Phase 3 Study of Besifovir
This study is not yet open for participant recruitment.
Verified September 2013 by IlDong Pharmaceutical Co Ltd
Sponsor:
IlDong Pharmaceutical Co Ltd
Information provided by (Responsible Party):
IlDong Pharmaceutical Co Ltd
ClinicalTrials.gov Identifier:
NCT01937806
First received: September 4, 2013
Last updated: September 23, 2013
Last verified: September 2013
History of Changes作者: tonychant 时间: 2013-12-22 21:43
Purpose
To prove that a study drug is noninferior to a control drug with a proportion of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) at the 48th week after 48-week administration of Besifovir 150 mg, or Tenofovir 300 mg as a control drug to chronic hepatitis B patients
Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Phase Ⅲ, Multi-center, Randomized, Double-blinded, Parallel Study to Assess the Antiviral Activity and Safety of Besifovir 150 mg Compared to Tenofovir 300 mg in Chronic Hepatitis B Patients for 48 Weeks
Resource links provided by NLM:
MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis B
Drug Information available for: Tenofovir Tenofovir Disoproxil Fumarate
U.S. FDA Resources
Further study details as provided by IlDong Pharmaceutical Co Ltd:
Primary Outcome Measures:
The rate of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) at the 48th week [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
The rate of subjects who showed HBV DNA less than 116 copies/mL (20 IU/mL, LOQ of COBAS TaqManTM) at the 48th week [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
Average amount of change in an HBV DNA common logarithm value at the 48th week to a base value [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
The rate of subjects who showed ALT normalized at the 48th week [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
The rate of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) and ALT normalized at the 48th week [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
The rate of subjects who showed HBsAg serum loss and/or seroconversion (HBsAg loss and Anti-HBs formation) at the 48th week [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
The rate of subjects who showed HBeAg serum loss and/or seroconversion (HBeAg loss and Anti-HBe formation) at the 48th week among subjects with positive HBeAg [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
The rate of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) and HBeAg loss at the 48th week among subjects with positive HBeAg [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
The rate of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) and HBeAg seroconversion at the 48th week among subjects with positive HBeAg [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
Changes in antiviral drug resistant mutation according to HBV DNA sequencing results at the 48th week [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
The rate of subjects who showed virologic breakthrough according to serum HBV DNA at the 48th week [ Time Frame: at the 48th week ] [ Designated as safety issue: No ]
Estimated Enrollment: 188
Study Start Date: October 2013
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: besifovir 150mg
Besifovir 150 mg q.d. + Placebo of Tenofovir Disoproxil Fumarate 300 mg q.d. + L-carnitine (L-Carn Tab. 330 mg) 660 mg q.d.
Drug: besifovir 150mg
Besifovir 150 mg q.d. + Placebo of Tenofovir Disoproxil Fumarate 300 mg q.d. + L-carnitine (L-Carn Tab. 330 mg) 660 mg q.d.
Active Comparator: Tenofovir 300mg
Placebo of Besifovir 150 mg q.d. + Tenofovir Disoproxil Fumarate 300 mg q.d. + Placebo of L-carnitine (L-Carn Tab. 330 mg) 660 mg q.d.
Drug: tenofovir 300mg
Placebo of Besifovir 150 mg q.d. + Tenofovir Disoproxil Fumarate 300 mg q.d. + Placebo of L-carnitine (L-Carn Tab. 330 mg) 660 mg q.d.
Detailed Description:
Screening Period Subject registration is conducted with confirming selection and exclusion criteria after a written consent form is obtained within 28 days before clinical trial drug administration.
Wash-out Period Subjects who had been treated with antiviral agents within 12 weeks should complete a 4-week wash-out period from the stage of stopping antiviral agent treatment before a baseline visit and subjects who have no experience of antiviral agent treatment start a baseline visit without a wash-out period.
Baseline Subjects who visit on the date of starting clinical trial drug administration are randomized to a test group or a control group at a ratio of 1:1. Double blindness is applied for both groups.
Treatment period Subjects are orally administered with a clinical trial drug q.ds.i.d. for 48 weeks and visit at the 0, 4th, 12th, 24th, 36th, and 48th week for an HBV DNA test, laboratory tests, a physical test, vital signs, and adverse events.
Follow-up period Subjects are provided with appropriate treatment after completing the 48-week trial or dropping out. Subjects visit once at the 60th week for follow-up of adverse events, such as acute deterioration of hepatitis B, and HBV DNA test results. If any treatment is not conducted after 48-week administration, subjects visit at intervals of four weeks until a follow-up visit (60th week) and the same tests with the 24th week visit (Visit 5) are conducted. However, subjects who participate in a 48-week separate extended trial conducted after 48-week administration in this clinical trial do not have a follow-up period.
