A Study of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment-Naive Adults With Chronic Hepatitis C Virus (HCV) Genotype 1-6 Infection and Compensated Cirrhosis (EXPEDITION-8)

A Single Arm, Open-label Study to Evaluate the Efficacy and Safety of Glecaprevir (GLE)/Pibrentasvir (PIB) in Treatment Naïve Adults With Chronic Hepatitis C Virus (HCV) Genotype 1-6 Infection and Compensated Cirrhosis

A Phase 3b, single arm, open-label, multicenter study in treatment naïve adults with chronic HCV infection and compensated cirrhosis to assess the safety of 8 weeks of treatment with glecaprevir/pibrentasvir and to demonstrate the efficacy of the sustained virologic response 12 weeks post dosing (SVR12) rates of 8 weeks of treatment with glecaprevir/pibrentasvir compared to the historical SVR12 rates of 12 weeks of treatment with glecaprevir/pibrentasvir.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 343
• Phase: Phase 3

Expanded Access

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

Contacts and Locations

Study Locations

• Bulgaria
  • Sofia, Bulgaria, 1407
    • Tokuda Hospital Sofia /ID# 163422
  • Sofia, Bulgaria, 1463
    • DCC Fokus-5 - LZIP /ID# 163338
  • Sofia, Bulgaria, 1527
    • Univ Hosp for Active Treat /ID# 163330
  • Sofia, Bulgaria, 1612
    • UMHAT Sv. Ivan Rilski /ID# 163332
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary /ID# 161185
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 3M9
      • Percuro Clinical Research, Ltd /ID# 161184
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Qe Ii Hsc /Id# 161178
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Research /ID# 161179
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital /ID# 161182
• Czechia
  • Plzen, Czechia, 301 00
    • Research Site s.r.o /ID# 163020
  • Prague, Czechia, 120 00
    • KlinMed s.r.o. /ID# 162893
  • Prague, Czechia, 140 21
    • Institut Klinicke a Experimeth /ID# 162900
• France
  • Clermont Ferrand, France, 63100
    • CHU Estaing /ID# 163058
  • Creteil, France, 94010
    • Hospital Henri Mondor /ID# 163061
  • Lyon, France, 69004
    • Hopital de la Croix Rousse /ID# 163073
  • Centre-Val De Loire
    • Orleans CEDEX 2, Centre-Val De Loire, France, 45067
      • CHR Orleans - Hopital de la Source /ID# 163072
  • Haute-Garonne
    • TOULOUSE Cedex 9, Haute-Garonne, France, 31059
      • Hôpital Purpan /ID# 163065
  • Somme
    • Amiens CEDEX 1, Somme, France, 80054
      • CHU Amiens Picardie /ID# 163071
• Greece
  • Kifissia, Greece, 14564
    • General and Oncology Hospital /ID# 162784
  • Larisa, Greece, 41110
    • Reg Gen Univ Hosp Larissa /ID# 162783
  • Thessaloniki, Greece, 54622
    • Bioclinic Thessaloniki /ID# 162785
  • Attiki
    • Athens, Attiki, Greece, 115 27
      • General Hospital of Athens Laiko /ID# 162786
• Hungary
  • Budapest, Hungary, 1111
    • Budai Hepatologiai Centrum /ID# 166511
  • Budapest, Hungary, 1125
    • Szent Janos Korhaz /ID# 166542
• Ireland
  • Dublin, Ireland, D09 XR63
    • Beaumont Hospital /ID# 162618
  • Dublin 4, Ireland
    • St Vincent's Hospital /ID# 162617
  • Dublin
    • Dublin 8, Dublin, Ireland, D08 E9P6
      • St. James's Hospital /ID# 162619
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus /ID# 162023
  • Haifa, Israel, 3436212
    • The Lady Davis Carmel MC /ID# 162017
  • Ramat Gan, Israel, 5262100
    • Sheba Medical Center /ID# 162028
  • Tel-Aviv
    • Tel Aviv-Yafo, Tel-Aviv, Israel, 6423906
      • Tel Aviv Sourasky Medical Ctr /ID# 162185
• Italy
  • Milan, Italy, 20157
    • Polo Universitario Luigi Sacco /ID# 162339
  • Campania
    • Napoli, Campania, Italy, 80131
      • Universita della Campania Luigi Vanvitelli /ID# 162337
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • A.O.U. Policlinico S.Orsola-Malpighi /ID# 162335
