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

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Seoul National University Hospital
Sponsor:
Collaborators:
Konkuk University Medical Center
Kyungpook National University
Kyunghee University Medical Center
Kyung Hee University Gangdong Hospital
Gachon University Gil Medical Center
Daegu Catholic University Medical Center
Eulji University Hospital
SMG-SNU Boramae Medical Center
The Catholic University of Korea
Severance Hospital
Ajou University School of Medicine
Ewha Womans University
Inha University Hospital
Chonnam National University Hospital
Chonbuk National University Hospital
Chungnam National University Hospital
Hallym University Medical Center
Hanyang University
Dong-A University
Korea University Guro Hospital
Information provided by (Responsible Party):
Seoul National University Hospital
ClinicalTrials.gov Identifier:
NCT01694264
First received: September 24, 2012
Last updated: April 18, 2013
Last verified: April 2013
  Purpose

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


Condition Intervention Phase
Chronic Hepatitis B
Rheumatoid Arthritis
Ankylosing Spondylitis
Psoriatic Arthritis
Juvenile Idiopathic Arthritis
Drug: Entecavir
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Randomized, Double-blinded, Phase 3, Multicenter, Investigator-initiated Trial for Entecavir for Prophylaxis of Hepatitis B Virus (HBV) Reactivation in HBV Surface Antigen or Anti-HBc Positive Patients Undergoing Anti-TNFα Treatment

Resource links provided by NLM:


Further study details as provided by Seoul National University Hospital:

Primary Outcome Measures:
  • The frequency (events) of HBV reactivation [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
    1. Elevated HBV DNA titer: ≥1 log10 rise in HBV DNA level compared with baseline level (virologic breakthrough), along with
    2. Increase of AST or ALT above 32 x upper limit of normal (ULN) (biochemical breakthrough)


Secondary Outcome Measures:
  • Incidence of HBV reactivation among different anti-TNFα treatment groups [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 128
Study Start Date: September 2012
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: 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.
Other Name: Baraclude (Bristol-Myers Squibb) 0.5mg
Placebo Comparator: 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.
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.
Other Name: placebo, prepared by Bristol-Myers Squibb

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.

  Eligibility

Ages Eligible for Study:   16 Years to 85 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT01694264

Contacts
Contact: Kichul Shin, MD, PhD 82-2-870-3198 kideb1@snu.ac.kr

Locations
Korea, Republic of
Hallym University Sacred Heart Hospital Recruiting
Anyang, Korea, Republic of
Dong-A University, College of Medicine Recruiting
Busan, Korea, Republic of
Daegu Catholic Medical Center Recruiting
Daegu, Korea, Republic of
Kyungpook National University Hospital Recruiting
Daegu, Korea, Republic of
Chungnam National University Hospital Recruiting
Daejun, Korea, Republic of
Daejun Eulji University Hospital Recruiting
Daejun, Korea, Republic of
Chonnam National University Hospital Recruiting
Gwangju, Korea, Republic of
Gachon University Gil Medical Center Recruiting
Incheon, Korea, Republic of
Inha University Hospital Recruiting
Incheon, Korea, Republic of
Chonbuk National University Hospital Recruiting
Jeonju, Korea, Republic of
Kyung Hee University Gangdong Hospital Recruiting
Seoul, Korea, Republic of
SMG-SNU Boramae Medical Center Recruiting
Seoul, Korea, Republic of
Ewha Womans University Mokdong Hospital Recruiting
Seoul, Korea, Republic of
Konkuk University Hospital Recruiting
Seoul, Korea, Republic of
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of, 110-744
Principal Investigator: Yeong Wook Song, MD, PhD         
Kyunghee University Medical Center Recruiting
Seoul, Korea, Republic of
The Catholic University of Korea, Seoul St. Mary's Recruiting
Seoul, Korea, Republic of
Hanyang University Hospital Recruiting
Seoul, Korea, Republic of
Severance Hospital Recruiting
Seoul, Korea, Republic of
The Catholic University of Korea, Yeouido St. Mary's Hospital Recruiting
Seoul, Korea, Republic of
Korea University Guro Hospital Recruiting
Seoul, Korea, Republic of
Ajou University Hospital Recruiting
Suwon, Korea, Republic of
Sponsors and Collaborators
Seoul National University Hospital
Konkuk University Medical Center
Kyungpook National University
Kyunghee University Medical Center
Kyung Hee University Gangdong Hospital
Gachon University Gil Medical Center
Daegu Catholic University Medical Center
Eulji University Hospital
SMG-SNU Boramae Medical Center
The Catholic University of Korea
Severance Hospital
Ajou University School of Medicine
Ewha Womans University
Inha University Hospital
Chonnam National University Hospital
Chonbuk National University Hospital
Chungnam National University Hospital
Hallym University Medical Center
Hanyang University
Dong-A University
Korea University Guro Hospital
Investigators
Principal Investigator: Yeong wook Song, MD, PhD Division of Rheumatology, Seoul National University Hospital
  More Information

No publications provided

Responsible Party: Seoul National University Hospital
ClinicalTrials.gov Identifier: NCT01694264     History of Changes
Other Study ID Numbers: H-1112-073-390
Study First Received: September 24, 2012
Last Updated: April 18, 2013
Health Authority: Korea: Food and Drug Administration

Keywords provided by Seoul National University Hospital:
HBV surface antigen
Anti-HBc positive
Anti-TNFα Treatment
Reactivation

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Arthritis
Arthritis, Rheumatoid
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Spondylitis
Spondylitis, Ankylosing
Arthritis, Psoriatic
Arthritis, Juvenile
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Hepadnaviridae Infections
DNA Virus Infections
Bone Diseases, Infectious
Infection
Bone Diseases
Spinal Diseases

ClinicalTrials.gov processed this record on September 15, 2014