Clinical trial NCT03625102: A Randomized, Double-Blind Trial of Antroquinonol in Patients With Chronic Hepatitis B
Official title: A Randomized, Double-Blind, Dosing-Ranging, Placebo-controlled Trial of Antroquinonol in Patients With Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HBV
Keywords: Antroquinonol
Hocena
Lead sponsor: Golden Biotechnology Corporation
Sponsor class: INDUSTRY
First posted: 2018-08-10
Enrollment: 60
Sex: ALL
Minimum age (years): 20
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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:

1. Antroquinonol 100 mg PO BID
2. Antroquinonol 50 mg PO BID
3. Placebo
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage
timeFrame: 12 weeks
Secondary outcomes:
measure: IU/mL
timeFrame: 4 week
measure: score
timeFrame: 12 week
measure: Unit/L
timeFrame: 4 week
measure: Unit /L
timeFrame: 4 week
Other outcomes:
Locations:
city: Taichung
country: Taiwan
facility: Chung Shan Medical University Hospital
Study officials:
affiliation: Chung Shan Medical University
name: Ching-Pin Lin, MD
role: PRINCIPAL_INVESTIGATOR
References: