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

NCT04290936 | Unknown Phase 4

• 1 other identifier: IN-TW-320-5598
• Study Type: interventional
• Target: 402
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

HCC Patients After Curative Treatment With Low HBV Viral Load

Outcome Measures

Primary Outcomes (1)

• Incidence of Hepatocellular carcinoma(HCC) recurrence

  Incidence of HCC recurrence

  Up to 2 years.

Secondary Outcomes (6)

• Hepatocellular carcinoma(HCC) recurrence

  Up to 3 years.

• Hepatocellular carcinoma(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

  Up to 3 years.

• Changes in the renal function

  Up to 3 years.

• Changes in the bone density

  Up to 3 years.

Study Arms (3)

Arm 1

EXPERIMENTAL

NUC-naïve patients will be randomization into Tenofovir Alafenamide(TAF) treatment.

Drug: Vemlidy® (Tenofovir Alafenamide; TAF)

Arm 2

PLACEBO COMPARATOR

NUC-naïve patients will be randomization into placebo arm.

Drug: Placebo

Arm 3

ACTIVE COMPARATOR

NUCs-treated patients will be switched to Tenofovir Alafenamide(TAF) treatment.

Drug: Vemlidy® (Tenofovir Alafenamide; TAF)

Interventions

Vemlidy® (Tenofovir Alafenamide; TAF) DRUG

Dosage form: Oral Tablets; Dosage: 25mg; Frequency: One tablet with meals, once daily(QD).

Arm 1; Arm 3

Placebo DRUG

Dosage form: Oral Tablets; Dosage: N/A; Frequency: One tablet with meals, once daily(QD).

Arm 2

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• Taipei Veterans General Hospital, Taiwan: lead

Study Sites (4)

Kaohsiung Medical University Chung-Ho Memorial Hospital

Kaohsiung City, State..., 807, Taiwan

ACTIVE NOT RECRUITING

National Taiwan University Hospital

Taipei, State..., 100, Taiwan

RECRUITING

Tri-Service General Hospital

Taipei, State..., 114, Taiwan

ACTIVE NOT RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

MeSH Terms

Interventions

tenofovir alafenamide

Central Study Contacts

Yi-Hsiang Huang, M.D. Ph.D.

CONTACT

+886-2-28757506; yhhuang@vghtpe.gov.tw

ChiehJu Lee, Master

CONTACT

+886-939859265; ssbugi@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Yi-Hsiang Huang, M.D., Ph.D.

Model Details: Part 1: NUC-naïve patients will be randomization into tenofovir alafenamide(TAF) or placebo arm in 1:1 ratio. Part 2: NUCs-treated patients will be switched to tenofovir alafenamide(TAF) treatment.

Study Record Dates

• First Submitted: February 27, 2020
• First Posted: March 2, 2020
• Study Start: October 16, 2020
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: July 9, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

TW (4)