Entecavir for Biological Agents Associated HBV Reactivation in Rheumatoid Arthritis Patients

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified July 2013 by Taipei Veterans General Hospital, Taiwan
Sponsor:
Collaborator:
Bristol-Myers Squibb
Information provided by (Responsible Party):
vghtpe user, Taipei Veterans General Hospital,Taiwan
ClinicalTrials.gov Identifier:
NCT01907230
First received: July 14, 2013
Last updated: July 18, 2013
Last verified: July 2013
  Purpose

Antiviral prophylaxis can prevent the risk of biologic agents-associated HBV reactivation in hepatitis B inactive carriers and patients with past HBV infection


Condition Intervention Phase
Rheumatoid Arthritis
Hepatitis B Reactivation
Exposure to Hepatitis B Virus
Drug: Entecavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Propylactic Use of Entecavir for Biological Agents Associated Hepatitis B Virus Reactivation in Rheumatoid Arthritis Patients: a Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Taipei Veterans General Hospital, Taiwan:

Primary Outcome Measures:
  • HBV reactivation [ Time Frame: 12 months after biologic treatment ] [ Designated as safety issue: No ]
    The main goal of the study is to delineate the incidence of HBV reactivation during and after biologic treatment in RA patients who are inactive HBV carriers or have past HBV infection, and tries to define the optimal HBV monitoring and antiviral prophylactic strategy in RA patients.


Secondary Outcome Measures:
  • HBsAg reverse seroconversion in occult HB patients. [ Time Frame: 12 months after biologic treatment ] [ Designated as safety issue: No ]

Estimated Enrollment: 220
Study Start Date: July 2013
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Entecavir, Prophylactic group
Participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment will be continued normally for 12 months (6 months after stopping biologic therapy or till restart another course of biologic treatment if the clinicians' judgment is minimal risk of reactivation after the first course of biologic agent treatment).
Drug: Entecavir
In the prophylactic group, participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment will be continued normally for 12 months (6 months after stopping biologic therapy or till restart another course of biologic treatment if the clinicians' judgment is minimal risk of reactivation after the first course of biologic agent treatment).
Other Name: Baraclude
No Intervention: Control group (pre-emptive treatment)
Patients will start entecavir therapy, 0.5 mg/day orally, when reactivation of HBV (defined as detectable HBV viral loads for 2 consecutive visits with at least one month apart), and continued entecavir treatment until undetectable HBV viral loads for 1 year (consistent with current APASL recommendation).

Detailed Description:

The risk of HBV reactivation is associated with the intensity of immunosuppression. Biological therapies block the action of biological products involved in immune-inflammatory pathogenesis of many diseases. However, these biologic agents induce a profound immunosuppression, and their use has been reported to be associated with HBV reactivation. Currently, the actual incidence of HBV reactivation in rheumatic patients who underwent biologic treatments (TNF-a blockades) is unclear, especially in rheumatoid arthritis (RA) patients with past hepatitis B infection. In this study, we plan to enroll RA patients who are inactive HBV carriers (HBsAg-positive/undetectable HBV viral loads; subgroup 1), or have past HBV infection (HBsAg-negative/anti-HBc-positive/undetectable HBV viral loads; subgroup 2); and first line biologic treatment (Humira or Enbrel) is indicated due to active rheumatoid arthritis according to Disease Activity Score of 28 joints (DAS28). Patients will be randomized in a 1:1 ratio to receive either prophylactic or therapeutic (pre-emptive) entecavir treatment for each subgroup. In the prophylactic group, participants will initiate entecavir 0.5 mg/day orally one week before biologic treatment. Entecavir treatment will be continued normally for 12 months. In the therapeutic (pre-emptive) group, patients will start entecavir therapy, 0.5 mg/day orally, when reactivation of HBV (pre-emptive treatment). HBV reactivation is defined as detectable HBV viral loads for 2 consecutive visits of one month apart. The main goal of the study is to delineate the incidence of HBV reactivation during and after biologic treatment in RA patients who are inactive HBV carriers or have past HBV infection, and tries to define the optimal HBV monitoring and antiviral prophylactic strategy in RA patients.

  Eligibility

Ages Eligible for Study:   20 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. HBsAg-positive for more than 6 months and undetectable HBV DNA (Subgroup 1)or HBsAg-negative but anti-HBc positive with undetectable HBV DNA (by Roche Cobas amplicor HBV monitor, Roche) (Subgroup 2)
  2. Rheumatoid arthritis patients who plan to treat with biological agents, including Humira or Enbrel; as first line biologic treatment is indicated due to active rheumatoid arthritis according to DAS28.

Exclusion Criteria:

  1. HCV, HIV, or HDV coinfection.
  2. HCC or other malignancy within 3 years.
  3. Decompensated liver cirrhosis (CTP score >= 7)
  4. Uremia patients under hemodialysis or continuous ambulatory peritoneal dialysis or patients with Ccr < 50 mL/min
  5. Pregnant or breastfeeding women
  6. Women of child-bearing potential (WOCBP) who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study drug
  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: NCT01907230

Contacts
Contact: Yi-Hsiang Huang, MD, Ph.D. +886-2-28712121 ext 3055 yhhuang@vghtpe.gov.tw

Locations
Taiwan
Division of Gastroenterology & Division of Allergy Immunology and Rheumatology, Taipei Veterans General Hospital Not yet recruiting
Taipei, Taiwan, 11217
Contact: Chieh-Ju Lee    +886-2-28712121 ext 2972      
Principal Investigator: Yi-Hsiang Huang, MD, Ph.D.         
Sub-Investigator: Hsiao-Yi Lin, MD         
Sponsors and Collaborators
Taipei Veterans General Hospital, Taiwan
Bristol-Myers Squibb
Investigators
Principal Investigator: Yi-Hsiang Huang, MD, Ph.D. Taipei Veterans General Hospital, Taiwan
  More Information

No publications provided

Responsible Party: vghtpe user, Professor: Yi-Hsiang Huang, Taipei Veterans General Hospital,Taiwan
ClinicalTrials.gov Identifier: NCT01907230     History of Changes
Other Study ID Numbers: AI463-962
Study First Received: July 14, 2013
Last Updated: July 18, 2013
Health Authority: Taiwan : Food and Drug Administration

Keywords provided by Taipei Veterans General Hospital, Taiwan:
Rheumatoid arthritis
Inactive HBV carrier
Resolved Hepatitis B
HBV reactivation
Anti-tumor necrotic factor-alfa

Additional relevant MeSH terms:
Hepatitis B
Arthritis
Arthritis, Rheumatoid
Hepatitis
Hepatitis A
Autoimmune Diseases
Connective Tissue Diseases
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Immune System Diseases
Joint Diseases
Liver Diseases
Musculoskeletal Diseases
Picornaviridae Infections
Rheumatic Diseases
RNA Virus Infections
Virus Diseases
Entecavir
Anti-Infective Agents
Antiviral Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014