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Chronic Hepatitis BPhase 3NCT01937806

Phase 3 and Extensional Study of Besifovir

A Phase 3 study testing besifovir 150mg and tenofovir 300mg in people with Chronic Hepatitis B, run by IlDong Pharmaceutical Co Ltd at 20 sites in South Korea.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 20 years and older
Conditions the study is for
Chronic Hepatitis B
What is being tested?
besifovir 150mg and tenofovir 300mg
Could I receive a placebo?
No, everyone receives an active treatment
How many people
197 participants
Where
20 sitesSouth Korea
Study dates
Oct 2013to Jan 2023
Phase
Phase 3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 20 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.).

Who cannot join

  • 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
Show all 31Show fewer
  • 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

Trial locations and contacts

20 sites in 1 country.

20 sites in 1 country

South Korea20 sites

  • Korea University Medical Center

    Ansan, Kyounggi-do

  • Soonchunhyang University Hospital

    Cheonan, Chungchoengnam-do

  • Hallym University Medical Center

    Chuncheon, Gangwon-do

  • Kyungpook National University Hospital

    Daegu

  • Chungnam National University Hospital

    Daejeon

  • Hanyang University Guri Hospital

    Guri-si, Gyeonggi-do

  • Inha University Hospital

    Incheon

  • Inje University Busan Paik Hospital

    Pusan

  • Asan Medical Center

    Seoul

  • Gangnam Severance Hospital

    Seoul

  • Korea University Medical Center

    Seoul

  • Seoul National University Boramae medical Center

    Seoul

  • Seoul National University Hospital

    Seoul

  • Severance Hospital of Yonsei University

    Seoul

  • Soonchunhyang University Hospital

    Seoul

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

    Seoul

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

    Seoul

  • Ajou University Medical Center

    Suwon, Gyeonggi-do

  • Ulsan University Hospital,

    Ulsan

  • Wonju Sevrerance Christian Hospital

    Wŏnju, Gangwon-do

Other trials in South Korea

About this study

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

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

Read the 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.
Being tested
besifovir 150mg, tenofovir 300mg
Keywords
Chronic hepatitis B
Medical subject headings
Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • besifovir 150mgDrug

    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 300mgDrug

    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.

Study groups in NCT01937806
Study groupRoleWhat they receive
besifovir 150mgExperimentalBesifovir 150 mg q.d. + Placebo of Tenofovir Disoproxil Fumarate 300 mg q.d. + L-carnitine (L-Carn Tab. 330 mg) 660 mg q.d.
Receives: Drug: besifovir 150mg
Tenofovir 300mgActive comparatorPlacebo 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.
Receives: Drug: tenofovir 300mg

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

    Measured: at the 48th week

Secondary outcomes (10)

  1. 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

    Measured: at the 48th week

  2. Average amount of change in an HBV DNA common logarithm value at the 48th week to a base value

    Average amount of change in an HBV DNA common logarithm value at the 48th week to a base value

    Measured: at the 48th week

  3. The rate of subjects who showed ALT normalized at the 48th week

    The rate of subjects who showed ALT normalized at the 48th week

    Measured: at the 48th week

  4. 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

    Measured: at the 48th week

  5. 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

    Measured: at the 48th week

  6. 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

    Measured: at the 48th week

  7. 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

    Measured: at the 48th week

  8. 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

    Measured: at the 48th week

  9. 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

    Measured: at the 48th week

  10. 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

    Measured: at the 48th week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Sep 2013 (estimated)
  2. Study startOct 2013
  3. Primary completionFeb 2016
  4. Study completionJan 2023 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
197 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01937806
Sponsor's protocol ID
ID_BVCL011
Status last verified
Jan 2020
First submitted
4 Sep 2013
Last updated
27 Jan 2020
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 38473248

  • 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.

    PubMed 33493393

  • 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.

    PubMed 32355123

  • 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.

    PubMed 30448598

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing besifovir 150mg and tenofovir 300mg in people with Chronic Hepatitis B, run by IlDong Pharmaceutical Co Ltd at 20 sites in South Korea.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in South Korea. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01937806, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.

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