Other Names: ABT-493/ABT-530; MAVYRET™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in the Modified Intention-to-Treat Population With Sustained Virologic Response 12 Weeks Post-treatment (SVR12)	SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ; 15 IU/mL) 12 weeks after the last dose of study drug. The 95% confidence interval (95%CI) was calculated using the Wilson's score method. Efficacy was to be established if the lower bound of the 95%CI was greater than the threshold of 92.4%, based on the historical rate observed in glecaprevir/pibrentasvir registrational studies in treatment-naïve, non-cirrhotic patients (98.4%) minus a margin of 6%.	12 weeks after the last actual dose of study drug, Week 20

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants in the Intention-to-Treat Population With SVR12	SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the LLOQ (15 IU/mL) 12 weeks after the last dose of study drug. The 95% confidence interval was calculated using the normal approximation to the binomial distribution. Efficacy was to be established if the lower bound of the 95%CI was greater than the threshold of 91.4%, based on the mITT threshold minus an expected 1% rate of non-virological SVR failures.	12 weeks after the last actual dose of study drug, Week 20
Percentage of Participants With On-treatment Virologic Failure	On-treatment virologic failure was defined as one of the following conditions: confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < 15 IU/mL during the Treatment Period; or; confirmed increase from nadir in HCV RNA (two consecutive HCV RNA measurements > 1 log₁₀ IU/mL above nadir) at any time point during the Treatment Period; or; HCV RNA ≥ 15 IU/mL at end of treatment with at least 6 weeks of treatment, where the HCV RNA value must be collected on or after Study Drug Day 36 and study drug duration ≥ 36 days.	Up to 8 weeks
Percentage of Participants With Post-treatment Relapse	Post-treatment relapse was defined as confirmed HCV RNA ≥ LLOQ between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment with HCV RNA levels < LLOQ at the end of treatment.	From the end of treatment (Week 8) through 12 weeks after the last dose of study drug (Week 20)

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Fontana RJ, Lens S, McPherson S, Elkhashab M, Ankoma-Sey V, Bondin M, Dos Santos AGP, Xue Z, Trinh R, Porcalla A, Zeuzem S. Efficacy and Safety of 8 Weeks of Glecaprevir/Pibrentasvir in Treatment-Naive, HCV-Infected Patients with APRI </= 1 in a Single-Arm, Open-Label, Multicenter Study. Adv Ther. 2019 Dec;36(12):3458-3470. doi: 10.1007/s12325-019-01123-0. Epub 2019 Oct 23.

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 7, 2017
• Primary Completion (ACTUAL): August 13, 2018
• Study Completion (ACTUAL): August 13, 2018

Study Registration Dates

• First Submitted: July 7, 2017
• First Submitted That Met QC Criteria: July 7, 2017
• First Posted (ACTUAL): July 11, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 4, 2019
• Last Update Submitted That Met QC Criteria: August 12, 2019
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: platelet; chronic hepatitis C virus (HCV); glecaprevir; pibrentasvir; Hepatitis; HCV genotype; aspartate aminotransferase; Aspartate aminotransferase to Platelet Ratio Index (APRI); Sustained Virologic Response 12 weeks post dosing (SVR12)
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C
• Other Study ID Numbers: M16-133; 2016-004876-23 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols and clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.
• IPD Sharing Time Frame: Data requests can be submitted at any time and the data will be accessible for 12 months, with possible extensions considered.
• IPD Sharing Access Criteria: Access to this clinical trial data can be requested by any qualified researchers who engage in rigorous, independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a Data Sharing Agreement (DSA). For more information on the process, or to submit a request, visit the following link.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No