A Study to Evaluate the Efficacy and Safety of Glecaprevir/Pibrentasvir in Adults With Chronic Hepatitis C Virus Genotype 1 - 6 Infection and Renal Impairment (EXPEDITION-5)

A Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Glecaprevir/Pibrentasvir in Renally-Impaired Adults With Chronic Hepatitis C Virus Genotype 1 - 6 Infection (EXPEDITION-5)

This was a Phase 3b, open-label, non-randomized, multicenter study to evaluate the efficacy and safety of glecaprevir/pibrentasvir (GLE/PIB) in participants with chronic hepatitis C virus (HCV) genotype (GT) 1 - 6 infection without liver cirrhosis or with compensated liver cirrhosis and with chronic renal impairment in participants who were either HCV treatment-naïve (TN) or prior treatment-experienced (TE) with interferon (IFN) or pegylated interferon (PegIFN) with or without ribavirin (RBV), or sofosbuvir (SOF) plus RBV with or without pegIFN.

Study Overview

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

Detailed Description

The study included a 42-day screening period, a treatment period of either 8, 12, or 16 weeks, and a 24-week post-treatment period. The duration of treatment was determined by product labeling. Participants received glecaprevir/pibrentasvir (GLE/PIB) 300 mg/120 mg once daily. Participants who completed or prematurely discontinued the treatment period were followed for 24 weeks after their last dose of study drug to monitor safety, hepatitis C virus ribonucleic acid (HCV RNA), and the emergence and persistence of viral substitutions.

• Study Type: Interventional
• Enrollment (Actual): 101
• Phase: Phase 3

Expanded Access

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

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2X8
      • Zeidler Ledcor Centre /ID# 160600
  • British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2C7
      • Vancouver ID Research and Care /ID# 160598
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • GIRI Gastrointestinal Research Institute /ID# 160599
  • Ontario
    • Toronto, Ontario, Canada, M5G 2C4
      • Toronto General Hospital /ID# 160601
• Germany
  • Hannover, Germany, 30625
    • Med Hochschule Hanover /ID# 160827
  • Mainz, Germany, 55131
    • Univ Johannes Gutenberg /ID# 160828
  • Baden-Wuerttemberg
    • Mannheim, Baden-Wuerttemberg, Germany, 68167
      • Universitatsklinikum Mannheim /ID# 160829
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Universitätsklinikum Frankfurt /ID# 160826
• Greece
  • Alexandroupolis, Greece, 68100
    • Gen Univ Hosp Alexandroupolis /ID# 160724
  • Athens, Greece, 10676
    • General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 160726
  • Thessaloniki, Greece, 54622
    • Bioclinic Thessaloniki /ID# 160723
  • Attiki
    • Athens, Attiki, Greece, 115 27
      • General Hospital of Athens Laiko /ID# 160725
• Italy
  • Salerno, Italy, 84100
    • A.O. Uni Giovanni e Ruggi /ID# 160720
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • A.O.U. Policlinico S.Orsola-Malpighi /ID# 163349
  • Lazio
    • Roma, Lazio, Italy, 00168
      • Policlinico A. Gemelli /ID# 160719
  • Sicilia
    • Palermo, Sicilia, Italy, 90127
      • Policlinico Paolo Giaccone /Id# 160718
• Korea, Republic of
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center /ID# 160260
  • Seoul Teugbyeolsi
    • Seongdong, Seoul Teugbyeolsi, Korea, Republic of, 04763
      • Hanyang University Seoul Hospi /ID# 160259
    • Seoul, Seoul Teugbyeolsi, Korea, Republic of, 03722
      • Severance Hospital /ID# 160261
• Poland
  • Bialystok, Poland, 15-276
    • Uniwersytecki Szpital Kliniczn /ID# 161081
  • Lubelskie
    • Lublin, Lubelskie, Poland, 20-884
      • HepID - Diagnostyka I Terapia /ID# 161083
• Puerto Rico
  • San Juan, Puerto Rico, 00921-3201
    • VA Caribbean Healthcare System /ID# 160754
  • San Juan, Puerto Rico, 00935
    • School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 160755
• Spain
  • Barcelona, Spain, 08003
    • Hospital Parc de Salut del Mar /ID# 159975
  • Madrid, Spain, 28041
    • Hospital Universitario Doce de /ID# 159974
  • Malaga
    • Málaga, Malaga, Spain, 29009
      • Hospital Regional de Malaga /ID# 159976
• Sweden
  • Stockholm, Sweden, SE-141 86
    • Karolinska Uni /ID# 159523
• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic /ID# 159116
    • Pasadena, California, United States, 91105
      • Huntington Medical Foundation /ID# 160653
  • Florida
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group /ID# 159115
  • Louisiana
    • Shreveport, Louisiana, United States, 71101
      • Northwest Louisiana Nephrology /ID# 160652
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital /ID# 159114
  • New York
    • New Hyde Park, New York, United States, 11040
      • North Shore University Hospital /ID# 159108
    • New York, New York, United States, 10032-3725
      • Columbia Univ Medical Center /ID# 159112
  • North Carolina
    • Charlotte, North Carolina, United States, 28203
      • Carolinas Medical Center /ID# 159113
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104-5502
      • University of Pennsylvania /ID# 159117
    • Philadelphia, Pennsylvania, United States, 19107-4414
      • Thomas Jefferson University /ID# 159754
  • Texas
    • San Antonio, Texas, United States, 78215
      • TX Liver Inst, Americ Res Corp /ID# 159111

