A Study to Assess Resistance and Durability of Response to ABT-493 and/or ABT-530

A Follow-up Study to Assess Resistance and Durability of Response to AbbVie Direct-Acting Antiviral Agent (DAA) Therapy (ABT-493 and/or ABT-530) in Subjects Who Participated in Phase 2 or 3 Clinical Studies for the Treatment of Chronic Hepatitis C Virus (HCV) Infection

This was a long-term follow-up study to evaluate the durability of sustained virologic response (SVR), persistence of direct-acting antiviral agent (DAA) resistance, and clinical outcomes for participants who received glecaprevir (ABT-493) and/or pibrentasvir (ABT-530) in prior AbbVie Phase 2 or 3 clinical studies for the treatment of chronic hepatitis C virus (HCV) infection.

Study Overview

• Status: Completed
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: ABT-493; Drug: ABT-530

Detailed Description

This was a Phase 2/3, multicenter study offered to participants who received at least one dose of an ABT-493- and/or ABT-530-containing regimen at any dose level in an eligible prior AbbVie Phase 2 or 3 study for the treatment of chronic HCV and elected to enroll in this study. The participant must have completed the follow-up period of the prior eligible AbbVie study. Participants were followed for a total of approximately 3 years after their last dose of DAA in the previous HCV clinical study. The 3 years were inclusive of any post-treatment period in the prior study, as well as any gaps between the end of the prior study and enrollment in this study.

• Study Type: Interventional
• Enrollment (Actual): 384
• Phase: Phase 2; Phase 3

Expanded Access

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Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St. Vincent's Hospital, Darlinghurst /ID# 155395
    • East Lismore, New South Wales, Australia, 2480
      • St. Vincents Hospital /ID# 155394
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital /ID# 155392
  • Queensland
    • Herston, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital /ID# 155396
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital /ID# 155391
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • Royal Melbourne Hospital /ID# 155393
• Belgium
  • Brussels, Belgium, 1000
    • CHU St. Pierre /ID# 155399
  • Leuven, Belgium, 3000
    • UZ Leuven /ID# 155398
  • Bruxelles-Capitale
    • Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium, 1200
      • Cliniques Universitaires Saint Luc /ID# 155397
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary /ID# 155400
  • Ontario
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre /ID# 155401
• Germany
  • Dusseldorf, Germany, 40237
    • Mauss, Schmutz, Hegener, Athma /ID# 155402
  • Kiel, Germany, 24146
    • Gastroenterologisch-Hepatologi /ID# 169820
  • Hessen
    • Frankfurt am Main, Hessen, Germany, 60590
      • Universitätsklinikum Frankfurt /ID# 169817
• New Zealand
  • Auckland, New Zealand, 1023
    • Auckland City Hospital /ID# 155403
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Gastro-Hepato & Geriatric Ctr /ID# 141060
  • San Juan, Puerto Rico, 00909
    • Klinical Investigations Group /ID# 141059
  • San Juan, Puerto Rico, 00959
    • Innovative Care P.S.C. /ID# 141061
• United Kingdom
  • London, United Kingdom, SE5 9RS
    • King's College Hospital NHS /ID# 155406
  • London, United Kingdom, W2 1NY
    • St. Mary's Hospital /ID# 155404
  • Plymouth, United Kingdom, PL6 8DH
    • Derriford Hospital /ID# 155407
  • London, City Of
    • London, London, City Of, United Kingdom, E1 1BB
      • The Royal London Hospital /ID# 155405
• United States
  • Alabama
    • Dothan, Alabama, United States, 36305
      • Digestive Health Specialists of the Southeast /ID# 136725
  • California
    • Bakersfield, California, United States, 93301
      • Felizarta /ID# 141033
    • Coronado, California, United States, 92118-1408
      • Southern California Res. Ctr. /ID# 141799
    • San Diego, California, United States, 92105
      • Research & Education, Inc. /ID# 169591
    • San Diego, California, United States, 92120
      • eStudySite San Diego /ID# 141040
    • San Diego, California, United States, 92120
      • eStudySite San Diego /ID# 141047
    • San Diego, California, United States, 92120
      • eStudySite San Diego /ID# 141048
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research /ID# 169477
  • Louisiana
    • Bastrop, Louisiana, United States, 71220
      • Delta Research Partners /ID# 141028
    • Shreveport, Louisiana, United States, 71105-6800
      • Louisiana Research Ctr. LLC /ID# 141024
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System /ID# 141039
  • New York
    • Binghamton, New York, United States, 13903
      • Binghamton Gastroenterology /ID# 141026
  • North Carolina
    • Statesville, North Carolina, United States, 28677-3471
      • Carolinas Center for Liver Dis /ID# 155390
  • Oregon
    • Portland, Oregon, United States, 97210
      • Northwest Gastroenterology Cli /ID# 141036
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One /ID# 169478
    • Nashville, Tennessee, United States, 37211
      • Quality Medical Research, PLLC /ID# 141042
  • Texas
    • Arlington, Texas, United States, 76012
      • TX Clinical Research Institute /ID# 141037
    • Baytown, Texas, United States, 77521-2415
      • Inquest Clinical Research /ID# 141045
    • San Antonio, Texas, United States, 78215
      • TX Liver Inst, Americ Res Corp /ID# 136727
  • Virginia
    • Richmond, Virginia, United States, 23226
      • Bon Secours St. Mary's Hospita /ID# 165106