Eligibility
Ages Eligible for Study: 20 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
Male or female patients over the age of 20 years old
Patients who show positive HBsAg or has a history of chronic hepatitis B for the last six months or more before screening
Patients who have not received interferon (including Pegylation formulation) to treat chronic hepatitis and antiviral agents for more than 12 weeks.
Patients who showed positive HBsAg during screening
Patients who showed HBV DNA measured by COBAS TaqManTM HBV Test more than 1x105 copies/mL (17,241 IU/mL) in case of positive HBeAg during screening, or who showed HBV DNA measured by COBAS TaqManTM HBV Test more than 1x104 copies/mL (1,724 IU/mL) in case of negative HBeAg
Patients who showed ALT more than 1.2 times, or less than 10 times of the upper limit in the normal range during screening
Patients who were explained about the purpose, methods and effects of the clinical trial and then, signed a written consent form.
Male and female patients of childbearing age who can use double contraception acknowledged* during a trial period * Double contraception acknowledged means combination of barrier contraception (condom, diaphragm, etc.) and other contraception (sterilization operation, intrauterine contraceptive device, oral contraceptive drug, other hormone delivery system, contraceptive cream, jelly or foam, etc.).
Exclusion Criteria:
Patients who have hepatitis C (HCV), hepatitis D (HDV), or human immunodeficiency virus (HIV)
Patients with a uncompensated liver disease who have at least one of the following values or signs during screening
Total bilirubin > 2 x ULN
Prothrombin time delayed more than three seconds compared to the normal value
Serum Albumin < 30 g/L (3 g/dL)
A medical history of ascites, jaundice, hemorrhage by varix, hepatic encephalopathy, or other signs of liver function loss
At least one of the following laboratory values during screening
Hemoglobin < 9.0 g/dL
Absolute neutrophil count (ANC) < 1.5 x 109 /L (1500 /mm3)
Platelet count < 100 x 109 /L (100 x 103 /mm3)
Serum creatinine > 1.5 mg/dL
Serum amylase > 2 x ULN and Lipase > 2 x ULN
Patients who showed GFR less than 50 mL/min by calculating MDRD (Modification of Diet in Renal Disease: 1.86 x PCr -1.154 x AGE -0.203 (x 0.742 for women)) during screening
Patients who showed alpha-fetoprotein(AFP) more than 50 ng/mL during screening and are estimated to have hepatocellular carcinoma (HCC) through liver/abdomen CT scans
Patients who had received the following drugs for the last two months before screening (however, short-term use (less than consecutive 14 days) of these drugs and low-dose aspirin (100 mg, maximally, 300 mg/day) are allowed.)
Nephrotoxic drugs (e.g. Aminoglycosides, Amphotericin B, NSAIDs)
Hepatotoxic drugs (e.g. Erythromycin, Ketoconazole, Rifampin, Fluconazole, Dapsone)
Anticoagulant (e.g. Warfarin)
Patients who are suspected by an investigator to have the level of immunity decreased among patients who had been administered with immunosuppressants within six months before screening
Patients who had been administered with long-term general corticosteroids (more than consecutive 14 days) at a high dose (more than prednisolone 20 mg daily*) within three months before screening (In case of local corticosteroids, an investigator decides it.) * It is equal to cortisone 125 mg, hydrocortisone 100 mg, prednisone 20 mg, methylprednisolone 16 mg, triamcinolone 16 mg, dexamethasone 3 mg, betamethasone 2.4 mg.
Patients who were diagnosed as a malignant tumor within five years before screening or have a relapse of a malignant tumor (In case of a benign tumor, if an investigator decides that it does not affect the progress of the clinical trial during a trial period, the patients can be registered.)
Patients who are scheduled to participate in other clinical trial after registered in this clinical trial, or had been participated in other clinical trial within three months before registered in this clinical trial
Pregnant women, lactating women, or patients who planned pregnancy during a trial period
Patients who have hypersensitivity to the clinical trial drug in this clinical trial
Patients who have a past medical history of clinical alcohol or drug abuse within a year before screening or now are abusers
Patients who have a severe disease, such as liver diseases, heart failure, renal failure, and pancreatitis, decided by an investigator to have an effect on this clinical trial
Patients who have other hepatic diseases (hematochromatosis, Wilson's disease, alcoholic liver diseases, nonalcoholic steatohepatitis, α1-antitrypsin deficiency) except hepatitis B
Patients who received an organ transplant
Persons who are possible to decline daily function due to a mental disease or patients who are not able to understand the purpose and methods of this clinical trial
Patients who are decided by an investigator as unsuitable for conducting this clinical trial
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01937806
Locations
Korea, Republic of
Soonchunhyang University Hospital Not yet recruiting
Cheonan, Chungchoengnam-do, Korea, Republic of
Contact: Hong Soo Kim, M.D., Ph.D.
