Phase 3 and Extensional Study of Besifovir

NCT01937806 | Unknown Phase 3

• 1 other identifier: ID_BVCL011
• Study Type: interventional
• Target: 197
• Locations: 1 country
• Sites: 20

Brief Summary

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

Conditions

Chronic Hepatitis B

Keywords

Chronic hepatitis B

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (10)

• 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

  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

  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

Study Arms (2)

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.

Drug: besifovir 150mg

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.

Drug: tenofovir 300mg

Interventions

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.

besifovir 150mg

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.

Tenofovir 300mg

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.).

You may not qualify if:

• 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.)

Sponsors & Collaborators

• IlDong Pharmaceutical Co Ltd: lead

Study Sites (20)

Soonchunhyang University Hospital

Cheonan, Chungchoengnam-do, South Korea

Location

Hallym University Medical Center

Chuncheon, Gangwon-do, South Korea

Location

Wonju Sevrerance Christian Hospital

Wŏnju, Gangwon-do, South Korea

Location

Hanyang University Guri Hospital

Guri-si, Gyeonggi-do, South Korea

Location

Ajou University Medical Center

Suwon, Gyeonggi-do, South Korea

Location

Korea University Medical Center

Ansan, Kyounggi-do, South Korea

Location

Kyungpook National University Hospital

Daegu, South Korea

Location

Chungnam National University Hospital

Daejeon, South Korea

Location

Inha University Hospital

Incheon, South Korea

Location

Inje University Busan Paik Hospital

Pusan, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Gangnam Severance Hospital

Seoul, South Korea

Location

Korea University Medical Center

Seoul, South Korea

Location

Seoul National University Boramae medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital of Yonsei University

Seoul, South Korea

Location

Soonchunhyang University Hospital

Seoul, South Korea

Location

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

Seoul, South Korea

Location

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

Seoul, South Korea

Location

Ulsan University Hospital,

Ulsan, South Korea

Location

Related Publications (4)

• 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.

  PMID: 38473248 DERIVED

• 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.

  PMID: 33493393 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.

  PMID: 32355123 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.

  PMID: 30448598 DERIVED

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

((1-((2-amino-9H-purin-9-yl)methyl)cyclopropyl)oxy)methylphosphonic acid dipivoxyl; Tenofovir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• 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.

  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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2013
• First Posted: September 10, 2013
• Study Start: October 1, 2013
• Primary Completion: February 1, 2016
• Study Completion: January 1, 2023
• Last Updated: January 27, 2020

Record last verified: 2020-01

Locations

KR (20)