Natalizumab in the Treatment of Rheumatoid Arthritis in Subjects Receiving Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: natalizumab; placebo
Intervention MeSH terms: Natalizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Enrollment: 299.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to determine the safety, tolerability and efficacy of
      natalizumab in subjects diagnosed with moderate to severe rheumatoid arthritis (RA) receiving
      concomitant treatment with methotrexate (MTX). It is thought that natalizumab may stop the
      movement of certain white blood cells, known as lymphocytes, into joint tissue. These cells
      are thought to cause damage in the joints leading to the symptoms of RA.
    

Eligibility criteria:

        Inclusion Criteria:

        Subjects will be eligible to begin study participation if they meet all of the following
        inclusion criteria:

          -  Subject is able to read, understand, and voluntarily sign the approved Informed
             Consent form prior to the performance of any study-specific procedures;

          -  Male or female subjects, ≥18 to ≤75 years of age, who has a diagnosis of rheumatoid
             arthritis Functional Class 1 to 3 by the 1987 Revised American Rheumatism Association
             Criteria for the Classification of Rheumatoid Arthritis for at least 6 months prior to
             screening;

          -  Subject is on a stable dose of MTX of at least 10 mg/week for ≥3 months prior to
             randomization (Month 0) without an adequate response;

          -  Female subjects of childbearing potential agree to use adequate, contraceptive methods
             (either intrauterine device [IUD], oral or depot contraceptive, or barrier plus
             spermicide). Female subjects of childbearing potential use adequate contraception for
             at least 2 months prior to study entry and continue contraception for at least 3
             months after their last infusion of study drug;

          -  Subject is willing and able to complete all planned study procedures;

          -  Subject has at least 10 painful/tender and 6 swollen joints at the Month 0 (Baseline)
             visit;

          -  Subject has an elevated CRP level (defined as >2.87 mg/L) at Screening.

        Exclusion Criteria:

        Subjects will be excluded from the study if they meet any of the following exclusion
        criteria:

          -  Subject is pregnant or lactating;

          -  Subject who has experienced an inadequate therapeutic response after at least 3 months
             of treatment with at least one TNF-alpha inhibitor;

          -  Subject who has received treatment with anakinra;

          -  Subject who has received prior treatment with natalizumab;

          -  Subject does not meet the following criteria regarding concomitant medications for RA:

          -  Use of any oral steroid exceeding 10 mg/day of prednisone (or equivalent dose) and not
             administered at a stable dose for at least 1 month prior to randomization (Month 0);

          -  Use of any NSAIDs unless stable for at least 1 month prior to randomization (Month 0);

          -  Use of other anti-arthritic treatments, including approved or experimental oral,
             topical, or injectable biologics or drugs, or devices within 1 month prior to
             randomization (Month 0);

          -  Intra-articular corticosteroid injections within 1 month prior to randomization (Month
             0);

          -  Treatment with any TNF-alpha inhibitor within 2 months prior to randomization (Month
             0);

          -  Subject who is expected to be unavailable for the duration of the trial, likely to be
             noncompliant with the Protocol, or felt to be unsuitable by the Investigator for any
             other reason;

          -  Subject who has a history of a malignancy (other than basal cell carcinoma of the
             skin);

          -  Subject who has a history of clinically significant and/or persistent
             gastrointestinal, pulmonary, chronic infection, cardiovascular, renal, hepatic,
             neurological, dermatological, immunological, major psychiatric (including drug or
             alcohol abusers) or hematological illness, which, in the opinion of the Investigator
             placed the subject at unacceptable risk for participation in the study;

          -  Subject who has any laboratory test at Screening considered significantly abnormal. An
             alanine transaminase (ALT) or aspartate transaminase (AST) ≥1.5 x upper limits of
             normal (ULN) and cytopenia (included any of the following: WBC <3.5 x 1000/uL;
             hemoglobin [Hb] <8 g/dL; platelets <100 x 1000/uL; and/or neutrophils absolute <1.0 x
             1000/uL) were considered significantly abnormal;

          -  Subject who intends to donate blood or blood products during the period of the study
             or within 1 month following completion of the study;

          -  Subject who has a positive tuberculosis (TB) skin test at Screening or within the 30
             days prior to Screening (defined as ≥10 mm induration);

          -  Subject who plans or requires any surgical procedure during the study treatment
             period.