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant is male or female 18 years of age or older
2. Participant has received at least one dose of an ABT-493- and/or ABT- 530 containing regimen in a prior AbbVie hepatitis C virus (HCV) Phase 2 or 3 study
3. The interval between the last dose of the AbbVie direct-acting antiviral agent (DAA) therapy from the previous clinical study and enrollment in Study M13-576 must be no longer than 2 years for subjects who have not been retreated. Participants who have been treated with a commercially available anti-HCV treatment may be enrolled greater than 2 years after the last dose of the AbbVie DAA therapy from the previous clinical study.
4. Participant must voluntarily sign and date the informed consent form approved by an Independent Review Board or Ethics Committee prior to the initiation of any study-specific procedures.
5. Participant completed the post-treatment period of an eligible prior study.

Exclusion Criteria:

1. The investigator considers the participant unsuitable for the study for any reasons (e.g., failure to comply with study procedures in the prior AbbVie clinical study).
2. Receipt of any investigational HCV antiviral treatment after receiving ABT-493 and/or ABT-530 in the prior study.
3. Participants who experienced non-virologic treatment failure due to premature discontinuation of study drug in prior study of ABT-493/ABT-530.
4. Participation in AbbVie's Study M15-942 protocol for re-treatment for virologic failure in the prior Phase 2 or 3 study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: HCV-infected Participants; Hepatitis C virus (HCV)-infected participants who received ABT-493 and/or ABT-530 in prior Phase 2 or 3 clinical studies with these agents for the treatment of chronic HCV and were not retreated prior to entering this study. No AbbVie study drug was administered in this study.	Drug: ABT-493; ABT-493 was not administered in this study. This study was a follow-up for participants who received the drug in prior studies.; Other Names: Glecaprevir; Drug: ABT-530; ABT-530 was not administered in this study. This study was a follow-up for participants who received the drug in prior studies.; Other Names: Pibrentasvir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Maintained a Sustained Virologic Response (SVR) Out of Those Who Achieved SVR12 in a Prior Study With an ABT-493- and/or ABT-530-containing Regimen	Maintaining a sustained virologic response (SVR) is defined as having Hepatitis C virus ribonucleic acid (HCV RNA) value consistently below the lower limit of quantification (< LLOQ) from the end of treatment in the previous study throughout Study M13-576 (this study).	From the end of treatment in the previous study up to 3 years post-treatment
Percentage of Participants Who Relapsed or Had a New Hepatitis C Virus (HCV) Infection at Any Time up to the Last Follow-up in This Study Among Participants Who Achieved SVR12 in a Prior Study With an ABT-493- and/or ABT-530-containing Regimen	Relapse was defined as confirmed Hepatitis C virus ribonucleic acid (HCV RNA) greater than or equal to the lower limit of quantification (≥ LLOQ) between end of treatment and up to and including the last HCV RNA measurement collected in this study for a participant with HCV RNA < LLOQ at Final Treatment Visit who completed treatment, excluding reinfection. HCV reinfection was defined as confirmed HCV RNA ≥ LLOQ after the end of treatment in a participant who had HCV RNA < LLOQ at Final Treatment Visit, along with the post-treatment detection of a different HCV genotype, subtype, or clade compared with baseline, as determined by phylogenetic analysis of the NS3 or NS5A, and/or NS5B gene sequences.	From the end of treatment in the previous study up to 3 years post-treatment
Number of Participants With Persistence of Resistance-Associated Amino Acid Variants Among Those Experiencing Virologic Failure	Plasma samples for HCV resistance testing were collected at study visits. The variants in nonstructural viral protein 3 (NS3) and nonstructural viral protein 5A (NS5A) at amino acid positions of interest were analyzed by next generation sequencing relative to baseline and prototypic reference sequences.	From Day 1 to Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection	Any events (i.e., diagnoses) related to liver disease progression and/or HCV infection considered to be clinically significant by the investigator that began or worsened after Day 1 were documented until the end of the study or initiation of re-treatment for HCV (if applicable). Significant events related to liver disease progression include the development of cirrhosis, events indicative of hepatic decompensation, (including: variceal bleeding, new ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, hepato-renal syndrome, hepatic hydrothorax or other evidence of hepatic decompensation considered to be significant by the investigator), change in the Child-Pugh category (e.g., change from Child-Pugh Class A to Child-Pugh Class B), the occurrence of hepatocellular carcinoma, liver transplantation and/or death.	After Day 1 up to 3 years post-treatment
Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time	A plasma sample for IP-10 testing was collected at study visits for all participants, until the end of the study or initiation of re-treatment for HCV (if applicable). IP-10 is used to assess liver fibrosis in participants with chronic liver disease.	From Day 1 up to 3 years post-treatment
Mean FibroTest Score Over Time	A serum sample for FibroTest evaluation was collected at study visits for all participants, until the end of the study or initiation of re-treatment for HCV (if applicable). FibroTest uses six biomarkers to generate a score that correlates to the degree of liver damage in participants. Scores range from 0 to 1, with higher scores indicating more severe liver fibrosis.	From Day 1 up to 3 years post-treatment
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time	A serum sample for aspartate transaminase evaluation and platelets were collected at study visits for all participants, until the end of the study or initiation of re-treatment for HCV (if applicable). The aspartate transaminase to platelet ratio index (APRI) is used to assess liver fibrosis in participants with chronic liver disease. Scores range from 0 to ≥ 2.0, with scores < 0.5 predictive of no liver fibrosis; scores >1.5 significant fibrosis; and scores > 2.0 indicative of cirrhosis.	From Day 1 up to 3 years post-treatment
Mean FibroScan Scores Over Time	The FibroScan test is used to assess liver fibrosis in participants with chronic liver disease. This was not performed as a study procedure, but any available results from source documents were summarized. For participants with Hepatitis C infection, a Fibroscan score of 2-7 kPa indicates no liver scarring or mild scarring; a score of 8 or 9 is associated with moderate liver scarring; 9-14 indicates severe liver scarring; and 14 or higher is indicative of advanced liver scarring, cirrhosis.	Up to 3 years post-treatment

Collaborators and Investigators

• Sponsor: AbbVie

Publications and helpful links

General Publications

• Poordad F, Felizarta F, Yao BB, Overcash JS, Hassanein T, Agarwal K, Gane E, Shaw D, Waters M, Krishnan P, Topp A, Burroughs M, Nevens F. Durability of sustained virological response to glecaprevir/pibrentasvir and resistance development: A long-term follow-up study. Liver Int. 2022 Jun;42(6):1278-1286. doi: 10.1111/liv.15211. Epub 2022 Mar 14.

Study record dates

Study Major Dates

• Study Start (Actual): June 22, 2015
• Primary Completion (Actual): October 15, 2019
• Study Completion (Actual): October 15, 2019

Study Registration Dates

• First Submitted: April 29, 2015
• First Submitted That Met QC Criteria: May 11, 2015
• First Posted (Estimate): May 12, 2015

Study Record Updates

• Last Update Posted (Actual): September 21, 2020
• Last Update Submitted That Met QC Criteria: August 31, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Keywords: Chronic hepatitis C; Hepatitis C virus; Hepatitis C; Sustained virologic response; Direct Acting Antiviral
• 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
• Other Study ID Numbers: M13-576; 2015-000452-24 (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