Study to Investigate the Safety and Efficacy of Tregalizumab in Subjects (MTX-IR) With Active Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Tregalizumab; Placebo
Intervention description: humanized anti-CD4 mAb; identical end formulation buffer
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 321.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: inadequate response to MTX; Methotrexate; rheumatoid Arthritis; Phase 2b

Summary:

      The purpose of this study is to determine the efficacy and safety of three different
      Tregalizumab doses in combination with Methotrexate (MTX) in subjects who have active
      rheumatoid arthritis and an inadequate response to MTX alone.

      The overall study duration is 24 weeks followed by a 24 week extension phase.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Subject demonstrates active RA according to the 1987 American College of Rheumatology
             (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) classification criteria
             for RA with functional class I-III for ≥6 months.

          2. Subject receives oral or parenteral MTX treatment for ≥12 weeks (overall), with an
             unchanged mode of application and stable MTX dose of ≥15 mg per week (or ≥12.5 mg per
             week in case of MTX intolerance), but no more than the highest locally approved dose
             for RA, for ≥8 weeks prior to baseline. The dose of MTX is expected to remain stable
             throughout the study and may be adjusted only for safety reasons. If applicable, the
             dose of folic acid must be unchanged for ≥8 weeks prior to baseline.

          3. Subject meets the following two criteria at both screening and baseline: - At least 6
             swollen joints at 28-joint assessment. - At least 6 tender joints at 28-joint
             assessment.

          4. Subject has an erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) above
             the upper limit of normal (ULN) at screening. These tests may be repeated once during
             the screening period at the discretion of the investigator.

          5. Subject is ≥18 and ≤75 years of age.

          6. Subject has a body mass index ≥18 and ≤35 kg/m².

          7. Subject receives treatment with corticosteroids ≤10 mg prednisone equivalent, stable
             for at least 4 weeks prior to baseline and during the study, if applicable.

          8. Subject receives treatment with non-steroidal anti-inflammatory drugs (NSAIDs), stable
             for at least 2 weeks prior to baseline and during the study, if applicable.

          9. Female subjects of childbearing potential: has both a negative serum pregnancy test at
             screening and a negative urine pregnancy test at baseline.

         10. Subject is judged to be in good general health as determined by the investigator based
             upon the results of medical history, laboratory profile, physical examination, chest
             X-ray (within 3 months before screening date is acceptable), and 12-lead
             electrocardiogram (ECG).

         11. Subject has a cluster of differentiation 4 (CD4) cell count of > 400/µl at screening.

        Exclusion Criteria:

          1. Subject has previous exposure to any systemic biologic therapy (e.g., etanercept,
             adalimumab, rituximab, abatacept, tocilizumab), to Janus kinase (JAK) or spleen
             tyrosine kinase (SYK) inhibitors, or to Tregalizumab. Previous treatment with an
             anti-TNF agent is allowed only, if all of the following criteria apply: - treatment
             was stopped for reasons other than lack of efficacy or adverse events (AEs) -
             treatment was stopped at least 12 weeks or five half-lives of the compound prior to
             baseline (whichever is longer), and - the treatment period did not exceed 6 weeks.

          2. Subject received treatment with conventional disease-modifying anti-rheumatic drugs
             (DMARDs) apart from MTX in the 12 weeks prior to baseline, and for DMARD leflunomide
             in the 24 weeks prior to baseline (except where specific leflunomide wash-out
             procedures were completed, following applicable guidelines).

          3. Subject has been treated with intra-articular or parenteral administration of
             corticosteroids in the 4 weeks prior to baseline. Inhaled corticosteroids for stable
             medical conditions are allowed.

          4. Subject has undergone joint surgery in the 12 weeks prior to baseline (at joints to be
             assessed within the study) or has undergone major surgery (e.g., abdominal surgery) in
             the 8 weeks prior to baseline.

          5. Subject has a history of acute inflammatory joint disease of an origin other than RA
             or subject has any other rheumatic disease other than RA (e.g., mixed connective
             tissue disease, seronegative spondylarthropathy, psoriatic arthritis, Reiter's
             syndrome, fibromyalgia, systemic lupus erythematosus or any arthritis with onset prior
             to age 17 years). However, subjects may have secondary Sjögren's syndrome.