Safety and Efficacy of Intravenous ACZ885 and Oral Methotrexate Therapy in Patients With Early Rheumatoid Arthritis

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.