  • Lombardia
    • Milano, Lombardia, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda /ID# 162340
  • Milano
    • Rozzano, Milano, Italy, 20089
      • Istituto Clinico Humanitas /ID# 162336
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczn /ID# 162757
  • Myslowice, Poland, 41-406
    • ID Clinic /ID# 162759
  • Dolnoslaskie
    • Wrocław, Dolnoslaskie, Poland, 50-349
      • Centrum Badan Klinicznych, Przychodnia Badan Klinicznych /ID# 162760
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-884
      • HepID - Diagnostyka I Terapia /ID# 162761
• Portugal
  • Lisboa, Portugal, 1649-035
    • Centro Hospitalar Lisboa Norte, EPE /ID# 163785
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto EPE /ID# 163765
  • Porto, Portugal, 4200-319
    • Centro Hospitalar de Sao Joao /ID# 163766
  • Lisboa
    • Lisbon, Lisboa, Portugal, 1169-050
      • Centro Hosp de Lisboa Central /ID# 163770
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • GHGCPR Research Institute /ID# 162608
  • Ponce, Puerto Rico, 00730
    • Instituto de Investigacion Cientifica del Sur /ID# 162566
  • San Juan, Puerto Rico, 00909
    • Klinical Investigations Group /ID# 162565
• Romania
  • Bucuresti, Romania, 010825
    • Institutul Nat. de Boli Infectioase /ID# 163488
  • Bucuresti
    • Sector 2, Bucuresti, Romania, 021105
      • Institutul National de Boli Infectioase Prof. Dr. Matei Bals /ID# 163484
    • Sector 2, Bucuresti, Romania, 021105
      • Institutul National de Boli Infectioase Prof. Dr. Matei Bals /ID# 164449
    • Sector 2, Bucuresti, Romania, 022328
      • Institutul Clinic Fundeni /ID# 163479
    • Sector 2, Bucuresti, Romania, 022328
      • Institutul Clinic Fundeni /ID# 163500
• Russian Federation
  • Moscow, Russian Federation, 105275
    • CBSI Central scientific and research institute of epidemiology /ID# 161996
  • Moscow, Russian Federation, 117593
    • Central Clinical Hospital of R /ID# 163434
  • Stavropol, Russian Federation, 355017
    • Stavropol State Medical Univ /ID# 161999
  • Tyumen, Russian Federation, 625026
    • RSAHI Consulting and Diagnostic Centre /ID# 161995
  • Samarskaya Oblast
    • Samara, Samarskaya Oblast, Russian Federation, 443063
      • LLC Medical Company Hepatolog /ID# 161998
• Spain
  • Barcelona, Spain, 08003
    • Hospital Parc de Salut del Mar /ID# 162198
  • Barcelona, Spain, 08035
    • Hospital Univ Vall d'Hebron /ID# 162199
  • Cordoba, Spain, 14004
    • Hospital Universitario Reina S /ID# 162200
  • Donostia, Spain, 20080
    • Hospital Donostia /ID# 162197
  • Oviedo, Spain, 33011
    • Hospital Univ Central Asturias /ID# 162195
• Taiwan
  • Kaohsiung, Taiwan, 80708
    • Kaohsiung Medical University Chung-Ho Memorial Hospital /ID# 162949
  • Taipei City, Taiwan, 11217
    • Taipei Veterans General Hosp /ID# 162776
  • Taichung
    • Taichung City, Taichung, Taiwan, 40447
      • China Medical University Hosp /ID# 162950
• United Kingdom
  • Crumpsall, United Kingdom, M8 5RB
    • North Manchester General /ID# 163945
  • Edinburgh, United Kingdom, EH4 2XU
    • Western General Hospital /ID# 162612
  • Nottinghamshire, United Kingdom, NG7 2UH
    • Queens Medical Centre /ID# 162615
  • Essex
    • Basildon, Essex, United Kingdom, SS16 5NL
      • Basildon University Hospital /ID# 162616
  • London, City Of
    • London, London, City Of, United Kingdom, NW3 2QG
      • The Royal Free Hospital /ID# 162614
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • St. Josephs Hosp and Med Ctr /ID# 162762
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Arizona /ID# 162314
  • Arkansas
    • Little Rock, Arkansas, United States, 72204
      • Liver Wellness Center /ID# 162244
  • California
    • Bakersfield, California, United States, 93301
