To Evaluate Safety and Efficacy of FB-1603 in Hepatocellular Carcinoma Patient Receiving Transarterial Chemoembolization

A Phase I/II Randomized, Double-blinded Study of FB-1603 to Evaluate the Safety and Efficacy in Hepatocellular Carcinoma Patients Receiving Transarterial Chemoembolization (FECHT Trial)

The goal of this clinical trial is to assess the efficacy of FB-1603 on improving liver function impairment in hepatocellular carcinoma patients receiving transarterial chemoembolization. The main question it aims to answer is:

Changes in the level of liver function parameters, including AST, ALT, or total bilirubin, from baseline to Visit 3, Visit 4, Visit 5, and Visit 6

There is a comparison group: Researchers will compare arm 1 placebo to see if FB-1603 is work to treat the liver function.

Participants will

1. Take drug FB-1603 990mg/day, FB-1603 1980mg/day or a placebo every day for 10 weeks.
2. Visit the clinic on day 4, 7, 10, 14, 28, 56 and 84 (follow-up)

Study Overview

• Status: Recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Placebo; Drug: FB-1603

Detailed Description

I. Objectives:

• Primary objective: To assess the efficacy of FB-1603 on improving liver function impairment after transarterial chemoembolization (TACE) in subjects

• Secondary objective:

  • To evaluate the safety of FB-1603 in subjects
  • To evaluate selected parameters indicative of clinical efficacy
  • To assess postembolization syndrome improvement of FB-1603 compared with placebo
  • To evaluate virologic test level of FB-1603 compared with placebo
  • To assess liver stiffness change of FB-1603 compared with placebo

• Exploratory objective:

  • To assess the antioxidation activity of FB-1603 in hepatocellular carcinoma (HCC) subjects after TACE

II. Investigational product:

1. Name: FB-1603 oral capsule (FB-1603)
2. Dosage form: 165 mg oral capsule

3. Dose(s): Each arm consisted of 40 subjects.

   • Arm 1: 4*Placebo each time, TID (three times a Day), two weeks before and eight weeks after TACE
   • Arm 2: 2*FB-1603 165 mg oral capsule and 2*Placebo each time, TID (990 mg/day), two weeks before and eight weeks after TACE
   • Arm 3: 4*FB-1603 165 mg oral capsule each time, TID (1980 mg/day), two weeks before and eight weeks after TACE

4. Dosing schedule:

   All enrolled subjects will be randomly assigned (1:1:1) to receive low dose (990 mg/day), high dose (1980 mg/day) of FB-1603 165 mg oral capsule or placebo capsule three times a day for 10 weeks. Each subject starts receiving FB-1603 165 mg oral capsule or placebo capsule on two weeks before and eight weeks after TACE. The investigational drugs should be taken orally about 10 minutes before the breakfast, lunch, and dinner

5. Mechanism of action:

The proposed mechanism is that FB-1603 can improve liver function via decrease of oxidative stress. In previous study conducted in diethylnitrosamine (DEN) induced liver cirrhosis and cancer rat model (Report #: FENTU30SEP2009) shown that the extent of oxidative stress determined by NBT (Nitro blue tetrazolium) staining was significant decreased in treatment group orally administrated with 0.8, 1 or 2 g/kg/day of FB-1603 compared with the control group.

III. Developmental phase: phase I and II

IV. Study design:

1. placebo control study
2. Blinding: double blind
3. Randomized: yes
4. Parallel
5. Duration of treatment: days 10 weeks months years
6. Titration: forced
7. Single center

VI. Study procedures:

This is a randomized, double-blind, 10-week dose-finding study in 3 parallel arms.

The study is conducted as follows: eligible subjects are randomized parallelly into 3 arms. Each arm comprises 40 subjects orally receive active (FB-1603 165 mg oral capsule) or placebo (placebo capsule) two weeks before and eight weeks after TACE. Each subject will begin receiving FB-1603 oral capsule or placebo two weeks before TACE. As the appearance of the placebo capsule is identical to the FB-1603 165 mg oral capsule, study blinding will be maintained during the administration procedure. Other than staff involved in randomization, the sponsor, participants, and staff involved in the preparation of the study drug are blinded. Each subject is assigned to either active (FB-1603 165 mg oral capsule) or placebo treatment using a block randomization algorithm. Three times a day (TID) doses of FB-1603 165 mg oral capsule are escalated capsule low dose (990 mg/day) and high dose (1980 mg/day).

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Tsung-Yen Ho, Master; Phone Number: 116 886-2-2627-5585; Email: rdrad001@gmail.com
• Study Contact Backup: Name: Jyun-Yuan Huang, Doctor; Phone Number: 111 886-2-2627-5585; Email: jyhuang@febico.com.tw

Study Locations

• Taiwan
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Kai-Wen Huang, MD, MS, PhD; Phone Number: 66144 886-2-2312-3456; Email: skywing@ntuh.gov.tw
    • Contact: Kai-Wen Huang, MD, MS, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Aged 18-75 years (inclusive) of either gender
2. Willing and able to provide signed informed consent
3. Confirmed diagnosis of hepatocellular carcinoma by radiology, histology, or cytology
4. Subject has the willingness to undergo TACE
5. ECOG performance Status of 0-1
6. The patient is expected to survive more than 3 months

7. Laboratory values should meet all the following standards at the screening visit:

   A. AST, ALP and ALT are ≤ 5x ULN. B. International Normalized Ratio (INR) ≤ 1.5 C. Prothrombin time < 4 sec above upper limit of normal D. Absolute neutrophil count ≥ 1.5×10^9/L; Hemoglobin ≥ 9 g/dL; platelet ≥ 50×10^9/L.

