A Randomized, Double-Blind Trial of Antroquinonol in Patients With Chronic Hepatitis B

A Randomized, Double-Blind, Dosing-Ranging, Placebo-controlled Trial of Antroquinonol in Patients With Chronic Hepatitis B

Hepatitis B virus infection is a worldwide disease and is still the most common cause of hepatocellular carcinoma (HCC).Existing treatments for hepatitis B infection have various side-effects including renal toxicity and drug resistance or failure.

Study Overview

• Status: Completed
• Conditions: HBV
• Intervention / Treatment: Drug: Antroquinonol; Other: placebo

Detailed Description

Hepatitis B virus infection is a worldwide disease and is still the most common cause of hepatocellular carcinoma (HCC). Those carriers in China account for 33% of all chronic carriers globally. A big epidemiological study of patients with chronic hepatitis B has revealed that baseline HBV DNA level or cirrhosis is an independent predictor for the occurrence of HCC.

Antroquinonol is a new chemical entity isolated from the mycelium of Antrodia camphorata, which showed interesting anticancer and anti-inflammatory activities.Previous studies have indicated that signaling molecules, such as PI3K, AMPK, and mTOR, participate in Antroquinonol-induced cancer cell death, whereas Nrf2 and NF-kB are involved in the anti-inflammatory effects of Antroquinonol. Moreover, we also found the administration of Antroquinonol also differentially modulated T cell activity and reduced IL-18 production, but enhanced the activation of Nrf2 and, thus, suppressed oxidative stress by animal studies. These results demonstrate the potential applications of Antroquinonol in treating hepatitis B.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Taiwan
  • Taichung, Taiwan
    • Chung Shan Medical University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Chronic HBV infection patients between the ages of 20 and 75 years with serum hepatitis B surface antigen(HBsAg) positivity for more than 6 months
2. BMI≦35
3. HBsAg≧10 IU/mL and HBV DNA≧2000 IU/mL.
4. AST or ALT≧25 IU and ALT<5xULN
5. Female subject must use effective methods of contraception.
6. No abnormal finding of clinical relevance
7. Written informed consent

Exclusion Criteria:

1. Evidence of hepatic decompensation such as:

   1. Coagulopathy defined as prolongation of prothrombin time greater than 3 seconds
   2. Total bilirubin of 2 times the upper limit of normal
   3. FIB-4 of 3.25 or greater
2. Abnormal hematological and biochemical parameters at screening A、 White blood cell count less than 2500 cells/uL B、 Absolute neutrophil count (ANC) less than 1,000 cells/mm3 (less than 750 mm3 for African or African-American subjects) C、 Hemoglobin less than 12 g/dL for males, less than 11 g/dL for females D、 Estimated GFR less than 50 mL/min
3. Suspected or confirmed liver diseases from etiologies other than HBV (such as alcohol, toxin, drug, shock, acute viral hepatitis A or E), co-infection with human immunodeficiency virus, hepatitis C virus or hepatitis delta virus, prior antiviral treatment with NUCs or interferon, and recent immunosuppressive therapy (including chemotherapy and systemic corticosteroid).
4. Immunodeficiency disorders or severe autoimmune disease
5. Severe pulmonary disorders or significant cardiac diseases
6. Gastrointestinal disorder with post-operative condition that could interfere with drug absorption
7. Significant psychiatric illness that in the judgment of the Investigator, is a contraindication to protocol participation or impairs a volunteer's ability to give informed consent
8. Any malignancy diagnosed within 5 years or evidence of hepatocellular carcinoma (e.g., α fetoprotein > 50ng/mL or radiologic evidence)
9. Solid organ transplantation
10. Current drug or alcohol abuse
11. Pregnancy or lactation
12. Under hepatitis B antiviral or interferon treatment within 3 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antroquinonol 100 mg PO BID; Antroquinonol (Hocena) 50mg/capsule. 2 capsules antroquinonol, twice a day.	Drug: Antroquinonol; Antroquinonol will be provided as a capsule-shaped which contain 50 mg Antroquinonol.; Other Names: Hocena
Experimental: Antroquinonol 50 mg PO BID; Antroquinonol (Hocena) 50mg/capsule. 1 capsule antroquinonol and 1 capsule placebo,twice a day.	Drug: Antroquinonol; Antroquinonol will be provided as a capsule-shaped which contain 50 mg Antroquinonol.; Other Names: Hocena; Other: placebo; The matching placebo will be packaged as Antroquinonol with appearance identical in all aspects
Placebo Comparator: Placebo; Placebo capsule, 2 capsules placebo, twice a day	Other: placebo; The matching placebo will be packaged as Antroquinonol with appearance identical in all aspects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage	The percentage improvement between baseline and day 85 in quantitative HBsAg.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IU/mL	Sserum hapatitis B virus DNA level	4 week
score	The Fibrosis-4 score helps to estimate the amount of scarring in the liver	12 week
Unit/L	Glutamic Oxaloacetic Transaminase	4 week
Unit /L	Glutamic Pyruvic Transaminase	4 week

Collaborators and Investigators

• Sponsor: Golden Biotechnology Corporation
• Investigators: Principal Investigator: Ching-Pin Lin, MD, Chung Shan Medical University

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Actual): June 16, 2023
• Study Completion (Actual): June 16, 2023

Study Registration Dates

• First Submitted: August 5, 2018
• First Submitted That Met QC Criteria: August 7, 2018
• First Posted (Actual): August 10, 2018

Study Record Updates

• Last Update Posted (Actual): September 13, 2023
• Last Update Submitted That Met QC Criteria: September 11, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Antroquinonol; Hocena
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Disease Attributes; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis; Chronic Disease; Hepatitis B; Hepatitis B, Chronic
• Other Study ID Numbers: GHHBV-2-001

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