Direct Acting Antiviral-Post Authorization Safety Study

DAA-PASS: A Post-Authorisation Safety Study of Early Recurrence of Hepatocellular Carcinoma in HCV-Infected Patients After Direct-Acting Antiviral Therapy

This is an independent optional sub-study parallel to TARGET-HCC (NCT02954094). The purpose of Direct-Acting Antiviral-Post Authorization Safety Study (DAA-PASS) is to investigate the impact of exposure to direct-acting antivirals (DAAs) on early recurrence of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-infected patients following successful HCC treatment interventions.

Study Overview

• Status: Completed
• Conditions: Hepatocellular Carcinoma; Hepatitis C

• Study Type: Observational
• Enrollment (Actual): 42

Contacts and Locations

Study Locations

• France
  • Nice, France
    • CHU de Nice - Hôpital L'Archet 2
  • Paris, France
    • Hôpitaux Universitaires Paris Centre
• Germany
  • Berlin, Germany
    • Charité - Universitätsmedizin Berlin
  • Frankfurt, Germany
    • Universitätsklinikum Frankfurt
  • Leipzig, Germany
    • Universitatsklinikum Leipzig
  • Magdeburg, Germany
    • Universitätsklinikum Magdeburg
• Italy
  • Milan, Italy
    • Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
  • Palermo, Italy
    • A.O.U.P. di Palermo
  • Rozzano, Italy
    • Humanitas Mirasole IRCCS
  • San Giovanni Rotondo, Italy
    • IRCCS "Casa Sollievo della Sofferenza"
• Spain
  • Madrid, Spain
    • Hospital Puerta de Hierro Majadahonda
  • Pamplona, Spain
    • Clinica Universidad de Navarra
  • Santander, Spain
    • Hospital Universitario Marques de Valdecilla
  • Sevilla, Spain
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain
    • Hospital Universitario Politècnic La Fe
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85006
      • Banner University Medical Center
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences
  • California
    • Los Angeles, California, United States, 90033
      • Norris Comprehensive Cancer Center
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Pasadena, California, United States, 91105
      • California Liver Research Institute
    • Sacramento, California, United States, 95817
      • University of California - Davis Clinical Trials
    • San Francisco, California, United States, 94158
      • University of California - San Francisco
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University
  • Florida
    • Clearwater, Florida, United States, 33762
      • Gastro Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Hepatology Research at CTRB
    • Jacksonville, Florida, United States, 32207
      • University of Florida - Health Gastroenerology
    • Miami, Florida, United States, 33136
      • Schiff Center for Liver Diseases
    • Tampa, Florida, United States, 33606
      • Tampa General Medical Group
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Hospital
    • Atlanta, Georgia, United States, 30309
      • Piedmont Atlanta Hospital
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Rush University Medical Center
    • Chicago, Illinois, United States, 60611
      • Northwestern University Division of Gastroenterology and Hepatology
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • University of Iowa Hospitals and Clinics
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University School of Medicine
  • Maryland
    • Baltimore, Maryland, United States, 21202
      • Mercy Medical Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Mississippi
    • Jackson, Mississippi, United States, 39216
      • Southern Therapy and Advanced Research LLC
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers-Robert Wood Johnson Medical School
  • New York
    • Manhasset, New York, United States, 11030
      • Northwell Health - Center for Liver Disease
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
    • New York, New York, United States, 10016
      • New York University Langone Health
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Carolinas HealthCare System Center for Liver Disease
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Health & Services Cancer Clinical Trials
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Medical Center
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • South Carolina
    • Charleston, South Carolina, United States, 29403
      • Medical University of South Carolina
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center - GI Research Office
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Dallas, Texas, United States, 75203
      • Clinical Research Institute@ Methodist Dallas Medical Center
    • Fort Worth, Texas, United States, 76104
      • Baylor Scott & White All Saints
    • Houston, Texas, United States, 77030
      • Research Specialists of Texas
    • Houston, Texas, United States, 77033
      • Research Specialists of Texas
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia Transplant Center
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
    • Richmond, Virginia, United States, 23226
      • Bon Secours Liver Institute of Virginia
  • Washington
    • Seattle, Washington, United States, 98104
      • Harborview Medical Center
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital & Clinics

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Non-Probability Sample

Study Population

The prospective DAA-PASS cohort will include a subset of HCV RNA positive participants in the TARGET-HCC study who meet entry criteria including hepatitis C (with no prior history of DAA therapy) and newly diagnosed Barcelona Clinic Liver Cancer (BCLC) Stage A HCC. Participants will be enrolled in the countries participating in TARGET-HCC which will include: United States (US), France, Germany, Italy, and Spain.