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:

• Male or female (of non-childbearing potential or using allowed contraceptive methods) at least 18 years of age time of Screening
• Participant had a positive anti-hepatitis C virus (HCV) antibody (Ab) and plasma HCV ribonucleic acid (RNA) greater than or equal to 1000 IU/mL at the Screening Visit.
• Participant had an estimated glomerular filtration rate (eGFR) less than 45 mL/min/1.73 m^2 as estimated by the Modification of Diet in Renal Disease (MDRD) method at Screening according to the following formula: eGFR (mL/min/1.73 m^2 ) = 175 × (Serum Creatinine) ^-1.154 × Age^-0.203 × (0.742 if female) × (1.212 if black), or were dialysis dependent. Subjects requiring dialysis had to have been receiving dialysis for at least 1 month prior to enrollment, and may have been on hemodialysis or peritoneal dialysis.
• Cirrhotic participants only: absence of hepatocellular carcinoma (HCC) as indicated by a negative ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months prior to Screening or a negative ultrasound at Screening. Participants who had an ultrasound with results suspicious of HCC followed by a subsequent negative CT or MRI of the liver were eligible for the study.

Exclusion Criteria:

• Female participants who were pregnant, breastfeeding, or were considering becoming pregnant during the study or for approximately 30 days after the last dose of study drug
• Current hepatitis B virus (HBV) or human immunodeficiency virus (HIV) infection on screening tests, defined as:
• Positive test result at Screening for hepatitis B surface antigen (HBsAg), or;
• HBV deoxyribonucleic acid (DNA) greater than lower limit of quantification (LLOQ) in participants with isolated positive hepatitis B core antibody (HBcAb), (i.e., negative HBsAg and Anti-HBsAg), or;
• Positive anti-HIV antibody (Ab).
• Any current or historical clinical evidence of decompensated cirrhosis, including any current or past evidence of Child-Pugh B or C classification, hepatic encephalopathy or variceal bleeding; radiographic evidence of small ascites; or prior or current empiric use of lactulose/rifaximin for neurologic indications. Prophylactic use of beta blockers was not exclusionary.
• Clinical history of acute renal failure in the 3 months prior to Screening
• History of severe, life-threatening, or other significant sensitivity to any excipients of the study drugs
• Clinically significant abnormalities or co-morbidities, or recent (within 6 months prior to study drug administration) alcohol or drug abuse that could preclude adherence to the protocol in the opinion of the investigator
• Receipt of any investigational or commercially available direct acting anti-HCV agents other than sofosbuvir

