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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| besifovir 150mg | Experimental | 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. |
|
| Tenofovir 300mg | Active Comparator | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| besifovir 150mg | Drug | 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. |
|
| Measure | Description | Time Frame |
|---|---|---|
| The rate of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) at the 48th week | The rate of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) at the 48th week | at the 48th week |
| Measure | Description | Time Frame |
|---|---|---|
| The rate of subjects who showed HBV DNA less than 116 copies/mL (20 IU/mL, LOQ of COBAS TaqManTM) at the 48th week | The rate of subjects who showed HBV DNA less than 116 copies/mL (20 IU/mL, LOQ of COBAS TaqManTM) at the 48th week | at the 48th week |
| Average amount of change in an HBV DNA common logarithm value at the 48th week to a base value |
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Inclusion Criteria:
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
At least one of the following laboratory values during screening
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.)
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
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| Name | Affiliation | Role |
|---|---|---|
| Kwan Sik Lee, M.d., Ph.D | Kangnam Severance Hospital, Yonsei University, Seoul, Korea | Principal Investigator |
| Young Oh Kweon, M.D., Ph.D | Kyungpook National University Hospital, Seoul, Korea | Principal Investigator |
| Hyung Joon Yim, M.D., Ph.D. | Korea University Medical Center, Ansan, Kyunggi-do, Korea | Principal Investigator |
| Soon Ho Um, M.D., Ph.D. | Korea University Medical Center, Seoul, Korea | Principal Investigator |
| Won Kim, M.D., Ph.D. | Seoul National University Boramae medical Center, Seoul, Korea | Principal Investigator |
| Sung Jae Park, M.D., Ph.D. | Inje University Busan Paik Hospital, Pusan, Korea | Principal Investigator |
| Yoon Jun Kim, M.D., Ph.D. | Seoul National University Hospital, Seoul, Korea | Principal Investigator |
| Yoon Jun Kim, M.D., Ph.D. | The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Korea | Principal Investigator |
| Young-Suk Lim, M.D., Ph.D. |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Soonchunhyang University Hospital | Cheonan | Chungchoengnam-do | South Korea | |||
| Hallym University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38473248 | Derived | Yim HJ, Kang SH, Jung YK, Ahn SH, Kim W, Yang JM, Jang JY, Kweon YO, Cho YK, Kim YJ, Hong GY, Kim DJ, Sohn JH, Lee JW, Park SJ, Yim SY, Park JK, Um SH. Reduced Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Receiving Long-Term Besifovir Therapy. Cancers (Basel). 2024 Feb 22;16(5):887. doi: 10.3390/cancers16050887. | |
| 33493393 |
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| tenofovir 300mg | Drug | 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. |
|
Average amount of change in an HBV DNA common logarithm value at the 48th week to a base value |
| at the 48th week |
| The rate of subjects who showed ALT normalized at the 48th week | The rate of subjects who showed ALT normalized at the 48th week | at the 48th week |
| The rate of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) and ALT normalized at the 48th week | The rate of subjects who showed HBV DNA undetected (less than 400 copies/mL (69 IU/mL)) and ALT normalized at the 48th week | at the 48th week |
| The rate of subjects who showed HBsAg serum loss and/or seroconversion (HBsAg loss and Anti-HBs formation) at the 48th week | The rate of subjects who showed HBsAg serum loss and/or seroconversion (HBsAg loss and Anti-HBs formation) at the 48th week | at the 48th week |
| 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 | 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 | at the 48th week |
| 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 | 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 | at the 48th week |
| 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 | 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 | at the 48th week |
| Changes in antiviral drug resistant mutation according to HBV DNA sequencing results at the 48th week | Changes in antiviral drug resistant mutation according to HBV DNA sequencing results at the 48th week | at the 48th week |
| The rate of subjects who showed virologic breakthrough according to serum HBV DNA at the 48th week | The rate of subjects who showed virologic breakthrough according to serum HBV DNA at the 48th week | at the 48th week |
| Asan Medical Center, Seoul, Korea |
| Principal Investigator |
