Clinical trial NCT00313274: Safety and Antiviral Activity Study of Clevudine 30 mg QD in Patients With HBeAg(-) Chronic HBV
Official title: A Double-Blind, Randomized, Parallel, Placebo-Controlled Phase III Study to Evaluate the Safety and Antiviral Activity of Clevudine (L-FMAU) 30 mg QD in Patients With HBeAg Negative Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hepatitis B
Lead sponsor: Bukwang Pharmaceutical
Sponsor class: INDUSTRY
First posted: 2006-04-12
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine safety and efficacy of 30mg daily dose of clevudine (L-FMAU) at 24 weeks of treatment in chronic HBV infected patients with HBeAg negative


Eligibility criteria: Inclusion Criteria:

1. Patients who were between 18 and 60, inclusive
2. Patients with HBV DNA levels 1 x 105 copies/mL within 30 days of baseline.
3. Patients who were documented to be HBsAg positive for \> 6 months (documentation of positive HBsAg for the previous 6 months included previous laboratory reports showing HBsAg positive at least 6 month ago OR lab results showing IgM anti-HBc negative and IgG anti-HBc positive at screening).
4. Patients who were HBeAg negative and HBeAb positive.
5. Patients with ALT levels which were in the range of ≥1.2 and \< 15 times the upper limit of normal (ULN) and bilirubin levels less than 2.0 mg/dL, prothrombin time of less than 1.7 (INR), a serum albumin level of at least 3.5 g/dL.
6. Women of childbearing potential with a negative serum (β-HCG) pregnancy test taken within 14 days of starting therapy.
7. Patients who were able to give written informed consent prior to study start and to comply with the study requirements.

Exclusion Criteria:

1. Patients who were currently receiving antiviral, immunomodulatory or corticosteroid therapy.
2. Patients previously treated with lamivudine, lobucavir, famciclovir, adefovir or any other investigational nucleoside for HBV infection. Previous treatment with interferon that had ended less than 6 months prior to the screening visit.
3. Patients with a history of ascites, variceal hemorrhage or hepatic encephalopathy.
4. Patients coinfected with HCV, HDV or HIV.
5. Patients with clinical evidence of liver mass or with alfa-fetoprotein \> 50 ng/mL
6. Patients who were pregnant or breast-feeding.
7. Patients who were unwilling to use an "effective" method of contraception during the treatment period and for up to 3 months after cessation of therapy. For males, condoms should be used. Females had to be surgically sterile (via hysterectomy or bilateral tubal ligation) or post-menopausal or using at least medically acceptable barrier method of contraception (i.e. IUD, barrier methods with spermicide or abstinence)
8. Patients with a clinically relevant history of abuse of alcohol or drugs.
9. Patients with a significant gastrointestinal, renal, hepatic (decompensated), broncho-pulmonary, biliary diseases except asymptomatic GB stone, neurological, cardiovascular, oncologic or allergic disease. The patient with a benign tumor was excluded if judged by an investigator that the continuation of study would be interfered by benign tumor.
10. Patients with creatinine clearance less than 60mL/min as estimated by the following formula:

(140-age in years) (body weight \[kg\])/(72) (serum creatinine \[mg/dL\]) \[Note: multiply estimates by 0.85 for women\]