      • Felizarta /ID# 162295
    • Long Beach, California, United States, 90822
      • VA Long Beach Healthcare System /ID# 162298
    • Los Angeles, California, United States, 90033
      • Usc /Id# 162248
    • San Diego, California, United States, 92154
      • Kaiser Permanente - San Diego (Palm Ave) /ID# 162289
    • Stanford, California, United States, 94305-2200
      • Stanford University School of Med /ID# 162209
    • West Hollywood, California, United States, 90048
      • Cedars-Sinai Medical Center - West Hollywood /ID# 162313
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami /ID# 162210
    • West Palm Beach, Florida, United States, 33407-3100
      • Triple O Research Institute /ID# 162300
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Piedmont Hospital /ID# 162646
  • Illinois
    • Chicago, Illinois, United States, 60611-2927
      • Northwestern University Feinberg School of Medicine /ID# 162208
  • Iowa
    • Des Moines, Iowa, United States, 50309
      • Unity Point Health /ID# 162247
    • Iowa City, Iowa, United States, 52242
      • The University of Iowa Hospita /ID# 162214
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville /ID# 162242
  • Louisiana
    • Shreveport, Louisiana, United States, 71105-6800
      • Louisiana Research Ctr. LLC /ID# 162567
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center /ID# 162291
  • Minnesota
    • Rochester, Minnesota, United States, 55905-0001
      • Mayo Clinic - Rochester /ID# 162251
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Advanced Research (STAR) LLC /ID# 162241
  • Nebraska
    • Omaha, Nebraska, United States, 68124
      • CHI Health Alegent Creighton /ID# 162286
    • Omaha, Nebraska, United States, 68198
      • Univ Nebraska Med Ctr /ID# 162285
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • Rnjms /Id# 162213
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center /ID# 162312
    • Bronx, New York, United States, 10468
      • James J. Peters VA Medical Center /ID# 162644
    • New York, New York, United States, 10021
      • Weill Cornell Medical College /ID# 161051
    • New York, New York, United States, 10029
      • Icahn School of Med Mt. Sinai /ID# 162294
  • North Carolina
    • Durham, North Carolina, United States, 27710-3000
      • Duke University Medical Center /ID# 162299
    • Fayetteville, North Carolina, United States, 28304
      • Cumberland Research Assoc /ID# 162212
    • Statesville, North Carolina, United States, 28677-3471
      • Carolinas Center for Liver Dis /ID# 162569
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland /ID# 162243
    • Cleveland, Ohio, United States, 44111
      • Cleveland Clinic /ID# 162570
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74127
      • Osuchs /Id# 162284
  • Pennsylvania
    • Allentown, Pennsylvania, United States, 18103
      • Lehigh Valley Health Network /ID# 162603
    • Pittsburgh, Pennsylvania, United States, 15213
      • Center for Liver Diseases, Oakland /ID# 162568
  • Tennessee
    • Nashville, Tennessee, United States, 37232-0011
      • Vanderbilt Univ Med Ctr /ID# 162211
  • Texas
    • Dallas, Texas, United States, 75246-1613
      • Texas Digestive Disease Consul /ID# 162648
    • Houston, Texas, United States, 77030-1501
      • University of Texas Health /ID# 162288
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Virginia Commonwealth Univ /ID# 162215
  • Wisconsin
    • Madison, Wisconsin, United States, 53792-0001
      • Univ of Wisconsin Hosp/Clinics /ID# 162645
• Vietnam
  • Hanoi, Vietnam, 100000
    • National Hospital of Tropical Diseases /ID# 167974
  • Ho Chi Minh, Vietnam, 700000
    • Hoa Hao Medic Co. Ltd. /ID# 168178
  • Ho Chi Minh, Vietnam, 700000
    • Tropical Diseases Hospital /ID# 168211

