Phase 3 Study of Besifovir

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by IlDong Pharmaceutical Co Ltd
Sponsor:
Information provided by (Responsible Party):
IlDong Pharmaceutical Co Ltd
ClinicalTrials.gov Identifier:
NCT01937806
First received: September 4, 2013
Last updated: March 12, 2014
Last verified: March 2014
  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


Condition Intervention Phase
Chronic Hepatitis B
Drug: besifovir 150mg
Drug: tenofovir 300mg
Phase 3

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:


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:

  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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01937806

Contacts
Contact: Se-Eun Kim, Master 82(0)2 526 3518 trpv1@ildong.com
Contact: gayou Hong, Bechelor 82(0)2 526 3519 gyhong@ildong.com

Locations
Korea, Republic of
Soonchunhyang University Hospital 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 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 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 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 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 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 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 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 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 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 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 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 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 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 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 Recruiting
Seoul, Korea, Republic of
Contact: Won Kim, M.D., Ph.D.         
Principal Investigator: Won Kim, M.D., Ph.D.         
Korea University Medical Center 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, Recruiting
Ulsan, Korea, Republic of
Contact: Neung Hwa Park, M.D., Ph.D.         
Principal Investigator: Neung Hwa Park, M.D., Ph.D.         
Sponsors and Collaborators
IlDong Pharmaceutical Co Ltd
Investigators
Principal Investigator: Kwan Sik Lee, M.d., Ph.D Kangnam Severance Hospital, Yonsei University, Seoul, Korea, Republic of
Principal Investigator: Young Oh Kweon, M.D., Ph.D Kyungpook National University Hospital, Seoul, Korea, Republic of
Principal Investigator: Hyung Joon Yim, M.D., Ph.D. Korea University Medical Center, Ansan, Kyunggi-do, Korea, Republic of
Principal Investigator: Soon Ho Um, M.D., Ph.D. Korea University Medical Center, Seoul, Korea, Republic of
Principal Investigator: Won Kim, M.D., Ph.D. Seoul National University Boramae medical Center, Seoul, Korea, Republic of
Principal Investigator: Sung Jae Park, M.D., Ph.D. Inje University Busan Paik Hospital, Pusan, Korea, Republic of
Principal Investigator: Yoon Jun Kim, M.D., Ph.D. Seoul National University Hospital, Seoul, Korea, Republic of
Principal Investigator: Yoon Jun Kim, M.D., Ph.D. The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Korea, Republic of
Principal Investigator: Young-Suk Lim, M.D., Ph.D. Asan Medical Center, Seoul, Korea, Republic of
Principal Investigator: JinMo Yang, M.D., Ph.D. The Catholic University of Korea, Seoul St. Vincent's Hospital, Seoul, Korea, Republic of
Principal Investigator: Jang, Jae Young, M.D., Ph.D. Soonchunhyang University Hospital, Seoul, Korea, Republic of
Principal Investigator: Jae-Youn Cheong, M.D., Ph.D. Ajou University Medical Center, Suwon, Kyunggi-do, Korea, Republic of
Principal Investigator: Neung Hwa Park, M.D., Ph.D. Ulsan University Hospital, Ulsan, Korea, Republic of
Principal Investigator: Moon Young Kim, M.D., Ph.D. Wonju Sevrerance Christian Hospital, Wonju, Kangwon-do, Republic of
Principal Investigator: Jin-Woo Lee, M.D., Ph.D. Inha University Hospital, Incheon, Inchen, Korea, Republic of
Principal Investigator: Dong Joon Kim, M.D., Ph.D. Hallym University Medical Center, ChunCheon, Kangwon-do, Korea, Republic of
Principal Investigator: Byung Seok Lee, M.D., Ph.D. Chungnam National University Hospital, Daejeon, Korea, Republic of
Principal Investigator: Joo Hyun Sohn, M.D., Ph.D. Hanyang University Guri Hospital, Guri, Kyunggi-do, Korea, Republic of
Principal Investigator: Kwang-Hyub Han, M.D., Ph.D. Severance Hospital of Yonsei University, Seoul, Korea, Republic of
Principal Investigator: Hong Soo Kim, M.D., Ph.D. Soonchunhyang University Hospital, Choenan, Chungchoengnam-do, Korea, Republic of
  More Information

No publications provided

Responsible Party: IlDong Pharmaceutical Co Ltd
ClinicalTrials.gov Identifier: NCT01937806     History of Changes
Other Study ID Numbers: ID_BVCL011
Study First Received: September 4, 2013
Last Updated: March 12, 2014
Health Authority: Korea, Republic of : Ministry of Food and Drug Safety

Keywords provided by IlDong Pharmaceutical Co Ltd:
Chronic hepatitis B

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Tenofovir disoproxil
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 27, 2014