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GLE/PIB for 8 weeks; HCV genotype 1,2,4-6 non-cirrhotic, treatment-naive or treatment-experienced; genotype 3 non-cirrhotic, treatment-naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB): three 100 mg/40 mg co-formulated tablets once daily with food for 8 weeks	Drug: Glecaprevir/pibrentasvir; Film-coated tablet; Other Names: MAVYRET; ABT-493/ABT-530
Experimental: GLE/PIB for 12 weeks; HCV genotype 1,2,4-6 compensated cirrhosis, treatment-naive or treatment-experienced; genotype 3 compensated cirrhosis, treatment- naïve participants treated with glecaprevir/pibrentasvir (GLE/PIB): three 100 mg/40 mg co-formulated tablets once daily with food for 12 weeks	Drug: Glecaprevir/pibrentasvir; Film-coated tablet; Other Names: MAVYRET; ABT-493/ABT-530
Experimental: GLE/PIB for 16 weeks; HCV genotype 3 non-cirrhotic or with compensated cirrhosis, treatment-experienced participants treated with glecaprevir/pibrentasvir (GLE/PIB): three 100 mg/40 mg co-formulated tablets once daily with food for 16 weeks	Drug: Glecaprevir/pibrentasvir; Film-coated tablet; Other Names: MAVYRET; ABT-493/ABT-530

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Dosing (SVR12)	SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) level less than the lower limit of quantification (LLOQ) 12 weeks after the last actual dose of study drug.	12 weeks after the last actual dose of study drug

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With On-treatment Virologic Failure	On-treatment virologic failure was defined as: Confirmed increase from nadir in hepatitis C virus ribonucleic acid (HCV RNA) defined as confirmed increase of > 1 log (subscript)10(subscript) IU/mL above nadir during treatment; or; Confirmed HCV RNA greater than or equal to 100 IU/mL after HCV RNA less than the lower limit of quantification (LLOQ) during study drug treatment; or; HCV RNA ≥ LLOQ at the end of treatment with at least 6 weeks of treatment	Up to 16 weeks
Percentage of Participants With Post-treatment Relapse	Post-treatment relapse was defined as confirmed hepatitis C virus ribonucleic acid (HCV RNA) ≥ the lower limit of quantification (LLOQ) between the end of treatment and 12 weeks after the last dose of study drug among participants who completed treatment as planned with HCV RNA < LLOQ at the end of treatment and had post-treatment HCV RNA data; participants who had been shown to be reinfected were not considered to have relapsed. .	Up to 12 weeks after the last dose of study drug

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Brown RS Jr, Collins MA, Strasser SI, Emmett A, Topp AS, Burroughs M, Ferreira R, Feld JJ. Efficacy and Safety of 8- or 12 Weeks of Glecaprevir/Pibrentasvir in Patients with Evidence of Portal Hypertension. Infect Dis Ther. 2022 Apr;11(2):913-924. doi: 10.1007/s40121-022-00599-8. Epub 2022 Feb 17.
• Lawitz E, Flisiak R, Abunimeh M, Sise ME, Park JY, Kaskas M, Bruchfeld A, Worns MA, Aglitti A, Zamor PJ, Xue Z, Schnell G, Jalundhwala YJ, Porcalla A, Mensa FJ, Persico M. Efficacy and safety of glecaprevir/pibrentasvir in renally impaired patients with chronic HCV infection. Liver Int. 2020 May;40(5):1032-1041. doi: 10.1111/liv.14320. Epub 2019 Dec 26.

Study record dates

Study Major Dates

• Study Start (Actual): March 28, 2017
• Primary Completion (Actual): February 20, 2018
• Study Completion (Actual): June 5, 2018

Study Registration Dates

• First Submitted: February 28, 2017
• First Submitted That Met QC Criteria: February 28, 2017
• First Posted (Actual): March 3, 2017

Study Record Updates

• Last Update Posted (Actual): March 4, 2019
• Last Update Submitted That Met QC Criteria: February 6, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Chronic Kidney Disease; Compensated cirrhosis; Non-cirrhotic; Treatment naïve; Sofosbuvir (SOF); Ribavirin (RBV); Glecaprevir; Pibrentasvir; Chronic Hepatitis C Virus; Hepatitis C Virus Genotype; Interferon (IFN); Pegylated interferon (pegIFN)
• 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; Hepatitis, Chronic; Hepatitis C, Chronic
• Other Study ID Numbers: M16-127; 2016-004182-60 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

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