Direct Acting Antiviral-Post Authorization Safety Study

Study Overview
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Brief Summary
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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.

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

Conditions
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Hepatitis C, Hepatocellular Carcinoma

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Prospective<br>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<br>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?
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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 |