Study of Anti-Viral Prophylaxis for HBsAg(+) or HBcAb(+)/HBsAb(-) Patients Starting Anti-TNFα

NCT ID: NCT01694264

Last Updated: 2017-03-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-09-01
• Study Completion Date: 2015-12-31

Brief Summary

Analysis of effect of anti-TNFα treatment on HBV reactivation among patients with systemic rheumatic disease, especially rheumatoid arthritis

Detailed Description

Biologic agents, especially anti-TNFα treatments are widely used in inflammatory arthritis such as rheumatoid arthritis (RA) and ankylosing spondylitis (AS). More than 60% of RA or AS patients achieve good clinical response to anti-TNFα treatment. However, TNFα is also an important mediator participating in the normal immune response to infectious agents, in particular intracellular microorganisms in the human body. Therefore, opportunistic infections such as tuberculosis, viral and fungal infections have been of concern when using anti-TNFα agents. With accumulating experience, the treatment guideline for anti-TNFα therapy in latent tuberculosis is now well established. It is noteworthy that there are a number of case reports describing hepatitis B virus (HBV) reactivation in otherwise asymptomatic carriers who received anti-TNFα treatment. Anti-TNFα agents are now utilized as a promising treatment regimen for RA and AS treatment for even HBsAg carriers, yet there are still concerns of the risk of anti-TNFα therapy contributing to HBV reactivation. In our previous studies, we found that anti-viral therapy before starting anti-TNFα treatment may reduce the incidence of HBV reactivation, and that entecavir is likely more suitable in long-term prophylaxis for HBsAg carriers under anti-TNFα treatment. This justifies the need of a prospective trial that could demonstrate the long-term effects of prophylaxis in using anti-TNFα therapy in this subgroup of patients. It would help clinicians understand 1) whether anti-viral therapy is necessary in inactive HBsAg carriers initiating anti-TNFα treatment, and 2) at what time point would we most likely witness HBV reactivation after starting anti-TNFα therapy without anti-viral therapy coverage. In addition to established nationwide network of Rheumatologists working in major academic institutes in Korea, our division in Seoul National University Hospital has led many multi-center trials throughout the past years. In summary, the question of whether to combine anti-viral prophylaxis in HBsAg carriers starting anti-TNFα therapy is an important issue to Rheumatologists. There is no guideline for managing this subset of patients, and clinicians normally begin anti-viral therapy after the patient's liver function worsens. Therefore, our nationwide network of specialists proposes to launch a prospective study to investigate the benefit of anti-viral prophylaxis with entecavir in HBsAg carriers starting anti-TNFα treatment.

Conditions

Chronic Hepatitis B; Rheumatoid Arthritis; Ankylosing Spondylitis; Psoriatic Arthritis; Juvenile Idiopathic Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Experimental Group

Entecavir (Baraclude (Bristol-Myers Squibb) 0.5mg.) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered.

Group Type: EXPERIMENTAL

Entecavir

Intervention Type: DRUG

Entecavir (Baraclude (Bristol-Myers Squibb) 0.5mg.) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered.

Control Group

Placebo of Entecavir (prepared by Bristol-Myers Squibb) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo of Entecavir (prepared by Bristol-Myers Squibb) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered.

Interventions

Entecavir

Entecavir (Baraclude (Bristol-Myers Squibb) 0.5mg.) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered.

Intervention Type: DRUG

Placebo

Placebo of Entecavir (prepared by Bristol-Myers Squibb) will be taken orally on an empty stomach (2 hours after a meal or at least 2 hours before the next meal), once daily from 1 week before starting anti-TNFα and continue 72 weeks after anti-TNFα is administered.

Intervention Type: DRUG

Other Intervention Names

Baraclude (Bristol-Myers Squibb) 0.5mg; placebo, prepared by Bristol-Myers Squibb

Eligibility Criteria

Inclusion Criteria

• Chronic hepatitis B, inactive HBsAg carriers or anti-HBc antibody positive patients with AST, ALT level equal or lower than 2x ULN
• Patient who has systemic rheumatic disease for which anti-TNFα treatment indication has been approved by the KFDA; rheumatoid arthritis (RA, 1987 ACR criteria), ankylosing spondylitis (AS, modified New York criteria), psoriatic arthritis (PsA, modified ESSG criteria), and juvenile rheumatoid arthritis (JRA, 1977 ACR criteria).
• Patient who is eligible to start anti-TNFα treatment (etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol) due to treatment failure of other DMARDs against underlying RA, AS, PsA, or JRA. Patient who also fully understands that anti-TNFα agent expenses are not covered in this study.
• Patient who is willing and able to comply with the study drug regimen and all other study requirements
• Patient who is willing and able to provide a written informed consent to participate in the study