Description

Screening Inclusion Criteria:

• Current participant in TARGET-HCC
• Adults, age ≥18 years
• First diagnosis of HCC (mixed HCC/cholangiocarcinoma may be included). Diagnosis may be histological/cytological and/or radiological.
• BCLC Stage A
• Underwent, undergoing, or planned to undergo therapy for HCC, with exception that transplant as prior or planned treatment for HCC is excluded.
• HCV RNA positive

Screening Exclusion Criteria:

• Inability to provide informed consent
• HCC-free imaging (as defined in Section 9.1.1) after treatment of initial HCC prior to Screening (see Section 9.2.9 for imaging details)
• Prior liver transplantation
• Hepatitis B Virus (HBV) surface antigen positive (HBsAg)
• Previously treated with direct-acting antiviral agents (not DAA-naïve); Note that prior (peg)IFN and/or ribavirin therapy is allowed

Enrollment Inclusion Criteria:

• Continued participation in TARGET-HCC
• No recurrence or progression of initial HCC beyond BCLC Stage A prior to Enrollment/Baseline
• HCC-free imaging (as defined in Section 9.1.1) at Enrollment/Baseline (see Section 9.2.9 for imaging details; participants may remain in Screening until an HCC-free image is obtained)
• Remains DAA-naïve (prior therapy with (peg)IFN and/or ribavirin is allowed)

Enrollment Exclusion Criteria:

- Liver transplantation since Screening

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Prospective; The prospective DAA-PASS cohort will include a subset of HCV RNA positive participants in the TARGET-HCC study who meet entry criteria including hepatitis C (with no prior history of DAA therapy) and newly diagnosed Barcelona Clinic Liver Cancer (BCLC) Stage A HCC. Participants will be enrolled in the countries participating in TARGET-HCC which will include: United States (US), France, Germany, Italy, and Spain.
Historical; The historical cohort will be derived from the ITA.LI.CA database, which includes data on all consecutive patients with HCC who were managed within participating centers in Italy. The historical cohort will include patients from the ITA.LI.CA database who have active HCV infection who were not treated for HCV (IFN-based or DAA-based regimens) during the followup period, with initial HCC diagnosis BCLC Stage A, and subsequent successful treatment of HCC with curative therapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to HCC recurrence - Prospective Cohort	Time to HCC recurrence associated with DAA therapy relative to no DAA therapy in the prospective cohort.	up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of events of early HCC recurrence - Prospective Cohort	Number of events (early HCC recurrence) associated with DAA therapy relative to no DAA therapy in the prospective cohort.	up to 24 months
Time to HCC recurrence - Prospective Cohort relative to Historical Cohort	Time to HCC recurrence associated with DAA therapy in the prospective cohort relative to no DAA therapy in the historical cohort.	up to 24 months
Number of events of early HCC recurrence - Prospective Cohort relative to Historical Cohort	Number of events (early HCC recurrence) associated with DAA therapy in the prospective cohort relative to no DAA therapy in the historical cohort. historical cohort of HCV patients not exposed to DAA with initial HCC diagnosis and subsequent successful treatment of HCC.	up to 24 months

Collaborators and Investigators

• Sponsor: Target PharmaSolutions, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2018
• Primary Completion (Actual): June 30, 2021
• Study Completion (Actual): June 30, 2021

Study Registration Dates

• First Submitted: October 8, 2018
• First Submitted That Met QC Criteria: October 12, 2018
• First Posted (Actual): October 16, 2018

Study Record Updates

• Last Update Posted (Actual): July 6, 2021
• Last Update Submitted That Met QC Criteria: July 1, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Liver Neoplasms; Hepatitis; Carcinoma; Carcinoma, Hepatocellular; Hepatitis C
• Other Study ID Numbers: TARGET-HCC DAA-PASS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No