Clinical trial NCT03069365: 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
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Hepatitis C Virus (HCV)
Keywords: Chronic Hepatitis C Virus
Chronic Kidney Disease
Glecaprevir
Pibrentasvir
Hepatitis C Virus Genotype
Compensated cirrhosis
Non-cirrhotic
Interferon (IFN)
Treatment naïve
Sofosbuvir (SOF)
Pegylated interferon (pegIFN)
Ribavirin (RBV)
Lead sponsor: AbbVie
Sponsor class: INDUSTRY
First posted: 2017-03-03
Enrollment: 101
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants Achieving Sustained Virologic Response 12 Weeks Post Dosing (SVR12)
timeFrame: 12 weeks after the last actual dose of study drug
Secondary outcomes:
measure: Percentage of Participants With On-treatment Virologic Failure
timeFrame: Up to 16 weeks
measure: Percentage of Participants With Post-treatment Relapse
timeFrame: Up to 12 weeks after the last dose of study drug
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Clinic /ID# 159116
state: California
city: Pasadena
country: United States
facility: Huntington Medical Foundation /ID# 160653
state: California
city: Tampa
country: United States
facility: Tampa General Medical Group /ID# 159115
state: Florida
city: Shreveport
country: United States
facility: Northwest Louisiana Nephrology /ID# 160652
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital /ID# 159114
state: Massachusetts
city: New Hyde Park
country: United States
facility: North Shore University Hospital /ID# 159108
state: New York
city: New York
country: United States
facility: Columbia Univ Medical Center /ID# 159112
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center /ID# 159113
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania /ID# 159117
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University /ID# 159754
state: Pennsylvania
city: San Antonio
country: United States
facility: TX Liver Inst, Americ Res Corp /ID# 159111
state: Texas
city: Edmonton
country: Canada
facility: Zeidler Ledcor Centre /ID# 160600
state: Alberta
city: Vancouver
country: Canada
facility: Vancouver ID Research and Care /ID# 160598
state: British Columbia
city: Vancouver
country: Canada
facility: GIRI Gastrointestinal Research Institute /ID# 160599
state: British Columbia
city: Toronto
country: Canada
facility: Toronto General Hospital /ID# 160601
state: Ontario
city: Mannheim
country: Germany
facility: Universitatsklinikum Mannheim /ID# 160829
state: Baden-Wuerttemberg
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt /ID# 160826
state: Hessen
city: Hannover
country: Germany
facility: Med Hochschule Hanover /ID# 160827
city: Mainz
country: Germany
facility: Univ Johannes Gutenberg /ID# 160828
city: Athens
country: Greece
facility: General Hospital of Athens Laiko /ID# 160725
state: Attiki
city: Alexandroupolis
country: Greece
facility: Gen Univ Hosp Alexandroupolis /ID# 160724
city: Athens
country: Greece
facility: General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 160726
city: Thessaloniki
country: Greece
facility: Bioclinic Thessaloniki /ID# 160723
city: Bologna
country: Italy
facility: A.O.U. Policlinico S.Orsola-Malpighi /ID# 163349
state: Emilia-Romagna
city: Roma
country: Italy
facility: Policlinico A. Gemelli /ID# 160719
state: Lazio
city: Palermo
country: Italy
facility: Policlinico Paolo Giaccone /Id# 160718
state: Sicilia
city: Salerno
country: Italy
facility: A.O. Uni Giovanni e Ruggi /ID# 160720
city: Seongdong
country: Korea, Republic of
facility: Hanyang University Seoul Hospi /ID# 160259
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Severance Hospital /ID# 160261
state: Seoul Teugbyeolsi
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center /ID# 160260
city: Lublin
country: Poland
facility: HepID - Diagnostyka I Terapia /ID# 161083
state: Lubelskie
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczn /ID# 161081
city: San Juan
country: Puerto Rico
facility: VA Caribbean Healthcare System /ID# 160754
city: San Juan
country: Puerto Rico
facility: School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 160755
city: Málaga
country: Spain
facility: Hospital Regional de Malaga /ID# 159976
state: Malaga
city: Barcelona
country: Spain
facility: Hospital Parc de Salut del Mar /ID# 159975
city: Madrid
country: Spain
facility: Hospital Universitario Doce de /ID# 159974
city: Stockholm
country: Sweden
facility: Karolinska Uni /ID# 159523
Study officials:
affiliation: AbbVie
name: AbbVie Inc.
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.