Exclusion Criteria

• Patient who has liver cirrhosis or a history of hepatocellular carcinoma (HCC) or findings suggestive of HCC, such as suspicious foci or elevated serum alpha fetoprotein (AFP)
• Patient who received interferon or other immunomodulatory treatment for HBV infection in the 12 months before screening for this study
• Patient who has concomitant other chronic viral infection (HCV or HIV)
• Patient who is pregnant or breastfeeding or willing to be pregnant
• A history of chronic infection, recent serious or life-threatening infection. Especially,

• Patient with current clinical or laboratory evidence of active tuberculosis (TB) or latent TB unless there is documentation of prior anti-TB treatment was appropriate in duration according to the Korea Food and Drug Administration (KFDA) guidelines for management of latent TB in patients being treated with biologic agents
• Patient with a history of herpes zoster within 2 months before screening for this study
• Active malignancy or a history of treated malignancy less than 5 years prior to screening
• Patients who are not cooperative or unable to comply with the study procedures
• Patients with any other condition which the investigator's judgment would make the patient unsuitable for inclusion in the study such as alcohol and drug abuse

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Konkuk University Medical Center

OTHER

Sponsor Role: collaborator

Kyungpook National University Hospital

OTHER

Sponsor Role: collaborator

Kyunghee University Medical Center

OTHER

Sponsor Role: collaborator

Kyung Hee University Hospital at Gangdong

OTHER

Sponsor Role: collaborator

Gachon University Gil Medical Center

OTHER

Sponsor Role: collaborator

Daegu Catholic University Medical Center

OTHER

Sponsor Role: collaborator

Eulji University Hospital

OTHER

Sponsor Role: collaborator

SMG-SNU Boramae Medical Center

OTHER

Sponsor Role: collaborator

The Catholic University of Korea

OTHER

Sponsor Role: collaborator

Severance Hospital

OTHER

Sponsor Role: collaborator

Ajou University School of Medicine

OTHER

Sponsor Role: collaborator

Ewha Womans University Mokdong Hospital

OTHER

Sponsor Role: collaborator

Inha University Hospital

OTHER

Sponsor Role: collaborator

Chonnam National University Hospital

OTHER

Sponsor Role: collaborator

Chonbuk National University Hospital

OTHER

Sponsor Role: collaborator

Chungnam National University Hospital

OTHER

Sponsor Role: collaborator

Hallym University Medical Center

OTHER

Sponsor Role: collaborator

Hanyang University

OTHER

Sponsor Role: collaborator

Dong-A University

OTHER

Sponsor Role: collaborator

Korea University Guro Hospital

OTHER

Sponsor Role: collaborator

Seoul National University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Yeong-Wook Song

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Yeong wook Song, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Division of Rheumatology, Seoul National University Hospital

Locations

Hallym University Sacred Heart Hospital

Anyang, , South Korea

Dong-A University, College of Medicine

Busan, , South Korea

Daegu Catholic Medical Center

Daegu, , South Korea

Kyungpook National University Hospital

Daegu, , South Korea

Chungnam National University Hospital

Daejun, , South Korea

Daejun Eulji University Hospital

Daejun, , South Korea

Chonnam National University Hospital

Gwangju, , South Korea

Gachon University Gil Medical Center

Incheon, , South Korea

Inha University Hospital

Incheon, , South Korea

Chonbuk National University Hospital

Jeonju, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Ewha Womans University Mokdong Hospital

Seoul, , South Korea

Hanyang University Hospital

Seoul, , South Korea

Konkuk University Hospital

Seoul, , South Korea

Korea University Guro Hospital

Seoul, , South Korea

Kyung Hee University Gangdong Hospital

Seoul, , South Korea

Kyunghee University Medical Center

Seoul, , South Korea

Severance Hospital

Seoul, , South Korea

SMG-SNU Boramae Medical Center

Seoul, , South Korea

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

Seoul, , South Korea

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

Seoul, , South Korea

Ajou University Hospital

Suwon, , South Korea

Countries

South Korea

Other Identifiers

H-1112-073-390

Identifier Type: -

Identifier Source: org_study_id