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:

• Screening laboratory result indicating Hepatitis C Virus (HCV) Genotype (GT) 1-6 infection.
• Positive plasma HCV antibody and HCV RNA viral load greater than or equal to 1000 IU/mL at Screening.
• Treatment-naive to any approved or investigational anti-HCV medication.
• Participant must be documented as cirrhotic, with a Child-Pugh score of less than or equal to 6.

Exclusion Criteria:

• Female participant who is pregnant, breastfeeding or is considering becoming pregnant during the study, or for approximately 30 days after the last dose of study drug.
• Any current or historical clinical evidence of decompensated cirrhosis.
• Positive test result at Screening for hepatitis B surface antigen (HBsAg), HBV deoxyribonucleic acid > lower limit of quantification (LLOQ) in subjects with isolated positive antibody to hepatitis B core antigen (anti-HBc) (i.e., negative HBsAg and anti-hepatitis B),or anti human immunodeficiency virus antibody (HIV Ab).
• HCV genotype performed by the central laboratory during screening indicating co-infection with more than one HCV genotype.
• History of suspected or confirmed hepatocellular carcinoma.

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 (GLE)/Pibrentasvir (PIB) for 8 weeks; Glecaprevir (GLE)/Pibrentasvir (PIB) 300 mg/120 mg once daily (QD) for 8 weeks.	Drug: Glecaprevir/Pibrentasvir; Tablet; Other Names: ABT-493; ABT-530

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response 12 Weeks Post-treatment (SVR12) in Hepatitis C Virus (HCV) Genotype (GT) 1,2,4,5 and 6-infected Participants in the Per Protocol (PP) Population	SVR12 was defined as plasma hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (<LLOQ; less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% confidence interval (CI) for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. Efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.	12 weeks after last dose of study drug
Percentage of Participants With SVR12 in HCV GT 1,2,4,5 and 6-infected Participants in the Intent-To-Treat (ITT) Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. Primary efficacy analyses were performed following a fixed-sequence testing procedure to control the type I error rate. The percentage of participants achieving SVR12 was summarized with a 2-sided 95% CI, calculated using the normal approximation to the binomial distribution. If the number of participants who failed to achieve SVR12 rate was less than 5, the Wilson's score method was used to calculate the CI.	12 weeks after last dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the PP Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 94% in the PP population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.	12 weeks after last dose of study drug
Percentage of Participants With SVR12 in HCV GT1-6-infected Participants in the ITT Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug. Efficacy of the 8-week treatment duration compared to the historical 12-week treatment duration was demonstrated if the lower bound of the 2-sided 95% CI for the percentage of participants with HCV GT1, GT2, GT3, GT4, GT5, or GT6 infection in the 8 week treatment duration achieving SVR12 was greater than 93% in the ITT population. These efficacy analyses were performed only if success was demonstrated for both primary efficacy analyses, following a fixed-sequence testing procedure.	12 weeks after the last dose of study drug
Percentage of Participants With On-treatment Virologic Failure in the ITT Population	On-treatment virologic failure was defined as confirmed HCV RNA ≥ 100 IU/mL after HCV RNA < LLOQ during treatment; confirmed increase of > 1 log(subscript)10(subscript) IU/mL above the lowest value post-baseline in HCV RNA during treatment; or HCV RNA ≥ LLOQ at end of treatment with at least 6 weeks of treatment.	8 weeks on treatment
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 as planned (defined as study drug duration ≥ 52 days for participants assigned to 8 weeks of treatment) and with HCV RNA levels < LLOQ at the end of treatment excluding participants who had been reinfected.	Up to 12 weeks after the last dose of study drug
Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the PP Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug.	12 weeks after the last dose of study drug
Percentage of HCV GT3-infected Participants Who Achieved SVR12 in the ITT Population	SVR12 was defined as HCV RNA level less than the LLOQ (less than 15 IU/mL) 12 weeks after the last dose of study drug.	12 weeks after the last dose of study drug

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Brown RS Jr, Buti M, Rodrigues L, Chulanov V, Chuang WL, Aguilar H, Horvath G, Zuckerman E, Carrion BR, Rodriguez-Perez F, Urbanek P, Abergel A, Cohen E, Lovell SS, Schnell G, Lin CW, Zha J, Wang S, Trinh R, Mensa FJ, Burroughs M, Felizarta F. Glecaprevir/pibrentasvir for 8 weeks in treatment-naive patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial. J Hepatol. 2020 Mar;72(3):441-449. doi: 10.1016/j.jhep.2019.10.020. Epub 2019 Nov 2.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 28, 2017
• Primary Completion (ACTUAL): July 31, 2019
• Study Completion (ACTUAL): November 8, 2019

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: March 22, 2017
• First Posted (ACTUAL): March 24, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 13, 2020
• Last Update Submitted That Met QC Criteria: June 24, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Keywords: Cirrhosis; Compensated Cirrhosis; Hepatitis C Virus (HCV); Pangenotypic; Treatment Naïve; Chronic Hepatitis C Virus (HCV); Glecaprevir; Pibrentasvir; Genotype (GT) 1-6
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Fibrosis; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis, Chronic; Liver Cirrhosis; Hepatitis C, Chronic
• Other Study ID Numbers: M16-135; 2016-004967-38 (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; 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
• product manufactured in and exported from the U.S.: No