Principal Investigator: Hong Soo Kim, M.D., Ph.D.
Hallym University Medical Center Not yet recruiting
ChunCheon, Kangwon-do, Korea, Republic of
Contact: Dong Joon Kim, M.D., Ph.D.
Principal Investigator: Dong Joon Kim, M.D., Ph.D.
Wonju Sevrerance Christian Hospital Not yet recruiting
Wonju, Kangwon-do, Korea, Republic of
Contact: Moon Young Kim, M.D., Ph.D.
Principal Investigator: Moon Young Kim, M.D., Ph.D.
Korea University Medical Center Not yet recruiting
Ansan, Kyounggi-do, Korea, Republic of
Contact: Hyung Joon Yim, M.D., Ph.D.
Principal Investigator: Hyung Joon Yim, M.D., Ph.D.
Hanyang University Guri Hospital Not yet recruiting
Guri, Kyunggi-do, Korea, Republic of
Contact: Joo Hyun Sohn, M.D., Ph.D.
Principal Investigator: Joo Hyun Sohn, M.D., Ph.D.
Ajou University Medical Center Not yet recruiting
Suwon,, Kyunggi-do, Korea, Republic of
Contact: Jae-Youn Cheong, M.D., Ph.D.
Principal Investigator: Jae-Youn Cheong, M.D., Ph.D.
Kyungpook National University Hospital Not yet recruiting
Daegu, Korea, Republic of
Contact: Young Oh Kweon, M.D., Ph.D.
Principal Investigator: Young Oh Kweon, M.D.,Ph.D
Chungnam National University Hospital Not yet recruiting
Daejeon, Korea, Republic of
Contact: Byung Seok Lee, M.D., Ph.D.
Principal Investigator: Byung Seok Lee, M.D., Ph.D.
Inha University Hospital Not yet recruiting
Incheon, Korea, Republic of
Contact: Jin-Woo Lee, M.D., Ph.D.
Principal Investigator: Jin-Woo Lee, M.D., Ph.D.
Inje University Busan Paik Hospital Not yet recruiting
Pusan, Korea, Republic of
Contact: Sung Jae Park, M.D., Ph.D.
Principal Investigator: Sung Jae Park, M.D., Ph.D.
The Catholic University of Korea, Seoul St. Vincent's Hospital Not yet recruiting
Seoul, Korea, Republic of
Contact: JinMo Yang, M.D., Ph.D.
Principal Investigator: JinMo Yang, M.D., Ph.D.
Asan Medical Center Not yet recruiting
Seoul, Korea, Republic of
Contact: Young-Suk Lim, M.D., Ph.D.
Principal Investigator: Young-Suk Lim, M.D., Ph.D.
Seoul National University Hospital Not yet recruiting
Seoul, Korea, Republic of
Contact: Yoon Jun Kim, M.D., Ph.D.
Sub-Investigator: Yoon Jun Kim, M.D., Ph.D.
Gangnam Severance Hospital Not yet recruiting
Seoul, Korea, Republic of
Contact: Kwan Sik Lee, M.D., Ph.D.
Principal Investigator: Kwan Sik Lee, M.D., Ph.D.
Soonchunhyang University Hospital Not yet recruiting
Seoul, Korea, Republic of
Contact: Jang, Jae Young, M.D., Ph.D.
Principal Investigator: Jae Young Jang, M.D., Ph.D.
Severance Hospital of Yonsei University Not yet recruiting
Seoul, Korea, Republic of
Contact: Kwang-Hyub Han, M.D., Ph.D.
Principal Investigator: Kwang-Hyub Han, M.D., Ph.D.
The Catholic University of Korea, Seoul St. Mary's Hospital Not yet recruiting
Seoul, Korea, Republic of
Contact: Seung Kew Yoon, M.D., Ph.D.
Principal Investigator: Seung Kew Yoon, M.D., Ph.D.
Seoul National University Boramae medical Center Not yet recruiting
Seoul, Korea, Republic of
Contact: Won Kim, M.D., Ph.D.
Principal Investigator: Won Kim, M.D., Ph.D.
Korea University Medical Center Not yet recruiting
Seoul, Korea, Republic of
Contact: Soon Ho Um , M.D., Ph.D.
Principal Investigator: Soon Ho Um, M.D., Ph.D.
Ulsan University Hospital, Not yet recruiting
Ulsan, Korea, Republic of
Contact: Neung Hwa Park, M.D., Ph.D.
Principal Investigator: Neung Hwa Park, M.D., Ph.D. 作者: StephenW 时间: 2013-12-22 22:01
