A Randomised, Double-Blind, Placebo-Controlled, Phase IIb Dose-Ranging Study (with Open-label Etanercept Treatment Group) to Investigate Efficacy, Safety and Pharmacokinetics of AZD5672 Administered for 12 Weeks to Rheumatoid Arthritis Patients Receiving Methotrexate - Escape

Conditions: Male and female patients over 18 years of age, with active RA despite current treatment with methotrexate. All patients will continue with background methotrexate therapy.
MedDRA version: 9.1Level: LLTClassification code 10039073Term: Rheumatoid arthritis

Registration Number: EUCTR2007-007539-14-IT

Lead Sponsor: ASTRAZENECA

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 360

Inclusion Criteria

Provision of informed consent (including PK subset consent, as applicable). 2. Male or female aged 18 or over. Note: Women of child-bearing potential may be included only if highly effective contraception is in place (see Section 3.3.4 and Appendix K) and patients are fully aware of the information relating to the potential for reprotoxicity as detailed in the informed consent form. Males who are involved in the study must agree to abstain from procreative sex during the study and for 12 weeks after the last dose of study medication. 3. Diagnosis of RA after the age of 16 according to the revised (1987) criteria of the American College of Rheumatology (see Appendix E).4. Have active RA defined as: − ≥4 swollen joints and ≥6 tender/painful joints (from 28 joint count, see Section 4.6.1.1) and either: ESR ≥28 mm/h or, CRP ≥10 mg/L. 5. At least one of the following: − Documented history of positive rheumatoid factor − Current presence of rheumatoid factor − Baseline radiographic erosion − Presence of serum anti-cyclic citrullinated peptide antibodies (anti-CCP). 6. Oral or subcutaneous or intramuscular methotrexate for at least 6 months prior to randomisation. The dose and means of administering methotrexate must have been stable between 5 mg and 25 mg per week for at least 6 weeks prior to randomisation. For inclusion in the genetic research, patients must fulfil the following criterion: 1. Provision of informed consent for genetic research If a patient declines to participate in the genetic research, there will be no penalty or loss of benefit to the patient. The patient will not be excluded from other aspects of the study described in this clinical study protocol, so long as they consent.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Pregnant or lactating females (restrictions and procedures concerned with managing the risk of pregnancy/conception for males and females are provided in Section 3.3.4 and 9.4). 2. Any systemic inflammatory condition in addition to RA that may interfere with the interpretation of the outcome data (examples include but are not limited to polymyalgia rheumatica, giant cell [including temporal] arteritis, reactive arthritis). 3. Current chronic pain disorders, including fibromyalgia and chronic fatigue syndromes. 4. American College of Rheumatology functional class IV (see Appendix F) or wheelchair/bed-bound. 5. Patient unable to comply with the local approved product information for etanercept. Note: any patients randomised to receive etanercept will be confirmed as negative for LTBI prior to initiation of treatment. If the patient has had a negative TB test in the month prior to Visit 1, the result of that test will stand and the test does not need to be repeated. Patients who have a positive test result should be discontinued, see Section 3.3.5.1). Note: Where a local label is not available, then the label applicable to the supplied drug will apply. 6. Patients who have previously failed to respond to treatment with more than 1 biological agent. 7. Patients who in the opinion of the investigator have active TB as defined by clinical history and/or chest X-ray. 8. Patients who fail to comply with or are unlikely to stay compliant with the restrictions on prior and concomitant medication usage as provided in Section 3.7. 9. Clinical or biochemical evidence of active infection with hepatitis B or hepatitis C (carriers ie, those with positive serology but no evidence of active disease may be included). 10. Values of aspartate aminotransferase (AST), alanine aminotransferase (ALT) or bilirubin >2 x upper limit of normal (ULN) at Visit 1. Note: If a potential patient has liver function only marginally outside these limits (as judged by the investigator), the patient may at the investigator?s discretion be brought back to study centre and retested not less than 2 weeks later and may be enrolled in the trial if the test(s) is then within the prescribed limit. 11. History of excessive alcohol consumption or chronic alcohol induced disease. See the protocol on p. 32-33

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The primary objective of this study is to evaluate the effect of AZD5672 (20, 50, 100 and 150 mg once daily) on the signs and symptoms of rheumatoid arthritis (RA) in patients on background methotrexate therapy,;Primary end point(s): The primary effucacy variable of this trial is the proportion of patients who achieve ab ACR20 response at week 12.;Secondary Objective: The secondary objectives of the study are: To further evaluate the effect of AZD5672 on the signs and symptoms of rheumatoid arthritis in patients on background methotrexate therapy as measured by: − ACR20 response at 4 and 8 weeks − ACR50, ACR70 and Hybrid ACR response (4, 8, and 12 weeks) − Individual components of the ACR response criteria (4, 8, and 12 weeks) − Erythrocyte Sedimentation Rate (4, 8, and 12 weeks) − DAS28 scores and response rates (4, 8, and 12 weeks). To evaluate the safety and tolerability of AZD5672 in patients on background methotrexate therapy

Secondary Outcome Measures

Name	Time	Method

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