A Clinical Trials to Evaluate the Efficacy and Safety of Tenofovir With and Without DWPUR001 in Patients With HBV

Study Overview
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Brief Summary
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The patient who meets the inclusion/exclusion criteria is assigned to Test1 group or Test 2 group or control group randomly. All subjects take one pill of Viread® Tab. (Tenofovir Disoproxil Fumarate 300mg) once a day for 48 weeks. At the same time, all randomized subjects take two pills of DWPUR001 or Placebo of DWPUR001 twice a day for 48 weeks.

Official Title
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An Exploratory, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Efficacy and Safety of Tenofovir With and Without DWPUR001 in Patients With Hepatitis B Virus(HBV)

Conditions
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Hepatitis; Virus, Chronic, Type B

Intervention / Treatment
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* Drug: DWPUR001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients at the age in between 19 and 69 years at the time of agreement Patients who had HBsAg-positive at least within 24 weeks or had a diagnosis with chronic hepatic disease by image test within 24 weeks from the time of screening. Patients who had HBeAg-positive and HBV DNA level≥20,000 IU/mL, or HBeAg-negative and HBV DNA level≥2,000 IU/mL Patients never treated with Tenofovir Patients whose ALT level is more than 2 times of UNL at the time of screening Patients prothrombin time prolonged≤4sec at the time of screening Patients Total bilirubin level≤3.0mg/dL at the time of screening Patients albumin level≥3.0g/dL at the time of screening Patients ELF score≥8.5 at the time of screening Patients who agree with the clinical trial voluntarily and sign on the agreement Exclusion Criteria: HIV, HCV or HDV infedted patients Patients who have abnormal liver function caused by other diseases (e.g. hematochromatosis, Wilson's disease, alcoholic hepatitis, Nonalcoholic steatohepatitis, alpha 1 antitrypsin deficiency) Patients who had suffered from variceal haemorrhage or hepatic encephalopathy Patients who need/had liver transplant Patients who have severe biliary obstruction, fulminant hepatic failure, radio-opacity gallstone, non-functional gall bladder, acute cholecystitis, Lactic acidosis/ adiposis Patients who have enteritis and colitis like peptic ulcer or Crohn's disease Patients who have significant kidney disease, cardiovascular disease, lung disease, nervous disease, self-immune disease, bone disease (ex: osteomalacia, osteopenia, chronic osteomyelitis, osteopsathyrosis, osteochondrosis, multiple fracture) or malignant tumor. Patients who have systemic infection Patients who have hypersensitivity to ursodeoxycholic acid or Tenofovir Patients who have the generic problem as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption Patients described as below at the time of screening Hb<8g/dL eGFR<60mL/min/1.73m2 AFP level>200ng/mL or had a diagnosis with hepatocellular carcinoma based on the radiology result within 24 weeks Patients who had immune- or cytokine-based antiviral agents treatment (ex. Interferon α, Peginterferon α), or immunosuppression therapy (ex. Cyclosporine, Tacrolimus) in 24 weeks at the time of screening Patients who have to use the contraindication of comedication drugs during clinical trial or can't get the wash-out period Women of child-bearing potential not using an effective birth control method Patients who have psychiatric disorders or drug or alcohol abuse, so can't understand the purpose and process of this clinical trial Patients who participated in other clinical trial in 30 days prior to the enrollment in this study Patients who were determined inappropriate by the investigator to participate in this study

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 69 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tenofovir 300mg qd + DWPUR001 500mg bid<br>Tenofovir 300mg qd + DWPUR001 500mg bid for up to 12 months | Drug: DWPUR001<br> <br> |
| Experimental: Tenofovir 300mg qd + DWPUR001 300mg bid<br>Tenofovir 300mg qd + DWPUR001 300mg bid for up to 12 months | Drug: DWPUR001<br> <br> |
| Placebo Comparator: Tenofovir 300mg qd + DWPUR001 Placebo bid<br>Tenofovir 300mg qd + DWPUR001 Placebo bid for up to 12 months | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of normalization of ALT level (≤1× ULN)(%) |  | At the 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of normalization of ALT level (≤1× ULN)(%) |  | At the 2, 8, 12, 24, 36, 48 weeks | 
| The change of fibrosis marker(ELF score) compared with the baseline |  | At the 48 weeks | 
| The change of immunological marker(PD-1, CTLA-4, FoxP3) compared with baseline |  | At the 12, 24, 48 weeks | 
| The change of anti-oxidant/anti-inflammatory marker(SOD, MDA, TNF-α) |  | At the 24, 48 weeks | 
| The change of HBV DNA level compared with baseline (IU/mL) |  | At the 12, 24, 36, 48 weeks |