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

A 26-week, Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Assess the Response to Treatment (ACR50) and to Determine a Biomarker Profile in Responders to ACZ885 (Anti-interleukin-1beta Monoclonal Antibody) Plus MTX as Compared to MTX Alone in Early Rheumatoid Arthritis Patients

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)

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.