| JinMo Yang, M.D., Ph.D. | The Catholic University of Korea, Seoul St. Vincent's Hospital, Seoul, Korea | Principal Investigator |
| Jang, Jae Young, M.D., Ph.D. | Soonchunhyang University Hospital, Seoul, Korea | Principal Investigator |
| Jae-Youn Cheong, M.D., Ph.D. | Ajou University Medical Center, Suwon, Kyunggi-do, Korea | Principal Investigator |
| Neung Hwa Park, M.D., Ph.D. | Ulsan University Hospital, Ulsan, Korea | Principal Investigator |
| Moon Young Kim, M.D., Ph.D. | Wonju Sevrerance Christian Hospital, Wonju, Kangwon-do, Korea | Principal Investigator |
| Jin-Woo Lee, M.D., Ph.D. | Inha University Hospital, Incheon, Inchen, Korea | Principal Investigator |
| Dong Joon Kim, M.D., Ph.D. | Hallym University Medical Center, ChunCheon, Kangwon-do, Korea | Principal Investigator |
| Byung Seok Lee, M.D., Ph.D. | Chungnam National University Hospital | Principal Investigator |
| Joo Hyun Sohn, M.D., Ph.D. | Hanyang University Guri Hospital, Guri, Kyunggi-do, Korea | Principal Investigator |
| Kwang-Hyub Han, M.D., Ph.D. | Severance Hospital of Yonsei University, Seoul, Korea | Principal Investigator |
| Hong Soo Kim, M.D., Ph.D. | Soonchunhyang University Hospital, Choenan, Chungchoengnam-do, Korea | Principal Investigator |
| Chuncheon |
| Gangwon-do |
| South Korea |
| Wonju Sevrerance Christian Hospital | Wŏnju | Gangwon-do | South Korea |
| Hanyang University Guri Hospital | Guri-si | Gyeonggi-do | South Korea |
| Ajou University Medical Center | Suwon | Gyeonggi-do | South Korea |
| Korea University Medical Center | Ansan | Kyounggi-do | South Korea |
| Kyungpook National University Hospital | Daegu | South Korea |
| Chungnam National University Hospital | Daejeon | South Korea |
| Inha University Hospital | Incheon | South Korea |
| Inje University Busan Paik Hospital | Pusan | South Korea |
| Asan Medical Center | Seoul | South Korea |
| Gangnam Severance Hospital | Seoul | South Korea |
| Korea University Medical Center | Seoul | South Korea |
| Seoul National University Boramae medical Center | Seoul | South Korea |
| Seoul National University Hospital | Seoul | South Korea |
| Severance Hospital of Yonsei University | Seoul | South Korea |
| Soonchunhyang University Hospital | Seoul | South Korea |
| The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | South Korea |
| The Catholic University of Korea, Seoul St. Vincent's Hospital | Seoul | South Korea |
| Ulsan University Hospital, | Ulsan | South Korea |
| Song DS, Kim W, Ahn SH, Yim HJ, Jang JY, Kweon YO, Cho YK, Kim YJ, Hong GY, Kim DJ, Jung YK, Sohn JH, Lee JW, Park SJ, Lee BS, Kim JH, Kim HS, Yoon SK, Kim MY, Lee KS, Lim YS, Lee WS, Yang JM, Kim KH, Han KH, Um SH. Continuing besifovir dipivoxil maleate versus switching from tenofovir disoproxil fumarate for treatment of chronic hepatitis B: Results of 192-week phase 3 trial. Clin Mol Hepatol. 2021 Apr;27(2):346-359. doi: 10.3350/cmh.2020.0307. Epub 2021 Jan 25. |
| 32355123 | Derived | Yim HJ, Kim W, Ahn SH, Yang JM, Jang JY, Kweon YO, Cho YK, Kim YJ, Hong GY, Kim DJ, Jung YK, Um SH, Sohn JH, Lee JW, Park SJ, Lee BS, Kim JH, Kim HS, Yoon SK, Kim MY, Lee KS, Lim YS, Lee WS, Han KH. Besifovir Dipivoxil Maleate 144-Week Treatment of Chronic Hepatitis B: An Open-Label Extensional Study of a Phase 3 Trial. Am J Gastroenterol. 2020 Aug;115(8):1217-1225. doi: 10.14309/ajg.0000000000000605. |
| 30448598 | Derived | Ahn SH, Kim W, Jung YK, Yang JM, Jang JY, Kweon YO, Cho YK, Kim YJ, Hong GY, Kim DJ, Um SH, Sohn JH, Lee JW, Park SJ, Lee BS, Kim JH, Kim HS, Yoon SK, Kim MY, Yim HJ, Lee KS, Lim YS, Lee WS, Park NH, Jin SY, Kim KH, Choi W, Han KH. Efficacy and Safety of Besifovir Dipivoxil Maleate Compared With Tenofovir Disoproxil Fumarate in Treatment of Chronic Hepatitis B Virus Infection. Clin Gastroenterol Hepatol. 2019 Aug;17(9):1850-1859.e4. doi: 10.1016/j.cgh.2018.11.001. Epub 2018 Nov 15. |
| ID | Term |
|---|---|
| D019694 | Hepatitis B, Chronic |
| ID | Term |
|---|---|
| D006509 | Hepatitis B |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D018347 | Hepadnaviridae Infections |
| D004266 | DNA Virus Infections |
| D014777 | Virus Diseases |
| D006525 | Hepatitis, Viral, Human |
| D006521 | Hepatitis, Chronic |
| D006505 | Hepatitis |
| D008107 | Liver Diseases |
| D004066 | Digestive System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| C487369 | ((1-((2-amino-9H-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonic acid dipivoxyl |
| D000068698 | Tenofovir |
| ID | Term |
|---|---|
| D063065 | Organophosphonates |
| D009943 | Organophosphorus Compounds |
| D009930 | Organic Chemicals |
| D000225 | Adenine |
| D011687 | Purines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
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