   E. Total bilirubin < 2.5 mg/dL F. Serum creatinine < 2 mg/dL

8. With liver stiffness measurement >7 kPa (assessed by FibroScan®) or > 1.5 m/sec (assessed by acoustic radiation force impulse elastography (ARFI))

Exclusion Criteria:

1. Patients with evidence of macrovascular invasion
2. Patients with evidence of extrahepatic spread
3. Any condition representing a contraindication to TACE as determined by the investigators
4. Acute liver failure or liver function decompensation patient perform, such as hepatic encephalopathy, and ascites
5. Patients with acute or chronic active hepatitis B or C infection and are recommended to receive HBV or HCV treatment, e.g., Patient with HBV DNA ≥ 20,000 IU/ml or with detectable HCV RNA
6. Patients who have severe organic diseases on heart, lungs, brain, kidney, and gastrointestinal tract by the judgment of investigators
7. Patients with chronic pancreatitis
8. Patients who are taking any prohibited drugs that might interfere the trial
9. Patients who are not able to express the chief complaint, for example, the patients with psychosis and severe neurosis
10. Patients with active infections (infection requiring the use systemic antibiotics) within 4 weeks prior to the screening visit

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo; 4*Placebo oral capsule each time, TID (three times a Day). treatment period: start two weeks before TACE until eight weeks after TACE.	Drug: Placebo; Placebo oral capsule
Experimental: low dose FB-1603 (990mg/day); 2*FB-1603 165 mg oral capsule and 2*Placebo oral capsule each time, TID (990 mg/day). treatment period: start two weeks before TACE until eight weeks after TACE.	Drug: Placebo; Placebo oral capsule; Drug: FB-1603; FB-1603 (165 mg/cap) oral capsule
Experimental: high dose FB-1603 (1980mg/day); 4*FB-1603 165 mg oral capsule each time, TID (1980 mg/day). treatment period: start two weeks before TACE until eight weeks after TACE.	Drug: FB-1603; FB-1603 (165 mg/cap) oral capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the level of liver function	Changes in the level of liver function parameters, including aspartate transferase (AST), alanine transferase (ALT), or total bilirubin,	from baseline (day 0) to Visit 3 (day 4), Visit 4(day 7), Visit 5(day 10), and Visit 6(day 14)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the level of liver function	Changes in the level of liver function parameters, including AST, ALT, or total bilirubin after TACE	from baseline (day 0) to Visit 7 (day 28) and Visit 8 (day 56)
Frequency and severity of adverse event (AE) during the study	Assessment of frequency and severity of adverse event (AE) during the study	up to 84 days
Clinically significant changes in blood chemistry	Clinically significant changes in blood chemistry at each applicable visit	from baseline (day 0) to Visit 3 (day 4), Visit 4 (day 7), Visit 5 (day 10), Visit 6 (day 14), Visit 7 (day 28), Visit 8 (day 56) and follow-up visit (day 84)
Clinically significant changes in coagulation test	Clinically significant changes in coagulation test at each applicable visit including international normalized ratio (INR) and prothrombin time.	from baseline (day 0) to Visit 3 (day 4), Visit 4 (day 7), Visit 5 (day 10), Visit 6 (day 14), Visit 7 (day 28), Visit 8 (day 56) and follow-up visit (day 84)
Changes in measurements of indocyanine green retention (ICG)	Changes in measurements of indocyanine green retention (ICG) test at each applicable visit	from baseline (day 0) to Visit 3 (day 4) and Visit 5 (day 10)
Level of liver fibrosis	Level of liver fibrosis by elastography and fibrosis-4 (FIB-4) index	at the screening visit (day -28 to -15), Visit 8 (day 56) and FV/ET (day 84)
Incidence of postembolization syndrome	Incidence of postembolization syndrome	from baseline (day 0) to Visit 3 (day 4), Visit 4 (day 7), Visit 5 (day 10), Visit 6 (day 14), Visit 7 (day 28) and Visit 8 (day 56)
Length of hospital stay after TACE	Length of hospital stay after TACE	Visit 2 (day 0)
Changes in the level of quantitative HBsAg or HCV RNA	Changes in the level of quantitative HBsAg or HCV RNA measured by PCR	from screening visit (day -28 to -15) to Visit 8 (day 56) and FV/ET (day 84)

Collaborators and Investigators

• Sponsor: Febico Biomedical Corp.
• Collaborators: National Taiwan University Hospital
• Investigators: Principal Investigator: Kai-Wen Huang, MD, MS, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2024
• Primary Completion (Estimated): June 7, 2027
• Study Completion (Estimated): August 6, 2027

Study Registration Dates

• First Submitted: June 17, 2024
• First Submitted That Met QC Criteria: June 24, 2024
• First Posted (Actual): June 27, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 25, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: FB-1603_TACE_PII_2022_1

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No