A Randomized, Placebo-controlled Trial of Antroquinonol in Patients With Chronic Hepatitis B

Study Overview
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Brief Summary
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Primary Objective: To evaluate the activity of Antroquinonol in patients with chronic hepatitis B Secondary Objective: To assess the mechanism and cytokines change of Antroquinonol in patients with chronic hepatitis B

Detailed Description
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This is a Phase II, three-arms, double-blind, dosing-ranging, placebo-controlled trial evaluating the efficacy of Antroquinonol in patients with chronic hepatitis B. The study is conducted in compliance with the guidelines for Good Clinical Practice and the Declaration of Helsinki. Approval is obtained from the local ethics committee or institutional review board at each study center. All the patients provided written informed consent. 60 patients totally (20 patients per arm) with chronic hepatitis B will receive Antroquinonol or placebo. A patient will have received at one dose of Antroquinonol or placebo. Enrollment will continue until the target number of evaluable patients has been enrolled. Written informed consent must be obtained from all patients before initiating Screening. The Screening period will be up to 14 days in duration (Days -14 to -1). Following completion of all Screening assessments and confirmation of eligibility criteria, patients will receive Antroquinonol 100mg, 200mg or placebo per day on Day 1 for 12 weeks or until documented evidence of virus DNA > 10 x [minimum], unacceptable toxicity, non-compliance or withdrawal of consent by the patient, or the investigator decides to discontinue treatment, whichever comes first. The time of study drug administration should be recorded in the patient diary. Patients will attend study visits on Days 1, 29, 57 and 85. The following procedures will be performed according to the schedule of assessments: physical examination, vital signs, clinical laboratory tests, adverse events (AEs), concomitant medication and patient compliance. The primary endpoint is the change from baseline in quantitative hepatitis B surface antigen (Log qHBsAg) at Day 85.

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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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Antroquinonol capsule 100mg
* Drug: Antroquinonol capsule 200mg
* Drug: Placebo oral capsule


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. GOT or GPT ≧ 25 IU 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 White blood cell count less than 2500 cells/uL Absolute neutrophil count (ANC) less than 1,000 cells/mm3 (less than 750 mm3 for African or African-American subjects) Hemoglobin less than 12 g/dL for males, less than 11 g/dL for females 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
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antroquinonol capsule 100mg<br>Patients will receive 12-week of 50mg BID Antroquinonol | Drug: Antroquinonol capsule 100mg<br>* Patients will receive 12-week of 50mg BID Antroquinonol<br>* Other names: Antroquinonol 100mg;|
| Experimental: Antroquinonol capsule 200mg<br>Patients will receive 12-week of 100mg BID Antroquinonol | Drug: Antroquinonol capsule 200mg<br>* Patients will receive 12-week of 100mg BID Antroquinonol<br>* Other names: Antroquinonol 200mg;|
| Placebo Comparator: Placebo oral capsule<br>Patients will receive 12-week of 50mg BID Antroquinonol placebo | Drug: Placebo oral capsule<br>* Patients will receive 12-week of 100mg BID Antroquinonol placebo<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| quantitative hepatitis B surface antigen (Log qHBsAg) | The primary endpoint is the change from baseline in quantitative hepatitis B surface antigen (Log qHBsAg) at Week 12. | Week 0 and Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum hapatitis B virus DNA level | Change from baseline serum hapatitis B virus DNA level(HBV DNA as measured in IU/mL) at Week 4, Week 8 and Week 12 | Week 0, Week 4, Week 8 and Week 12 | 
| hepatitis B surface antigen | Change from baseline quantitative hepatitis B surface antigen at Week 4 and Week 8 | Week 0, Week 4 and Week 8 | 
| Fibrosis-4(FIB-4) scale | Changes from baseline FIB-4 scale at Week 12 | Week 0 and Week 12 | 
| Hepatitis B surface antigen loss (HBeAg loss) | Percentage of HBeAg loss at Week 12 | Week 12 | 
| glutamate oxaloacetate transaminase (GOT) | Change from baseline GOT at Week 12 | Week 0 and Week 12 | 
| Glutamic Pyruvic Transaminase (GPT) | Change from baseline GPT at Week 12 | Week 0 and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antroquinonol, Chronic Hepatitis B