Abatacept vs Placebo in RA Patients With Hepatitis B on Entecavir Background

• Status: Withdrawn
• Trial end date: 2018-06-12
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Suzanne Kafaja; University of California, Los Angeles
• Treatments: Abatacept; Entecavir

Criteria

Inclusion Criteria:

1. Diagnosis of RA.

2. Baseline CDAI >10 with TJC (Tender Joint Count) > 4 and SJC (Swollen Joint Count) > 2.

3. Chronic Hepatitis B as defined by a history of patients with a HBsAg positive for at least 6 months with undetectable HBV DNA; or a history of patients with negative HBsAg and positive HBcAb or HBsAb, with undetectable HBV DNA.

4. No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20 ng/mL at screening,) negative liver imaging as shown by ultrasound, computerized tomography or magnetic resonance imaging within 24 weeks of screening. Participants with AFP >20 ng/mL must be evaluated clinically with additional imaging and shown not to have HCC on CT or MRI before they can be enrolled.

5. Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent) and NSAIDs (Non-Steroidal Anti-inflammatory Drugs) are permitted if the patient is on a stable dose regimen for ≥ 2 weeks prior to and including at baseline.

6. Men and women, >= 18 years of age.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding. Sexually active fertile men not using effective birth control if their partners are WOCBP (Women of Child Bearing Potential).

2. Target Disease Exceptions

a) Rheumatic autoimmune disease other than RA; fibromyalgia or keratoconjunctivitis/xerostomia are allowed, as long as these will not confound the CLINICAL EFFICACY OUTCOMES.

3. Medical History and Concurrent Diseases

1. Subjects who are impaired, incapacitated, or incapable of completing study-related assessments.

2. Subjects who underwent previous MCP (metacarpophalangeal) arthroplasty, have such a procedure scheduled, or anticipate the need for such a procedure during the study.

3. Major surgery (including joint surgery) within 8 weeks prior to screening

4. Subjects with active vasculitis of a major organ system, with the exception of rheumatoid nodules or minor rheumatoid vasculitis lesions of the skin

5. Subjects with current uncontrolled symptoms of severe, progressive, or uncontrolled renal, hepatic hematologic, gastrointestinal, pulmonary, cardiac, neurologic, or cerebral disease, including Cirrhosis with Child-Pugh Class >=2 or COPD (chronic obstructive pulmonary disease) with FEV1 (forced expiratory volume in 1 second) /FVC (forced vital capacity) < 0.6

6. Female subjects who have had a recent breast cancer screening that is suspicious for malignancy and where the diagnosis is not excluded.

h) Subjects who currently abuse drugs or alcohol. i) Subjects with evidence of active or latent bacterial or viral infections at the time of potential enrollment, including HIV.

j) Subjects with herpes zoster or cytomegalovirus (CMV) that resolved less than 2 months before the informed consent document was signed.

k) Subjects who have received any live vaccines within 3 months of the anticipated first dose of study medication.

l) Subjects with any serious bacterial infection within the last 3 months, unless treated and resolved with antibiotics, or any chronic bacterial infection.

m) Subjects at risk for tuberculosis (TB) or not treated for latent TB is tested positive.

n) Subjects who are positive for hepatitis C antibody if the presence of hepatitis C virus was also shown with polymerase chain reaction or recombinant immunoblot assay.

o) Subjects who have abnormal laboratory values

4. Prohibited Treatments and/or Therapies

1. Subjects who have at any time received treatment with any investigational drug within 28 days (or less than 5 terminal half-lives of elimination) of the Day 1 dose.

2. Any concomitant biologic DMARD, such as anakinra.

3. Previous treatment with cell-depleting therapies, including investigational agents, including but not limited to CAMPATH, anti-CD4 (cluster of differentiation 4), anti-CD5, anti-CD3, and anti-CD19.

4. Anti-CD20 treatment within the last 6 months (OK to include if they were dosed > 6 months ago).

5. Treatment with methotrexate, hydroxychloroquine, cyclosporine A, azathioprine, mycophenolate mofetil, within <= 4 weeks prior to baseline.

6. Treatment with etanercept within 2 weeks, infliximab/certolizumab/golimumab/adalimumab with <=8 weeks, anakinra within <=1 week prior to baseline.

7. Previous abatacept use.

8. Treatment with sulfasalazine within < 4 weeks prior to baseline