A Phase III Multi–center, Double–blind, Placebo–controlled, Parallel Group 24–Week Study to Assess the Efficacy and Safety of Two Dose Regimens of Liquid Certolizumab Pegol as Additional Medication to Methotrexate in the Treatment of Signs and Symptoms of Rheumatoid Arthritis and in Prevention of Joint Damage in Patients with Active Rheumatoid Arthritis who have an Incomplete Response to Methotrexate

INTERVENTION:

Product Name: Certolizumab pegol Product Code: CDP870 Pharmaceutical Form: Solution for injection INN or Proposed

INN:

Certolizumab pegol Current Sponsor code: CDP870 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: range Concentration number: 200 + or ‐‐15 Pharmaceutical form of the placebo: Solution for injection Route of administration of the placebo: Subcutaneous use

CONDITION:

Rheumatoid Arthritis ; Classification code 10039073

PRIMARY OUTCOME:

Main Objective: To compare the efficacy of two dose regimens of liquid formulation certolizumab pegol in combination with MTX to MTX alone in treating the signs and symptoms of patients with active rheumatoid arthritis. Primary end point(s): Primary endpoint and analysis: ; ; The primary efficacy variable is the ACR20 responder rate at Week 24 (Visit 17). The study will be declared successful for the treatment of signs and symptoms objective if at least one of the two dose comparisons to placebo is statistically significant for the ACR20 endpoint. ; ; Treatment comparisons versus placebo for the two certolizumab pegol dose groups will be performed using logistic regression with factors for treatment and country. Statistical tests will be performed two–tailed at the 2.5% level of significance. Secondary Objective: To assess two dose regimens of certolizumab pegol in combination with MTX and MTX alone in: ; ; The safety and tolerability of certolizumab pegol in patients with active RA. ; ; The prevention of joint damage in patients with active RA. ; ; Health Outcomes Measures in patients with active RA. ; ; Improving physical function in patients with active RA. ; ; To characterize the pharmacokinetic profile and immunogenicity of two dose regimens of liquid formulation certolizumab pegol in combination with methotrexate.

INCLUSION CRITERIA:

1. Patients must be at least 18 years old at the screening visit. 2. Patients must have a clear chest X–ray within three months prior to the Baseline visit (negative for TB). 3. Female patients of childbearing potential must have a negative serum pregnancy test at the screening visit and negative urine testing immediately before every certolizumab pegol administration. Females must be surgically sterile, postmenopausal for at least 2 years prior to screening visit, must have undergone tubal ligation or be using an acceptable method of birth control for the duration of the study and for 12 weeks after the last dose of certolizumab pegol. Oral contraceptives must be stable for at least 28 days prior to screening visit. Abstinence is not an acceptable method of contraception for the study. 4. Patients must have a diagnosis of adult–onset RA of at least six months duration but not longer than fifteen years as defined by the 1987 American Coll