Study of CE-224,535 A Twice Daily Pill To Control Rheumatoid Arthritis In Patients Who Have Not Totally Improved With Methotrexate

Study Overview
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Brief Summary
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CE-224,535 is known to block a chemical that acts as a gateway to some of your immune cells. Blocking this gateway prevents the cells from pushing out 2 chemicals called IL-1 and IL-18 that are known to cause some of the inflammation seen in rheumatoid arthritis. It is hoped that taking this drug will reduce the symptoms of rheumatoid arthritis

Official Title
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A PHASE 2A, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY OF CE-224,535, AN ANTAGONIST OF THE P2X7 RECEPTOR, IN THE TREATMENT OF THE SIGNS AND SYMPTOMS OF RHEUMATOID ARTHRITIS IN SUBJECTS WHO ARE INADEQUATELY CONTROLLED ON METHOTREXATE

Conditions
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Arthritis, Rheumatoid

Intervention / Treatment
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* Drug: CE-224,535
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Active rheumatoid arthritis Incomplete response to methotrexate Exclusion Criteria: Must not be on biologic therapies No recent infections

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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 |
| --- | --- |
| Experimental: Active<br> | Drug: CE-224,535<br>* 500 mg po BID<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* no active ingredient<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Week 12 | ACR20 response: compared to baseline, greater than or equal to (>=) 20 percent (%) improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Week 2, 4 and 8 | ACR20 response: compared to baseline, >=20% improvement in tender joint count; >= 20% improvement in swollen joint count; and >= 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). | Week 2, 4, 8 | 
| Percentage of Participants With American College of Rheumatology 50% (ACR50) Response | ACR50 response: compared to baseline, >=50% improvement in tender joint count; >= 50% improvement in swollen joint count; and >= 50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). | Week 2, 4, 8, 12 | 
| Percentage of Participants With American College of Rheumatology 70% (ACR70) Response | ACR70 response: compared to baseline, >=70% improvement in tender joint count; >= 70% improvement in swollen joint count; and >= 70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of pain; participant global assessment of disease activity; physician global assessment of disease activity; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and C-Reactive Protein (CRP). | Week 2, 4, 8, 12 | 
| Number of Tender/Painful and Swollen Joints | Number of tender/painful joints was determined by examining 28 joints and identified the joints that were painful under pressure or to passive motion. The number of tender joints was recorded on the joint assessment form at each visit, no tenderness = 0, tenderness = 1. Number of swollen joints was determined by examination of 28 joints and identifying when swelling was present. The number of swollen joints was recorded on the joint assessment form at each visit, no swelling = 0, swelling =1. | Baseline, Week 2, 4, 8, 12 | 
| Physician Global Assessment (PGA) of Arthritis | Physician global assessment of arthritis was measured on a 0 to 100 millimeter (mm) Visual Analog Scale (VAS), with 0 mm= very good and 100 mm= very poor. This was an evaluation based on the participant's disease signs, functional capacity and physical examination. | Baseline, Week 2, 4, 8, 12 | 
| Patient's Global Assessment of Arthritis | Participants answered: Considering all the ways your arthritis affects you, how are you feeling today? Participants responded by using a 0 to 100 mm VAS, with 0 mm= very well and 100 mm= very poorly. | Baseline, Week 2, 4, 8, 12 | 
| Patient's Global Assessment of Arthritic Pain | Participants measured their pain at the time of assessment on a 0 to 100 mm VAS, with 0 mm= no pain and 100 mm= most severe pain. | Baseline, Week 2, 4, 8, 12 | 
| Health Assessment Questionnaire-Disability Index (HAQ-DI) Score | Health Assessment Questionnaire-Disability Index (HAQ-DI): participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item scored on 4-point scale from 0 to 3: 0= no difficulty; 1= some difficulty; 2= much difficulty; 3= unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0= least difficulty and 3= extreme difficulty. | Baseline, Week 2, 4, 8, 12 | 
| Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP]) | DAS28-3 (CRP) was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (milligram per liter [mg/L]). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-3 (CRP) less than or equal to (<=) 3.2 implied low disease activity and >3.2 to 5.1 implied moderate to high disease activity, and DAS28-3 (CRP) <2.6 = remission. | Baseline, Week 2, 4, 8, 12 | 
| C-Reactive Protein (CRP) | The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. | Baseline, Week 2, 4, 8, 12 | 
| Incidence of Withdrawal Due to Lack of Efficacy | Number of participants who withrew due to lack of efficacy were reported. | Week 2, 4, 8, 12, 14 | 
| Time to Withdrawal Due to Lack of Efficacy |  | Baseline up to Week 14 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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rheumatoid arthritis DMARD methotrexate