Clinical trial NCT02966964: A Clinical Trials to Evaluate the Efficacy and Safety of Tenofovir With and Without DWPUR001 in Patients With HBV
Official title: 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)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Hepatitis; Virus, Chronic, Type B
Lead sponsor: Uijeongbu St. Mary Hospital
Sponsor class: OTHER
Collaborators: name: Daewoong Pharmaceutical Co. LTD.
First posted: 2016-11-17
Enrollment: 90
Sex: ALL
Minimum age (years): 19
Maximum age (years): 69
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

1. Patients at the age in between 19 and 69 years at the time of agreement
2. 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.
3. Patients who had HBeAg-positive and HBV DNA level≥20,000 IU/mL, or HBeAg-negative and HBV DNA level≥2,000 IU/mL
4. Patients never treated with Tenofovir
5. Patients whose ALT level is more than 2 times of UNL at the time of screening
6. Patients prothrombin time prolonged≤4sec at the time of screening
7. Patients Total bilirubin level≤3.0mg/dL at the time of screening
8. Patients albumin level≥3.0g/dL at the time of screening
9. Patients ELF score≥8.5 at the time of screening
10. Patients who agree with the clinical trial voluntarily and sign on the agreement

Exclusion Criteria:

1. HIV, HCV or HDV infedted patients
2. Patients who have abnormal liver function caused by other diseases (e.g. hematochromatosis, Wilson's disease, alcoholic hepatitis, Nonalcoholic steatohepatitis, alpha 1 antitrypsin deficiency)
3. Patients who had suffered from variceal haemorrhage or hepatic encephalopathy
4. Patients who need/had liver transplant
5. Patients who have severe biliary obstruction, fulminant hepatic failure, radio-opacity gallstone, non-functional gall bladder, acute cholecystitis, Lactic acidosis/ adiposis
6. Patients who have enteritis and colitis like peptic ulcer or Crohn's disease
7. 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.
8. Patients who have systemic infection
9. Patients who have hypersensitivity to ursodeoxycholic acid or Tenofovir
10. Patients who have the generic problem as galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
11. 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
12. 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
13. Patients who have to use the contraindication of comedication drugs during clinical trial or can't get the wash-out period
14. Women of child-bearing potential not using an effective birth control method
15. Patients who have psychiatric disorders or drug or alcohol abuse, so can't understand the purpose and process of this clinical trial
16. Patients who participated in other clinical trial in 30 days prior to the enrollment in this study
17. Patients who were determined inappropriate by the investigator to participate in this study

Primary outcomes:
measure: The proportion of normalization of ALT level (≤1× ULN)(%)
timeFrame: At the 4 weeks
Secondary outcomes:
measure: The proportion of normalization of ALT level (≤1× ULN)(%)
timeFrame: At the 2, 8, 12, 24, 36, 48 weeks
measure: The change of fibrosis marker(ELF score) compared with the baseline
timeFrame: At the 48 weeks
measure: The change of immunological marker(PD-1, CTLA-4, FoxP3) compared with baseline
timeFrame: At the 12, 24, 48 weeks
measure: The change of anti-oxidant/anti-inflammatory marker(SOD, MDA, TNF-α)
timeFrame: At the 24, 48 weeks
measure: The change of HBV DNA level compared with baseline (IU/mL)
timeFrame: At the 12, 24, 36, 48 weeks
Other outcomes:
Locations:
city: Ansan-si
country: Korea, Republic of
facility: Korea University Ansan Hospital
city: Bundang
country: Korea, Republic of
facility: Bundang CHA medical center
city: Incheon
country: Korea, Republic of
facility: Incheon St. Mary Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital
city: Suwon-si
country: Korea, Republic of
facility: Ajou University Medical Center
city: Uijongbu
country: Korea, Republic of
facility: Uijeongbu St. Mary Hospital
Study officials:
References: