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

Hepatitis C Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02441283
• Other study ID #: M13-576
• Secondary ID: 2015-000452-24
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: June 22, 2015
• Est. completion date: October 15, 2019

Study information

• Verified date: August 2020
• Source: AbbVie
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 384
• Est. completion date: October 15, 2019
• Est. primary completion date: October 15, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis C

Intervention

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.
• 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.

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital /ID# 155391	Adelaide	South Australia
Australia	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	Royal Melbourne Hospital /ID# 155393	Parkville	Victoria
Australia	Westmead Hospital /ID# 155392	Westmead	New South Wales
Belgium	CHU St. Pierre /ID# 155399	Brussels
Belgium	UZ Leuven /ID# 155398	Leuven
Belgium	Cliniques Universitaires Saint Luc /ID# 155397	Woluwe-Saint-Lambert	Bruxelles-Capitale
Canada	University of Calgary /ID# 155400	Calgary	Alberta
Canada	Toronto Liver Centre /ID# 155401	Toronto	Ontario
Germany	Mauss, Schmutz, Hegener, Athma /ID# 155402	Dusseldorf
Germany	Universitätsklinikum Frankfurt /ID# 169817	Frankfurt am Main	Hessen
Germany	Gastroenterologisch-Hepatologi /ID# 169820	Kiel
New Zealand	Auckland City Hospital /ID# 155403	Auckland
Puerto Rico	Gastro-Hepato & Geriatric Ctr /ID# 141060	Ponce
Puerto Rico	Innovative Care P.S.C. /ID# 141061	San Juan
Puerto Rico	Klinical Investigations Group /ID# 141059	San Juan
United Kingdom	King's College Hospital NHS /ID# 155406	London
United Kingdom	St. Mary's Hospital /ID# 155404	London
United Kingdom	The Royal London Hospital /ID# 155405	London	London, City Of
United Kingdom	Derriford Hospital /ID# 155407	Plymouth
United States	TX Clinical Research Institute /ID# 141037	Arlington	Texas
United States	Felizarta /ID# 141033	Bakersfield	California
United States	Delta Research Partners /ID# 141028	Bastrop	Louisiana
United States	Inquest Clinical Research /ID# 141045	Baytown	Texas
United States	Binghamton Gastroenterology /ID# 141026	Binghamton	New York
United States	Southern California Res. Ctr. /ID# 141799	Coronado	California
United States	Henry Ford Health System /ID# 141039	Detroit	Michigan
United States	Digestive Health Specialists of the Southeast /ID# 136725	Dothan	Alabama
United States	Midway Immunology and Research /ID# 169477	Fort Pierce	Florida
United States	Gastro One /ID# 169478	Germantown	Tennessee
United States	Quality Medical Research, PLLC /ID# 141042	Nashville	Tennessee
United States	Northwest Gastroenterology Cli /ID# 141036	Portland	Oregon
United States	Bon Secours St. Mary's Hospita /ID# 165106	Richmond	Virginia
United States	TX Liver Inst, Americ Res Corp /ID# 136727	San Antonio	Texas
United States	eStudySite San Diego /ID# 141040	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	Research & Education, Inc. /ID# 169591	San Diego	California
United States	Louisiana Research Ctr. LLC /ID# 141024	Shreveport	Louisiana
United States	Carolinas Center for Liver Dis /ID# 155390	Statesville	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AbbVie

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Germany,  New Zealand,  Puerto Rico,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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