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

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)

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.

Study Overview

• Status: Unknown
• Conditions: Hepatitis; Virus, Chronic, Type B
• Intervention / Treatment: Drug: Placebo; Drug: DWPUR001

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Chang Wook Kim, M.D., Ph.D.; Phone Number: +82-31-847-2719; Email: cwkim@catholic.ac.kr

Study Locations

• Korea, Republic of
  • Ansan-si, Korea, Republic of
    • Recruiting
    • Korea University Ansan Hospital
  • Bundang, Korea, Republic of
    • Recruiting
    • Bundang Cha Medical Center
  • Incheon, Korea, Republic of
    • Recruiting
    • Incheon St. Mary Hospital
  • Seoul, Korea, Republic of
    • Recruiting
    • Severance Hospital
  • Suwon-si, Korea, Republic of
    • Recruiting
    • Ajou University Medical Center
  • Uijongbu, Korea, Republic of
    • Recruiting
    • Uijeongbu St. Mary Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 69 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Uijeongbu St. Mary Hospital
• Collaborators: Daewoong Pharmaceutical Co. LTD.

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Anticipated): November 1, 2018
• Study Completion (Anticipated): February 1, 2019

Study Registration Dates

• First Submitted: November 15, 2016
• First Submitted That Met QC Criteria: November 15, 2016
• First Posted (Estimate): November 17, 2016

Study Record Updates

• Last Update Posted (Actual): September 25, 2017
• Last Update Submitted That Met QC Criteria: September 21, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis B, Chronic
• Other Study ID Numbers: EURECA001