A Study to Assess Resistance and Durability of Response to ABT-493 and/or ABT-530
- Registration Number
- NCT02441283
- Lead Sponsor
- AbbVie
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 384
- Participant is male or female 18 years of age or older
- 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
- 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.
- 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.
- Participant completed the post-treatment period of an eligible prior study.
- 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).
- Receipt of any investigational HCV antiviral treatment after receiving ABT-493 and/or ABT-530 in the prior study.
- Participants who experienced non-virologic treatment failure due to premature discontinuation of study drug in prior study of ABT-493/ABT-530.
- Participation in AbbVie's Study M15-942 protocol for re-treatment for virologic failure in the prior Phase 2 or 3 study.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description HCV-infected Participants ABT-493 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. HCV-infected Participants ABT-530 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.
- Primary Outcome Measures
Name Time Method 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 From the end of treatment in the previous study up to 3 years post-treatment 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).
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 From the end of treatment in the previous study up to 3 years post-treatment 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.
Number of Participants With Persistence of Resistance-Associated Amino Acid Variants Among Those Experiencing Virologic Failure From Day 1 to Month 12 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.
- Secondary Outcome Measures
Name Time Method Mean Concentration of Interferon Gamma-induced Protein 10 (IP-10) Over Time From Day 1 up to 3 years post-treatment 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.
Number of Participants With Medical Events Related to Progression of Liver Disease or Hepatitis C Virus Infection After Day 1 up to 3 years post-treatment 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.
Mean FibroTest Score Over Time From Day 1 up to 3 years post-treatment 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.
Mean Aspartate Transaminase to Platelet Ratio Index (APRI) Over Time From Day 1 up to 3 years post-treatment 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.
Mean FibroScan Scores Over Time Up to 3 years post-treatment 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.
Trial Locations
- Locations (42)
Toronto Liver Centre /ID# 155401
🇨🇦Toronto, Ontario, Canada
Digestive Health Specialists of the Southeast /ID# 136725
🇺🇸Dothan, Alabama, United States
Southern California Res. Ctr. /ID# 141799
🇺🇸Coronado, California, United States
eStudySite San Diego /ID# 141040
🇺🇸San Diego, California, United States
Midway Immunology and Research /ID# 169477
🇺🇸Fort Pierce, Florida, United States
Carolinas Center for Liver Dis /ID# 155390
🇺🇸Statesville, North Carolina, United States
TX Clinical Research Institute /ID# 141037
🇺🇸Arlington, Texas, United States
St. Vincent's Hospital, Darlinghurst /ID# 155395
🇦🇺Darlinghurst, New South Wales, Australia
St. Vincents Hospital /ID# 155394
🇦🇺East Lismore, New South Wales, Australia
Royal Brisbane and Women's Hospital /ID# 155396
🇦🇺Herston, Queensland, Australia
Westmead Hospital /ID# 155392
🇦🇺Westmead, New South Wales, Australia
Royal Adelaide Hospital /ID# 155391
🇦🇺Adelaide, South Australia, Australia
UZ Leuven /ID# 155398
🇧🇪Leuven, Belgium
University of Calgary /ID# 155400
🇨🇦Calgary, Alberta, Canada
Auckland City Hospital /ID# 155403
🇳🇿Auckland, New Zealand
Gastro-Hepato & Geriatric Ctr /ID# 141060
🇵🇷Ponce, Puerto Rico
King's College Hospital NHS /ID# 155406
🇬🇧London, United Kingdom
The Royal London Hospital /ID# 155405
🇬🇧London, London, City Of, United Kingdom
Derriford Hospital /ID# 155407
🇬🇧Plymouth, United Kingdom
Felizarta /ID# 141033
🇺🇸Bakersfield, California, United States
Binghamton Gastroenterology /ID# 141026
🇺🇸Binghamton, New York, United States
Inquest Clinical Research /ID# 141045
🇺🇸Baytown, Texas, United States
Bon Secours St. Mary's Hospita /ID# 165106
🇺🇸Richmond, Virginia, United States
Gastroenterologisch-Hepatologi /ID# 169820
🇩🇪Kiel, Germany
Research & Education, Inc. /ID# 169591
🇺🇸San Diego, California, United States
eStudySite San Diego /ID# 141047
🇺🇸San Diego, California, United States
eStudySite San Diego /ID# 141048
🇺🇸San Diego, California, United States
Henry Ford Health System /ID# 141039
🇺🇸Detroit, Michigan, United States
Quality Medical Research, PLLC /ID# 141042
🇺🇸Nashville, Tennessee, United States
TX Liver Inst, Americ Res Corp /ID# 136727
🇺🇸San Antonio, Texas, United States
St. Mary's Hospital /ID# 155404
🇬🇧London, United Kingdom
CHU St. Pierre /ID# 155399
🇧🇪Brussels, Belgium
Louisiana Research Ctr. LLC /ID# 141024
🇺🇸Shreveport, Louisiana, United States
Northwest Gastroenterology Cli /ID# 141036
🇺🇸Portland, Oregon, United States
Delta Research Partners /ID# 141028
🇺🇸Bastrop, Louisiana, United States
Innovative Care P.S.C. /ID# 141061
🇵🇷San Juan, Puerto Rico
Cliniques Universitaires Saint Luc /ID# 155397
🇧🇪Woluwe-Saint-Lambert, Bruxelles-Capitale, Belgium
Universitätsklinikum Frankfurt /ID# 169817
🇩🇪Frankfurt am Main, Hessen, Germany
Mauss, Schmutz, Hegener, Athma /ID# 155402
🇩🇪Dusseldorf, Germany
Klinical Investigations Group /ID# 141059
🇵🇷San Juan, Puerto Rico
Royal Melbourne Hospital /ID# 155393
🇦🇺Parkville, Victoria, Australia
Gastro One /ID# 169478
🇺🇸Germantown, Tennessee, United States