Entecavir for Biological Agents Associated HBV Reactivation in Inflammatory Arthritis Patients

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Taipei Veterans General Hospital, Taiwan
Sponsor:
Information provided by (Responsible Party):
vghtpe user, Taipei Veterans General Hospital, Taiwan
ClinicalTrials.gov Identifier:
NCT01907230
First received: July 14, 2013
Last updated: March 31, 2016
Last verified: March 2016
  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 Inflammatory 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 Study Completion Date: December 2018
Estimated Primary Completion Date: December 2018 (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 (adjust dosage according to renal function) 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 inflammatory arthritis patients who underwent biologic treatments (TNF-α blockades) is unclear, especially in inflammatory arthritis (IA) patients with past hepatitis B infection. In this study, we plan to enroll IA patients who are inactive HBV carriers (HBsAg-positive/ HBV viral loads <2000 IU/ml; subgroup 1), or have past HBV infection (HBsAg-negative/anti-HBc-positive/ HBV viral loads < 2000 IU/ml; subgroup 2); and first line biologic treatment (Humira or Enbrel or Simponi or Orencia or Mabthera or Actemra) is indicated. Patients will be randomized in a 1:1 ratio to receive either prophylactic or therapeutic 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 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 IA patients who are inactive HBV carriers or have past HBV infection, and tries to define the optimal HBV monitoring and antiviral prophylactic strategy in IA patients.
  Eligibility

Ages Eligible for Study:   20 Years to 90 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age : from 20 to 90 y/o.
  2. HBsAg-positive for more than 6 months and HBV DNA < 2000 IU/ml (Subgroup 1)or HBsAg-negative but anti-HBc positive with HBV DNA < 2000 IU/ml (Subgroup 2).
  3. Inflammatory arthritis patients who plan to treat with biological agents, including Humira or Enbrel or Simponi or Orencia or Mabthera or Actemra; as first line biologic treatment is indicated.

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 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         
Sub-Investigator: Chang-Youh Tsai, MD         
Sub-Investigator: Wei-Sheng Chen, MD         
Sponsors and Collaborators
Taipei Veterans General Hospital, Taiwan
Investigators
Principal Investigator: Yi-Hsiang Huang, MD, Ph.D. Taipei Veterans General Hospital, Taiwan
  More Information

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: March 31, 2016
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
Hepatitis
Hepatitis A
Arthritis
Arthritis, Rheumatoid
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
Entecavir
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 21, 2016