Safety and Efficacy of Intravenous ACZ885 and Oral Methotrexate Therapy in Patients With Early Rheumatoid Arthritis
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Canakinumab (investigational); Placebo; Methotrexate (MTX)
Intervention description: Canakinumab was supplied in 6 mL colorless glass vials each containing nominally 150 mg canakinumab (with 20% overfill). The vials were kept at 2-8°C. At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.; Matching placebo was supplied in form of a lyophilized cake (Powder for Solution for Infusion). At the investigator's site, solutions for infusion were prepared depending on the volume and dose administered.; Methotrexate (MTX) was supplied in tablet form, each of 2.5 mg strength.
Intervention MeSH terms: Methotrexate
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 78.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: ACR20, ACR50, ACZ885 (anti-interleukin-1beta monoclonal antibody), rheumatoid arthritis, methotrexate

Summary:

      This study was intended to evaluate the safety and efficacy of intravenous (IV) ACZ885 and
      oral methotrexate (MTX) therapy in patients with early rheumatoid arthritis (RA)
    

Eligibility criteria:

        Inclusion Criteria:

          -  Male and female patients of 18 to 75 years of age (inclusive)

          -  Recent definite diagnosis of rheumatoid arthritis (RA) (<3 years since diagnosis),
             classified by American Rheumatism Association 1987 revised criteria.

          -  Candidate for methotrexate (MTX) or biologic due to erosive arthritis, with no
             contraindications to such therapy, including:

          -  Negative tuberculin skin test reaction

          -  Normal chest X-ray (within the last year) prior to possibility of receiving MTX (r/o
             lung fibrosis).

          -  Active disease: at least 6 swollen and 6 painful tender joints of 28 joint count,

          -  Vital signs should be within the following ranges:

          -  18-59 years of age: oral temperature between 35.0-37.5 °C systolic blood pressure,
             90-140 mm Hg diastolic blood pressure, 50-90 mm Hg pulse rate, 40 - 90 beats per
             minute

          -  60-75 years of age: oral temperature between 35.0-37.5 °C systolic blood pressure,
             100-160 mm Hg diastolic blood pressure, 50-100 mm Hg pulse rate, 50 - 100 beats per
             minute

          -  Women of child-bearing potential willing to practice double-barrier contraception
             during the study for at least 3 months following last study drug administration.
             Postmenopausal women must have no regular menstrual bleeding for at least 1 year prior
             to inclusion. Surgically sterilized women at least 6 months prior to screening.

        Male patients must be using a double-barrier local contraception and refrain from fathering
        a child in the 3 months following last study drug administration.

          -  Weight: at least 45 kg; body mass index (BMI) within the range of 18 to 34.

          -  Oral corticosteroids are permitted as long as patients are on a stable dose (up to 10
             mg) for at least 4 weeks before study start.

        Exclusion Criteria:

          -  Unable to have Magnetic Resonance Imaging (MRI) of wrist.

          -  Patients with magnetizable metal parts/devices on and in the body that could interfere
             with the MRI

          -  Patients with an unstable active medical condition that could impair evaluation of
             study results.

          -  Previous treatment with biological therapy or MTX.

          -  Limited kidney function (creatinine clearance under 60 ml/min)

          -  Previous treatment with other disease-modifying anti-rheumatic drugs such as
             sulfasalazine, hydroxychloroquine within 4 weeks of screening.

          -  Corticosteroids injections into joints within 4 weeks prior to screening.

          -  Participation in any clinical investigation within 4 weeks prior to study start or
             longer if required by local regulations, and for any other limitation of participation
             based on local regulations.

          -  Blood donation or loss of > 400 mL within 8 weeks before study start, or longer if
             required by local regulation.

          -  Significant illness within 2 weeks of study start.

          -  Past personal or family medical history of clinically significant ECG abnormalities or
             cardiac issues.

          -  History of:

               -  fainting, orthostatic hypotension, sinus arrhythmia asthma and chronic
                  obstructive pulmonary disease, clinically significant drug allergy or urticaria,
                  eczematous dermatitis, and/or known hypersensitivity to the study drug or drugs
                  similar to the study drug.

               -  disease of the blood building system, serious or active infections, gastric
                  ulcers.

               -  surgical or medical condition which might significantly alter the absorption,
                  distribution, metabolism or excretion of drugs or which may jeopardize the
                  patient in case of participation in the study.

               -  immunodeficiency diseases, including a positive Human Immunodeficiency Virus
                  (HIV) (ELISA and Western blot) test result.

               -  positive Hepatitis B surface antigen (HBsAg) or Hepatitis C test result.

               -  drug or alcohol abuse within the 12 months prior to dosing or evidence of such
                  abuse.