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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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HBV

Intervention / Treatment
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* Drug: Antroquinonol
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 BMI≦35 HBsAg≧10 IU/mL and HBV DNA≧2000 IU/mL. AST or ALT≧25 IU and ALT<5xULN Female subject must use effective methods of contraception. No abnormal finding of clinical relevance Written informed consent Exclusion Criteria: Evidence of hepatic decompensation such as: Coagulopathy defined as prolongation of prothrombin time greater than 3 seconds Total bilirubin of 2 times the upper limit of normal FIB-4 of 3.25 or greater 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 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). Immunodeficiency disorders or severe autoimmune disease Severe pulmonary disorders or significant cardiac diseases Gastrointestinal disorder with post-operative condition that could interfere with drug absorption 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 Any malignancy diagnosed within 5 years or evidence of hepatocellular carcinoma (e.g., α fetoprotein > 50ng/mL or radiologic evidence) Solid organ transplantation Current drug or alcohol abuse Pregnancy or lactation Under hepatitis B antiviral or interferon treatment within 3 months

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a single-center, phase IIa, double blind, and randomized, placebo-controlled trial of Antroquinonol in patients with hepatitis B infection. Subjects with diagnosis of hepatitis B meet inclusion/exclusion criteria will be randomized into 3 groups: Antroquinonol 100 mg PO BID Antroquinonol 50 mg PO BID Placebo
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antroquinonol, Hocena