A Proof of Concept and Dose Ranging Study in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study is being carried out to investigate if AZD5672 is effective in treating Rheumatoid Arthritis (RA) and if so how it compares to placebo (a substance which does not have any action) and etanercept (a medicine already available to treat Rheumatoid Arthritis) when added to treatment with methotrexate. The purpose of this study is also to find out which dose of AZD5672 is the most effective at treating RA and to find out how well the body tolerates AZD5672 when taken for up to 12 weeks.

Official Title
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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.

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: AZD5672
* Drug: Etanercept
* Drug: Placebo
* Drug: AZD5672
* Drug: AZD5672
* Drug: AZD5672


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of RA with active disease defined as: ≥4 swollen joints and ≥6 tender/painful joints, and either have (blood tests) elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP). At least one of the following: documented history of positive rheumatoid factor (blood test), current presence of positive rheumatoid factor (blood test), baseline radiographic erosion, presence of serum anti-cyclic citrullinated peptide antibodies (bloo Be receiving either: Oral (tablets) or subcutaneous (injection) methotrexate for at least 6 months prior to randomisation. Exclusion Criteria: Any other inflammatory disease in addition to RA that may interfere with the study (e.g. polymyalgia rheumatica, giant cell arteritis, reactive arthritis, etc). Current chronic pain disorders including fibromyalgia and chronic fatigue syndromes.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Drug: Etanercept<br>* 50 mg, subcutaneous injection, weekly<br>* Other names: Enbrel;|
| Experimental: 2<br>20mg | Drug: AZD5672<br>* 20 mg oral, once daily<br>|
| Experimental: 3<br>50mg | Drug: AZD5672<br>* 50 mg oral, once daily<br>|
| Experimental: 4<br>100mg | Drug: AZD5672<br>* 100 mg oral, once daily<br>|
| Experimental: 5<br>150mg | Drug: AZD5672<br>* 150 mg oral, once daily<br>|
| Placebo Comparator: 6<br> | Drug: Placebo<br>* placebo, oral, once daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology 20 Response (ACR20) | The number of participants with greater to or equal to 20% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 12 Weeks' treatment. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| American College of Rheumatology 50 Response (ACR50) | The number of participants with greater to or equal to 50% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 12 Weeks' treatment. | 12 weeks | 
| American College of Rheumatology 70 Response (ACR70) | The number of participants with greater to or equal to 70% improvement in the ACR composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of pain, disease activity and physical function; physician's assessment of disease activity; and CRP) after 12 Weeks' treatment. | 12 weeks | 
| Disease Activity Score (Based on 28 Joint Count) (DAS28) | Change from baseline in the DAS28 composite score (a measure of RA symptoms including: joint swelling and tenderness; patient's assessment of disease activity; and ESR) after 12 Weeks' treatment. A change of zero indicates no effect of treatment and a negative change of 1.2 indicates a clinically important improvement in symptoms. The DAS scale runs from 0 to 10, with the higher scores indicating worse RA symptoms. | Baseline to 12 Weeks | 
| Health Assessment Questionnaire - Disability Index (HAQ-DI) | Change from baseline in HAQ-DI (a measure of patients assessment of physical function scored between zero and 3) after 6 months' treatment, calculated as score at 12 Weeks minus score at baseline. A change of zero indicates no effect of treatment and a negative change of 0.22 or greater indicates an improvement in symptoms. The HAQ-DI scale runs from 0 to 3, with higher scores indicating greater disability. | Baseline to 12 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, RA, AZD5672