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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

September 24, 2012
April 18, 2013
September 2012
August 2015   (final data collection date for primary outcome measure)
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)
Same as current
Complete list of historical versions of study NCT01694264 on ClinicalTrials.gov Archive Site
Incidence of HBV reactivation among different anti-TNFα treatment groups [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Study of Anti-Viral Prophylaxis for HBsAg(+) or HBcAb(+)/HBsAb(-) Patients Starting Anti-TNFα
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

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

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.

Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
  • Chronic Hepatitis B
  • Rheumatoid Arthritis
  • Ankylosing Spondylitis
  • Psoriatic Arthritis
  • Juvenile Idiopathic Arthritis
  • 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
  • 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
  • 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.
    Intervention: Drug: Entecavir
  • 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.
    Intervention: Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
128
August 2015
August 2015   (final data collection date for primary outcome measure)

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
Both
16 Years to 85 Years
No
Contact: Kichul Shin, MD, PhD 82-2-870-3198 kideb1@snu.ac.kr
Korea, Republic of
 
NCT01694264
H-1112-073-390
No
Seoul National University Hospital
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
Principal Investigator: Yeong wook Song, MD, PhD Division of Rheumatology, Seoul National University Hospital
Seoul National University Hospital
April 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP