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

Hepatitis C Virus (HCV) Clinical Trial

— EXPEDITION-5  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03069365
• Other study ID #: M16-127
• Secondary ID: 2016-004182-60
• Status: Completed
• Phase: Phase 3
• Start date: March 28, 2017
• Est. completion date: June 5, 2018

Study information

• Verified date: January 2019
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 101
• Est. completion date: June 5, 2018
• Est. primary completion date: February 20, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus (HCV)
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Glecaprevir/pibrentasvir
Film-coated tablet

Locations

Country	Name	City	State
Canada	Zeidler Ledcor Centre /ID# 160600	Edmonton	Alberta
Canada	Toronto General Hospital /ID# 160601	Toronto	Ontario
Canada	GIRI Gastrointestinal Research Institute /ID# 160599	Vancouver	British Columbia
Canada	Vancouver ID Research and Care /ID# 160598	Vancouver	British Columbia
Germany	Universitätsklinikum Frankfurt /ID# 160826	Frankfurt am Main	Hessen
Germany	Med Hochschule Hanover /ID# 160827	Hannover
Germany	Univ Johannes Gutenberg /ID# 160828	Mainz
Germany	Universitatsklinikum Mannheim /ID# 160829	Mannheim	Baden-Wuerttemberg
Greece	Gen Univ Hosp Alexandroupolis /ID# 160724	Alexandroupolis
Greece	General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 160726	Athens
Greece	General Hospital of Athens Laiko /ID# 160725	Athens	Attiki
Greece	Bioclinic Thessaloniki /ID# 160723	Thessaloniki
Italy	A.O.U. Policlinico S.Orsola-Malpighi /ID# 163349	Bologna	Emilia-Romagna
Italy	Policlinico Paolo Giaccone /Id# 160718	Palermo	Sicilia
Italy	Policlinico A. Gemelli /ID# 160719	Roma	Lazio
Italy	A.O. Uni Giovanni e Ruggi /ID# 160720	Salerno
Korea, Republic of	Hanyang University Seoul Hospi /ID# 160259	Seongdong	Seoul Teugbyeolsi
Korea, Republic of	Asan Medical Center /ID# 160260	Seoul
Korea, Republic of	Severance Hospital /ID# 160261	Seoul	Seoul Teugbyeolsi
Poland	Uniwersytecki Szpital Kliniczn /ID# 161081	Bialystok
Poland	HepID - Diagnostyka I Terapia /ID# 161083	Lublin	Lubelskie
Puerto Rico	School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 160755	San Juan
Puerto Rico	VA Caribbean Healthcare System /ID# 160754	San Juan
Spain	Hospital Parc de Salut del Mar /ID# 159975	Barcelona
Spain	Hospital Universitario Doce de /ID# 159974	Madrid
Spain	Hospital Regional de Malaga /ID# 159976	Málaga	Malaga
Sweden	Karolinska Uni /ID# 159523	Stockholm
United States	Massachusetts General Hospital /ID# 159114	Boston	Massachusetts
United States	Carolinas Medical Center /ID# 159113	Charlotte	North Carolina
United States	Scripps Clinic /ID# 159116	La Jolla	California
United States	North Shore University Hospital /ID# 159108	New Hyde Park	New York
United States	Columbia Univ Medical Center /ID# 159112	New York	New York
United States	Huntington Medical Foundation /ID# 160653	Pasadena	California
United States	Thomas Jefferson University /ID# 159754	Philadelphia	Pennsylvania
United States	University of Pennsylvania /ID# 159117	Philadelphia	Pennsylvania
United States	TX Liver Inst, Americ Res Corp /ID# 159111	San Antonio	Texas
United States	Northwest Louisiana Nephrology /ID# 160652	Shreveport	Louisiana
United States	Tampa General Medical Group /ID# 159115	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Canada,  Germany,  Greece,  Italy,  Korea, Republic of,  Poland,  Puerto Rico,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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