Primary outcomes:
measure: Efficacy:
measure: Antiviral activity (change from baseline in HBV DNA (log 10))
measure: Safety:
measure: Laboratory tests
measure: Adverse Events
measure: Vital signs
measure: ECG
Secondary outcomes:
measure: Efficacy
measure: Antiviral activity: proportion of patients with HBV DNA below the assay limit of detection (<4,700 copies/mL by Digene Hybrid Capture II assay)
measure: Biochemical improvement (e.g. ALT normalization )
Other outcomes:
Locations:
city: Bupyoung-dong
country: Korea, Republic of
facility: St. Mercy's Hospital
state: Bupyoung-gu, Incheon
city: Pyoung-dong
country: Korea, Republic of
facility: Kangbuk Samsung Hospital
state: Chongro-gu, Seoul
city: Jung-gu
country: Korea, Republic of
facility: Keimyumg University Dongsan Medical Center
state: Daegu
city: Hak-1-dong
country: Korea, Republic of
facility: Chonnam National University Hospital
state: Dong-gu, Gwangju-si
city: Seoul City
country: Korea, Republic of
facility: Korea University Guro Hospital
state: Guro-gu
city: Iksan-City
country: Korea, Republic of
facility: Wonkwang University Hospital
state: Jeonbuk
city: Jeonju-city
country: Korea, Republic of
facility: Chonbuk National University Hospital
state: Jeonbuk
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
state: Jongno-Gu
city: Sinhung-dong
country: Korea, Republic of
facility: Inha University Hospital
state: Jung-gu, Incheon
city: Dogok-dong
country: Korea, Republic of
facility: Yongdong Severance Hospital
state: Kangnam-gu, Seoul
city: Pungnap-dong
country: Korea, Republic of
facility: Seoul Asan Medical Center
state: Kangnam-gu, Seoul
city: Ilsan-gu
country: Korea, Republic of
facility: National Cancer Center
state: Kyounggi-do
city: Puch'onae
country: Korea, Republic of
facility: St. Holly Family Mary's Hospital
state: Kyounggi-do
city: Seongnam-gu
country: Korea, Republic of
facility: Pochon CHA University Hospital
state: Kyounggi-do
city: Dae myoung-dong
country: Korea, Republic of
facility: Yeungnam University Medical Center
state: Nam-gu, Taegu
city: Incheon
country: Korea, Republic of
facility: Gil Medical Center
state: Namdong-Gu
city: Hagye 1-dong
country: Korea, Republic of
facility: Nowon Eulji Hospital
state: Nowon-gu, Seoul
city: Ji-dong
country: Korea, Republic of
facility: St. Vincent's Hospital
state: Paldal-gu, Suwon
city: Gaegeum-dong
country: Korea, Republic of
facility: Pusan Paik Hospital
state: Pusan
city: Ami-dong
country: Korea, Republic of
facility: Pusan National University Hospital
state: Seo-gu, Pusan
city: Amnam-dong
country: Korea, Republic of
facility: Kosin Medical Center
state: Seo-gu, Pusan
city: Banpo-dong
country: Korea, Republic of
facility: KangNam St. Mary's Hospital
state: Seocho-gu, Seoul
city: Shinchon- dong
country: Korea, Republic of
facility: Severance Hospital
state: Seodaemun-gu, Seoul
city: Jeo-dong
country: Korea, Republic of
facility: Seoul Paik Hospital
state: Seoul
city: Ilwon-dong
country: Korea, Republic of
facility: Samsung Medical Center
state: Songpa-gu, Seoul
city: Anam-dong
country: Korea, Republic of
facility: Korea University Anam Hospital
state: Sungbuk-ku, Seoul
city: Mokdong
country: Korea, Republic of
facility: Ehwa Womans University Mokdong Hospital
state: Yangcheon-gu, Seoul
city: Daelim-dong
country: Korea, Republic of
facility: Kangnam Sacred Heart Hospital
state: Yongdeungpo-gu, Seoul
city: Hannam-dong
country: Korea, Republic of
facility: Soon Chun Hyang University Hospital
state: Yongsan-gu, Seoul
city: Seoul
country: Korea, Republic of
facility: St. Mary's Hospital
state: Yungdungpo-Gu
Study officials:
affiliation: Seoul National University Hospital
name: Hyo-Suk Lee, MD. PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yoo BC, Kim JH, Kim TH, Koh KC, Um SH, Kim YS, Lee KS, Han BH, Chon CY, Han JY, Ryu SH, Kim HC, Byun KS, Hwang SG, Kim BI, Cho M, Yoo K, Lee HJ, Hwang JS, Kim YS, Lee YS, Choi SK, Lee YJ, Yang JM, Park JW, Lee MS, Kim DG, Chung YH, Cho SH, Choi JY, Kweon YO, Lee HY, Jeong SH, Yoo HW, Lee HS. Clevudine is highly efficacious in hepatitis B e antigen-negative chronic hepatitis B with durable off-therapy viral suppression. Hepatology. 2007 Oct;46(4):1041-8. doi: 10.1002/hep.21800.