Study of MDX-1100 (Anti-CXCL10 Human Monoclonal Antibody) in Combination With Methotrexate in Subjects With Active Rheumatoid Arthritis (RA)

• Status: Completed
• Trial end date: 2009-05-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to:

1. determine the American College of Rheumatology (ACR) 20 response rate at Day 85 in subjects with active rheumatoid arthritis(RA) administered MDX 1100 with methotrexate (MTX); and

2. determine the tolerability and safety of multiple doses of MDX-1100 in combination with MTX in subjects with active RA.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Bristol-Myers Squibb
• Treatments: Antibodies; Antibodies, Monoclonal; Methotrexate

Criteria

Inclusion Criteria:

• Must meet the ACR criteria for RA

• Must have active RA, characterized by at least 6 out of 66 swollen joints and 6 out of 68 tender joints, and at least 2 of the following: a serum C-reactive protein level greater than the upper limit of normal, an erythrocyte sedimentation rate >= 28 mm per hour, or morning stiffness > 45 minutes

• Seropositive for rheumatoid factor, as defined by a plasma rheumatoid factor level of at least 20 IU per milliliter and/or be seropositive for anti-cyclic citrullinated peptide antibody

• Must be on MTX (10 to 25 mg weekly) for at least 6 months receiving a stable dose for 42 days before randomization and no anticipated change in MTX dose while on study

• Low-dose corticosteroids and NSAIDs are permitted at study entry and must have been stable for at least 28 days before randomization

• All other disease modifying non-biologic anti-rheumatic drugs (DMARDs) must have been discontinued at least 28 days prior to randomization except for leflunomide (discontinued at least 60 days before randomization). Etanercept (discontinued at least 28 days prior to randomization) and infliximab, adalimumab, and abatacept (discontinued at least 56 days prior to randomization)

• Screening laboratory values

• Hemoglobin ≥ 8.5 g/dL

• White blood cell (WBC) ≥ 3000/mm³

• Neutrophils ≥ 1.5x10(9)/L

• Platelets ≥ 125x10(9)/L

• Serum creatinine < 2 mg/dL

• Aspartate aminotransferase (AST) ≤ 2xULN

• Alanine aminotransferase (ALT) ≤ 2xULN

• Women must be postmenopausal (> 12 months without menses) or surgically sterile or using effective contraception for at least 4 weeks prior to the anticipated Visit 2 date and agree to continue contraception for the duration of their participation in the study

• Sexually active male subjects must use a barrier method of contraception during the course of the study.

Exclusion Criteria:

• Prior treatment with B cell depleting therapy

• Any other monoclonal antibody or immunoglobulin-based fusion proteins ≤ 8 weeks prior to randomization

• Any other experimental treatment ≤ 4 weeks prior to randomization

• Primary or secondary immunodeficiency

• Any other autoimmune disease other than RA (except concurrent Sjogren's syndrome or hypothyroidism)

• Complications of RA including:

• Active rheumatoid vasculitis

• Bed bound or wheelchair bound

• Clinically significant pulmonary fibrosis

• Felty's syndrome

• Any history of malignancy, excluding adequately treated and cured basal or squamous cell carcinoma of the skin, or cervical carcinoma in situ

• Active major psychiatric disease

• Evidence of acute or chronic infection

• Clinically significant cardiac disease requiring medication, unstable angina, myocardial infarction within 6 months of randomization, or congestive heart failure

• Arrhythmia requiring active therapy, with the exception of clinically insignificant extrasystoles, or minor conduction abnormalities;

• History of cerebrovascular disease requiring medication/treatment;

• Concomitant anticoagulation therapy or a known bleeding disorder

• Seizure disorder requiring active therapy

• Known drug or alcohol abuse

• Pregnant or nursing