Tenofovir Alafenamide(TAF) Reduces the Risk of Hepatocellular Carcinoma(HCC) Recurrence

Decreasing Risk of Recurrence by TAF in HCC Patients After Curative Treatment With Low HBV Viral Load

Hepatocellular carcinoma(HCC) is prevalent in the hepatitis B virus(HBV) infection endemic areas. For early stage of HCC, surgical resection, radiofrequency ablation (RFA) or microwave ablation (MWA) are the main treatment options. However, the risk of recurrence is as high as 50% in 5 years by surgical resection or 60-70% in 5 years by RFA. In average, the recurrence rate of HCC at 2 years is 30%. Many factors are associated with the HCC recurrence, including HBV viral load, cirrhotic stage, tumor size, tumor number, vascular invasion, alpha-fetoprotein(AFP) level and so on. Of them, high HBV viral load is associated with the risk of HCC recurrence after surgical resection, especially on late recurrence. In one previous randomized controlled trial, patients who received lamivudine, adefovir dipivoxil, or entecavir had significantly decreased early recurrence of HCC, however, whether nucleos(t)ide analogues(NUCs) can further reduce the risk of recurrence in patients with low viral loads (<2000 IU/ml) is still unclear.

In EASL 2017 guideline, all patients with compensated or decompensated cirrhosis need antiviral treatment, with any detectable HBV DNA level and regardless of alanine aminotransferase(ALT) levels. In Taiwan, even in chronic hepatitis B(CHB) infection patients with HCC, NUC is not reimbursed if their HBV viral load was less than 2000 IU/ml. It is an important unmet medical need to understanding the role of TAF in reducing the risk of recurrence in HBV-HCC patients with low HBV viral load (HBV DNA<2000 IU/ml) and significant liver fibrosis after curative treatment (The definition of significant liver fibrosis was based on reference. In our recent retrospective study, the risk of recurrence and survival are comparable between patients with and without NUCs treatment before HCC development only if NUCs treatment can be provided after curative treatment of HCC. However, a higher risk of recurrence was observed in cirrhotic patients with prior NUCs treatment before HCC occurrence. It would be interesting to investigate the incidence of recurrence by switching to tenofovir alafenamide(TAF) after curative treatment of HCC in patients already on NUCs treatment.

Study Overview

• Status: Recruiting
• Conditions: HCC Patients After Curative Treatment With Low HBV Viral Load
• Intervention / Treatment: Drug: Vemlidy® (Tenofovir Alafenamide; TAF); Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 402
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: ChiehJu Lee, Master; Phone Number: +886-939859265; Email: ssbugi@gmail.com

Study Locations

• Taiwan
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
    • Contact: Yi-Hsaing Huang, M.D. Ph.D.; Phone Number: +886-2-28757506; Email: yhhuang@vghtpe.gov.tw
    • Principal Investigator: Yi-Hsiang Huang, M.D. Ph.D.
  • State...
    • Kaohsiung, State..., Taiwan, 807
      • Active, not recruiting
      • Kaohsiung Medical University Chung-Ho Memorial Hospital
    • Taipei, State..., Taiwan, 100
      • Recruiting
      • National Taiwan University Hospital
      • Principal Investigator: Chun-Jen Liu, M.D. Ph.D.
    • Taipei, State..., Taiwan, 114
      • Active, not recruiting
      • Tri-Service General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HBsAg-positive for more than 6 months.
• HCC after curative treatment (eight by surgical resection or RFA or MWA) with significant liver fibrosis (either by Ishak≧2, Metavir≧2, Knodell≧3) or cirrhosis and HBV DNA<2,000 IU/ml.
• The duration of curative treatment of HCC to study enrollment should be less than 90 days.
• Curative treatment is confirmed by contrast-enhanced CT or MR after the surgery/RFA/MWA.

Exclusion Criteria:

• Child-Pugh class B8-C.
• Active EV bleeding within 4 weeks.
• History of hepatic encephalopathy or intractable ascites.
• BCLC C or D.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; NUC-naïve patients will be randomization into Tenofovir Alafenamide(TAF) treatment.	Drug: Vemlidy® (Tenofovir Alafenamide; TAF); Dosage form: Oral Tablets; Dosage: 25mg; Frequency: One tablet with meals, once daily(QD).
Placebo Comparator: Arm 2; NUC-naïve patients will be randomization into placebo arm.	Drug: Placebo; Dosage form: Oral Tablets; Dosage: N/A; Frequency: One tablet with meals, once daily(QD).
Active Comparator: Arm 3; NUCs-treated patients will be switched to Tenofovir Alafenamide(TAF) treatment.	Drug: Vemlidy® (Tenofovir Alafenamide; TAF); Dosage form: Oral Tablets; Dosage: 25mg; Frequency: One tablet with meals, once daily(QD).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Hepatocellular carcinoma(HCC) recurrence	Incidence of HCC recurrence	Up to 2 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hepatocellular carcinoma(HCC) recurrence	HCC recurrence	Up to 3 years.
Hepatocellular carcinoma(HCC) recurrence in NUCs-treated patients after switched to TAF treatment	HCC recurrence in NUCs-treated patients after switched to TAF treatment	Up to 2 years.
Dynamic (kinetics) changes in the bio-markers related to hepatitis B virus(HBV) infection	HBV DNA, HBsAg, HBV RNA, HBcrAg, etc.	Up to 3 years.
Changes in the renal function	eGFR	Up to 3 years.
Changes in the bone density	Dual-energy X-ray absorptiometry(DEXA) scan	Up to 3 years.
Regression of liver fibrosis	Fibroscan	Up to 3 years.

Collaborators and Investigators

• Sponsor: Taipei Veterans General Hospital, Taiwan

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2020
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: February 27, 2020
• First Submitted That Met QC Criteria: February 27, 2020
• First Posted (Actual): March 2, 2020

Study Record Updates

• Last Update Posted (Actual): July 9, 2021
• Last Update Submitted That Met QC Criteria: July 5, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Recurrence; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: IN-TW-320-5598

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