Namilumab vs Adalimumab in Participants With Moderate to Severe Early Rheumatoid Arthritis Inadequately Responding to Methotrexate
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Namilumab; Adalimumab; Methotrexate; Folic Acid
Intervention description: Namilumab injection; Adalimumab SC injection; Methotrexate tablet; Folic Acid Tablet
Intervention MeSH terms: Folic Acid; Adalimumab; Methotrexate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Drug Therapy

Summary:

      The purpose of this study is to evaluate the efficacy and safety of namilumab in combination
      with existing methotrexate (MTX) therapy over 24 weeks in participants with moderate to
      severe early rheumatoid arthritis (RA), diagnosed within 6 months and inadequately controlled
      by MTX alone.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Is diagnosed with adult onset rheumatoid arthritis (RA) as defined by the 2010 The
             American College of Rheumatology (ACR)/The European League Against Rheumatism criteria
             for the classification of RA within 6 months prior to Screening Visit.

          -  Has active disease defined as:

               1. swollen joint count ≥4 and tender joint count ≥4 (referred to the 28 joint-count
                  system) at Screening and Baseline Visits, and

               2. C-reactive protein ≥4.3 mg/L and erythrocyte sedimentation rate ≥28 mm/hr at
                  Baseline Visits, and

               3. imaging (ultrasound power doppler) evidence of moderate to severe inflammation of
                  at least 1 joint of the dominant hand metacarpophalangeal (MCP) and/or wrist) at
                  Screening and Baseline Visits.

          -  Is receiving current treatment with Methotrexate (MTX) for RA.

          -  Received MTX for at least 3 months prior to the Screening Visit.

          -  Received treatment with MTX ≥15 to 25 mg/week at a stable dose via the same route of
             administration and formulation for at least 8 weeks prior to the Baseline Visit, OR

          -  Participants on a stable dose for at least 8 weeks of MTX of ≥7.5 mg/week, if the MTX
             dose has been reduced for reasons of documented intolerance to MTX.

          -  Is willing to continue or initiate treatment with oral folic acid (at least 5 mg/week)
             or equivalent and be treated during the entire trial (mandatory co-medication for MTX
             treatment).

          -  Has a posterior, anterior, and lateral chest x-ray obtained within the last 3 months
             before Screening or at the Screening visit without any signs of clinically significant
             pulmonary disease.

        Exclusion Criteria:

          -  Has received biologic disease-modifying antirheumatic drugs for the treatment of RA.

          -  Have a history of or currently inflammatory joint disease other than RA (e.g., gout,
             reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, or Lyme
             disease) or other systemic autoimmune disorder (eg, systemic lupus erythematosus,
             inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective
             tissue disease, or other overlap syndrome).

          -  Has any major systemic features of RA, for example, Felty's syndrome, vasculitis, or
             interstitial fibrosis of the lungs.

          -  Diagnosed with primary fibromyalgia that would make it difficult to appropriately
             assess RA activity for the purposes of this study or a diagnosis of any systemic
             inflammatory condition other than RA.

          -  Has a history of juvenile idiopathic arthritis or RA onset prior to age 16 years.

          -  Required to take excluded medications

          -  Not willing to take folic/folinic acid (as part of MTX regimen, according to
             country-specific practices) in order to minimize toxicity.

          -  Has an underlying condition that predisposes to infections (e.g., immunodeficiency,
             poorly controlled diabetes history, splenectomy).

          -  Has a history of clinically significant interstitial lung disease, for example,
             history of chronic or recurrent pulmonary infection where macrophages are important
             for the clearance of the infection, for example, pneumocystis carinii pneumonia,
             allergic bronchopulmonary aspergillosis, nocardia infections, Actinomyces infection.

          -  Presence or history of active tuberculosis (TB) or latent TB infection, where no
             anti-TB treatment has been given or where successful completion of an appropriate
             course of anti-TB therapy cannot be documented.

          -  A positive QuantiFERON-TB Gold test and/or evidence of active or latent TB by chest
             x-ray at Screening Visit, not accompanied by initiation of an approved regimen of
             anti-TB therapy at least 12 months prior to the Baseline Visit.

          -  Has a known history of infection with hepatitis B virus, hepatitis C virus, or human
             immunodeficiency virus (HIV), or has serological findings at the Screening Visit which
             indicate active or latent hepatitis B, hepatitis C or HIV infection.

          -  Has a clinically relevant decrease in lung function at Screening, as defined by an
             oxygen saturation as measured by pulse oximetry (SpO2) <94% at rest.

          -  Has evidence of clinically significant respiratory disease on the basis of review the
             data from participants' respiratory assessments including chest x-ray, pulmonary
             function test (forced expiratory volume in 1 second [FEV1] and forced vital capacity
             [FVC]) by spirometry performed at Screening). The participants must have SpO2 ≥94%,
             FEV1 and/or FVC ≥60% of predicted values at Screening or at Baseline and no
             uncontrolled lung disease. Participant's treatment that has been modified to control
             lung disease within 24 weeks prior to Screening is exclusionary.

          -  Has a history of severe chronic obstructive pulmonary disease (COPD) and/or history of
             severe COPD exacerbation(s), or a history of asthma with exacerbations requiring
             hospitalization, within the last 12 months prior to the Screening Visit.

          -  Has an estimated glomerular filtration rate (eGFR) of less than 60
             mL/min/1.73m2.History of MTX-associated lung toxicity.

          -  Has a history or evidence of a clinically significant disorder (including but not
             limited to cardiopulmonary, oncologic, renal, metabolic, hematologic or psychiatric),
             condition or disease that, in the opinion of the investigator and Takeda physician,
             would pose a risk to participant safety or interfere with the study evaluation,
             procedures or completion.

          -  Has any significant cardiac disease (eg, coronary artery disease with unstable angina,
             coronary heart failure New York Heart Association Class III and IV, familial long QT
             syndrome).

          -  Has a history of cancer within the last 10 years except for basal cell or squamous
             cell carcinomas of the skin or in situ carcinoma of the cervix treated and considered
             cured.

          -  Has a severe psychiatric or neurological disorder.