Abatacept vs Placebo in RA Patients With Hepatitis B on Entecavir Background (RA)
The purpose of this study is to investigate whether the combination of abatacept along with entecavir (the study drugs) is safe and effective in treating symptoms related to rheumatoid arthritis (RA).
Abatacept, given in an intravenous (IV - injected into a vein) as well as subcutaneous form, is approved by the FDA for the treatment of RA. In this research, abatacept will be given by injection. A subcutaneous injection is an injection given under the skin.
Entecavir, to be taken by mouth, is approved by the FDA for the treatment of hepatitis B.
The study is divided into the following time periods:
Screening Phase: Up to 4 weeks Randomized Double-blind Phase: 24 weeks Open-label Extension Phase: 24 weeksFollow-up Phase: a phone call after Week 48
Each phase contains one or more study visits.
|Study Design:||Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double Blind (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||Pilot Study to Evaluate Subcutaneous Abatacept vs Placebo in RA Patients With Hepatitis B on Entecavir Background- a Pilot, Double-blind, Placebo-controlled, Randomized, Controlled Trial.|
- Number of Participants with Serious Adverse Events [ Time Frame: Every 4 weeks from Week 4 to Week 48 ]Adverse events will be assessed at timepoints specified in the protocol.
- Number of Subjects with Hepatitis B Reactivation [ Time Frame: Every 4 Weeks from Week 4 to Week 48 ]Blood test for Hepatitis B Virus (HBV) DNA will be used.
- DAS28-ESR-4 Unit [ Time Frame: Screening, Weeks 4, 8, 12, 24, 36, and 48 ]
- CDAI Unit [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- TJC Count [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- SJC Count [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- Patient Global (Visual Analogue Scale) [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- MD Global (Visual Analogue Scale) [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- Pain (measured on a 5 point Likert scale) [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- Global Assessment of Disease Activity (as measured on a 5 point Likert scale) [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- HAQ-DI Units [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- Fatigue (as assessed by FACIT-Fatigue Unit) [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- Sleep as assessed by Medical Outcomes Study Sleep Instrument Unit [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
- ACR 20/50/70 Percentage [ Time Frame: Screening, Weeks 4,8,12,24,36,48 ]
|Study Start Date:||July 2014|
|Estimated Study Completion Date:||December 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Active Comparator: Abatacept Arm
This arm of study subjects will receive 125 mg subcutaneous abatacept during the 24 week double blind period.
Abatacept Injection, 125 mg/Syringe (125 mg/mL), is a sterile solution for SC administration, which contains approximately 126 mg abatacept.
Other Name: Orencia
Placebo Comparator: Placebo Arm
This arm of study patients will receive matching placebo injections during the 24 week double blind period.
Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder affecting 1% of the world's population. If not adequately controlled, it may lead to disability in up to 30% of patients within the first three years of disease onset  and can be associated with premature death. Recent research has suggested that the first event in the pathogenesis of RA is an antigen dependent activation of T-cells in an immunogenetically susceptible host. T-cells require two signals for activation, one involving the trimolecular complex (class II Major Histocompatibility Complex (MHC), antigen, T-cell receptor), and the other being co-stimulation of the CD28 (Cluster of Differentiation 28) molecule on T-cells by the B7 molecules (CD80 and CD86) on antigen presenting cells.
Hepatitis B virus (HBV) can cause chronic disease in 5% of immunocompetent adults and has a prevalence of over 350 million worldwide. It is a leading cause of chronic hepatitis, cirrhosis and hepatocellular cancer and accounts for one million deaths annually. In patients with chronic hepatitis B and RA, treatment options are limited. Traditional disease modifying anti-rheumatic drugs (DMARDs) are associated with hepatotoxicity and are contraindicated in chronic hepatitis. A recent retrospective analysis suggests that successful use of anti-tumor necrosis factor alpha (anti-TNF) agents may be possible in these patients but the authors do warn that these patients should be closely monitored and that fatal reactivation of hepatitis B is possible. Treatment with rituximab, a chimeric monoclonal antibody against B-cell protein CD20, is another option; however, the use of this medication in RA patients with chronic hepatitis B may also cause reactivation.
When RA patients with chronic hepatitis B were started on a Tumor Necrosis Factor (TNF) inhibitor or methotrexate (MTX), 2 of 5 HBsAg+ patients reactivated their hepatitis B, indicating a possible high rate of activation in these patients when not on hepatitis B treatment. Reactivation in this and another study occurred after 9-19 months of antirheumatic therapy. In RA patients with chronic Hepatitis B, entecavir appears to be effective at preventing reactivation.
There are no studies on the safety of abatacept in patients with RA and HBV. Adequate T-cell function is important to help cure or contain HBV infection. Our site has conducted a retrospective study that shows preliminary safety of abatacept in patients with RA and chronic Hepatitis B on antiviral therapy. The purpose of this study is to assess the safety and efficacy of abatacept in RA patients with chronic Hepatitis B in a pilot study in a randomized, controlled fashion.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02053727
|Contact: Bal-lan Yenfirstname.lastname@example.org|
|Contact: Gabriel Valdiviaemail@example.com|
|United States, California|
|Division of Rheumatology, UCLA David Geffen School of Medicine||Recruiting|
|Los Angeles, California, United States, 90095|
|Principal Investigator: Daniel E Furst, M.D.|
|Principal Investigator:||Suzanne Kafaja, M.D.||University of California, Los Angeles|