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

NCT ID: NCT03069365

Last Updated: 2019-03-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 101 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-28
• Study Completion Date: 2018-06-05

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.

Conditions

Hepatitis C Virus (HCV)

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

Glecaprevir/pibrentasvir

Intervention Type: DRUG

Film-coated tablet

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

Group Type: EXPERIMENTAL

Glecaprevir/pibrentasvir

Intervention Type: DRUG

Film-coated tablet

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

Group Type: EXPERIMENTAL

Glecaprevir/pibrentasvir

Intervention Type: DRUG

Film-coated tablet

Interventions

Glecaprevir/pibrentasvir

Film-coated tablet

Intervention Type: DRUG

Other Intervention Names

ABT-493/ABT-530; MAVYRET

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AbbVie

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

AbbVie Inc.

Role: STUDY_DIRECTOR

AbbVie

Locations

Scripps Clinic /ID# 159116

La Jolla, California, United States

Huntington Medical Foundation /ID# 160653

Pasadena, California, United States

Tampa General Medical Group /ID# 159115

Tampa, Florida, United States

Northwest Louisiana Nephrology /ID# 160652

Shreveport, Louisiana, United States

Massachusetts General Hospital /ID# 159114

Boston, Massachusetts, 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

Carolinas Medical Center /ID# 159113

Charlotte, North Carolina, United States

University of Pennsylvania /ID# 159117

Philadelphia, Pennsylvania, United States

Thomas Jefferson University /ID# 159754

Philadelphia, Pennsylvania, United States

TX Liver Inst, Americ Res Corp /ID# 159111

San Antonio, Texas, United States

Zeidler Ledcor Centre /ID# 160600

Edmonton, Alberta, Canada

Vancouver ID Research and Care /ID# 160598

Vancouver, British Columbia, Canada

GIRI Gastrointestinal Research Institute /ID# 160599

Vancouver, British Columbia, Canada

Toronto General Hospital /ID# 160601

Toronto, Ontario, Canada

Universitatsklinikum Mannheim /ID# 160829

Mannheim, Baden-Wurttemberg, Germany

Universitätsklinikum Frankfurt /ID# 160826

Frankfurt am Main, Hesse, Germany

Med Hochschule Hanover /ID# 160827

Hanover, , Germany

Univ Johannes Gutenberg /ID# 160828

Mainz, , Germany

General Hospital of Athens Laiko /ID# 160725

Athens, Attica, Greece

Gen Univ Hosp Alexandroupolis /ID# 160724

Alexandroupoli, , Greece

General Hospital of Athens Evaggelismos and Ophthalmiatrio of Athens Polyclinic /ID# 160726

Athens, , Greece

Bioclinic Thessaloniki /ID# 160723

Thessaloniki, , Greece

A.O.U. Policlinico S.Orsola-Malpighi /ID# 163349

Bologna, Emilia-Romagna, Italy

Policlinico A. Gemelli /ID# 160719

Rome, Lazio, Italy

Policlinico Paolo Giaccone /Id# 160718

Palermo, Sicily, Italy

A.O. Uni Giovanni e Ruggi /ID# 160720

Salerno, , Italy

HepID - Diagnostyka I Terapia /ID# 161083

Lublin, Lublin Voivodeship, Poland

Uniwersytecki Szpital Kliniczn /ID# 161081

Bialystok, , Poland

VA Caribbean Healthcare System /ID# 160754

San Juan, , Puerto Rico

School of Medicine University of Puerto Rico-Medical Sciences Campus /ID# 160755

San Juan, , Puerto Rico

Hanyang University Seoul Hospi /ID# 160259

Seongdong, Seoul Teugbyeolsi, South Korea

Severance Hospital /ID# 160261

Seoul, Seoul Teugbyeolsi, South Korea

Asan Medical Center /ID# 160260

Seoul, , South Korea

Hospital Regional de Malaga /ID# 159976

Málaga, Malaga, Spain

Hospital Parc de Salut del Mar /ID# 159975

Barcelona, , Spain

Hospital Universitario Doce de /ID# 159974

Madrid, , Spain

Karolinska Uni /ID# 159523

Stockholm, , Sweden

Countries

United States; Canada; Germany; Greece; Italy; Poland; Puerto Rico; South Korea; Spain; Sweden

References

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.

Reference Type: DERIVED

PMID: 35174470 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31821716 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2016-004182-60

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

M16-127

Identifier Type: -

Identifier Source: org_study_id