Phase 3 and Extensional Study of Besifovir

NCT ID: NCT01937806

Last Updated: 2020-01-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

197 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-31

Study Completion Date

2023-01-31

Brief Summary

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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

Detailed Description

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* 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.

Conditions

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Chronic Hepatitis B

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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.

Group Type EXPERIMENTAL

besifovir 150mg

Intervention Type 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.

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.

Group Type ACTIVE_COMPARATOR

tenofovir 300mg

Intervention Type 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.

Interventions

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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.

Intervention Type 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.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Male or female patients over the age of 20 years old
2. Patients who show positive HBsAg or has a history of chronic hepatitis B for the last six months or more before screening
3. Patients who have not received interferon (including Pegylation formulation) to treat chronic hepatitis and antiviral agents for more than 12 weeks.
4. Patients who showed positive HBsAg during screening
5. 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
6. Patients who showed ALT more than 1.2 times, or less than 10 times of the upper limit in the normal range during screening
7. Patients who were explained about the purpose, methods and effects of the clinical trial and then, signed a written consent form.
8. 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

1. Patients who have hepatitis C (HCV), hepatitis D (HDV), or human immunodeficiency virus (HIV)
2. 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
3. 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
4. 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
5. 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
6. 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)
7. 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
8. 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.
9. 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.)
10. 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
11. Pregnant women, lactating women, or patients who planned pregnancy during a trial period
12. Patients who have hypersensitivity to the clinical trial drug in this clinical trial
13. Patients who have a past medical history of clinical alcohol or drug abuse within a year before screening or now are abusers
14. 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
15. Patients who have other hepatic diseases (hematochromatosis, Wilson's disease, alcoholic liver diseases, nonalcoholic steatohepatitis, α1-antitrypsin deficiency) except hepatitis B
16. Patients who received an organ transplant
17. 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
18. Patients who are decided by an investigator as unsuitable for conducting this clinical trial
Minimum Eligible Age

20 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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IlDong Pharmaceutical Co Ltd

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kwan Sik Lee, M.d., Ph.D

Role: PRINCIPAL_INVESTIGATOR

Kangnam Severance Hospital, Yonsei University, Seoul, Korea

Young Oh Kweon, M.D., Ph.D

Role: PRINCIPAL_INVESTIGATOR

Kyungpook National University Hospital, Seoul, Korea

Hyung Joon Yim, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Korea University Medical Center, Ansan, Kyunggi-do, Korea

Soon Ho Um, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Korea University Medical Center, Seoul, Korea

Won Kim, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Boramae medical Center, Seoul, Korea

Sung Jae Park, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Inje University Busan Paik Hospital, Pusan, Korea

Yoon Jun Kim, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital, Seoul, Korea

Yoon Jun Kim, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Korea

Young-Suk Lim, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Asan Medical Center, Seoul, Korea

JinMo Yang, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

The Catholic University of Korea, Seoul St. Vincent's Hospital, Seoul, Korea

Jang, Jae Young, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Soonchunhyang University Hospital, Seoul, Korea

Jae-Youn Cheong, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Ajou University Medical Center, Suwon, Kyunggi-do, Korea

Neung Hwa Park, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Ulsan University Hospital, Ulsan, Korea

Moon Young Kim, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Wonju Sevrerance Christian Hospital, Wonju, Kangwon-do, Korea

Jin-Woo Lee, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Inha University Hospital, Incheon, Inchen, Korea

Dong Joon Kim, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Hallym University Medical Center, ChunCheon, Kangwon-do, Korea

Byung Seok Lee, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Chungnam National University Hospital

Joo Hyun Sohn, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Hanyang University Guri Hospital, Guri, Kyunggi-do, Korea

Kwang-Hyub Han, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Severance Hospital of Yonsei University, Seoul, Korea

Hong Soo Kim, M.D., Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Soonchunhyang University Hospital, Choenan, Chungchoengnam-do, Korea

Locations

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Soonchunhyang University Hospital

Cheonan, Chungchoengnam-do, South Korea

Site Status

Hallym University Medical Center

Chuncheon, Gangwon-do, South Korea

Site Status

Wonju Sevrerance Christian Hospital

Wŏnju, Gangwon-do, South Korea

Site Status

Hanyang University Guri Hospital

Guri-si, Gyeonggi-do, South Korea

Site Status

Ajou University Medical Center

Suwon, Gyeonggi-do, South Korea

Site Status

Korea University Medical Center

Ansan, Kyounggi-do, South Korea

Site Status

Kyungpook National University Hospital

Daegu, , South Korea

Site Status

Chungnam National University Hospital

Daejeon, , South Korea

Site Status

Inha University Hospital

Incheon, , South Korea

Site Status

Inje University Busan Paik Hospital

Pusan, , South Korea

Site Status

Asan Medical Center

Seoul, , South Korea

Site Status

Gangnam Severance Hospital

Seoul, , South Korea

Site Status

Korea University Medical Center

Seoul, , South Korea

Site Status

Seoul National University Boramae medical Center

Seoul, , South Korea

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Severance Hospital of Yonsei University

Seoul, , South Korea

Site Status

Soonchunhyang University Hospital

Seoul, , South Korea

Site Status

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, , South Korea

Site Status

The Catholic University of Korea, Seoul St. Vincent's Hospital

Seoul, , South Korea

Site Status

Ulsan University Hospital,

Ulsan, , South Korea

Site Status

Countries

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South Korea

References

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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.

Reference Type DERIVED
PMID: 38473248 (View on PubMed)

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.

Reference Type DERIVED
PMID: 33493393 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32355123 (View on PubMed)

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.

Reference Type DERIVED
PMID: 30448598 (View on PubMed)

Other Identifiers

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ID_BVCL011

Identifier Type: -

Identifier Source: org_study_id

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