Back to resultsStudy of CE-224,535 A Twice Daily Pill To Control Rheumatoid Arthritis In Patients Who Have Not Totally Improved With Methotrexate
Primary Purpose
Arthritis, Rheumatoid
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
CE-224,535
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Arthritis, Rheumatoid focused on measuring rheumatoid arthritis DMARD methotrexate
Eligibility Criteria
Inclusion Criteria:
- Active rheumatoid arthritis
- Incomplete response to methotrexate
Exclusion Criteria:
- Must not be on biologic therapies
- No recent infections
Sites / Locations
- Arizona Arthritis & Rheumatology Associates, P.C.
- Omega Research Consultants LLC
- Florida Arthritis Center
- Tampa Medical Group, PA
- American Health Network
- Best Clinical Trials, LLC (Administrative Only)
- George Stanley Walker, MD
- Majid Abdul Jawad, MD
- The Arthritis and Osteoporosis Center of Maryland
- University Physicians
- University of Missouri-Columbia
- Arthritis Center of Reno
- New Horizons Clinical Research
- Arthritis Northwest
- Clínica Santa María, Sección Reumatología
- Revmatologicka ambulance
- Revmatologicky ustav
- Revmatologicka ambulance
- Inha University Hospital, Medicine/Rheumatology
- Pusan National University Hospital, Rheumatology, Internal Medicine
- Investigadores Clinicos Asociados
- Krakowskie Centrum Medyczne NZOZ
- Zaklad Reumatologii i Immunologii Klinicznej
- Oddzial Reumatologiczno-Rehabilitacyjny IIR Ortopedyczno-Rehabilitacyjny
- Hospital Nuestra Señora de La Esperanza
- Complexo Hospitalario Universitario A Coruña
- Hospital General Universitario Gregorio Marañon
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Active
Placebo
Arm Description
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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).
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).
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).
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.
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.
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.
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.
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.
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.
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.
Incidence of Withdrawal Due to Lack of Efficacy
Number of participants who withrew due to lack of efficacy were reported.
Time to Withdrawal Due to Lack of Efficacy
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00628095
Brief Title
Study of CE-224,535 A Twice Daily Pill To Control Rheumatoid Arthritis In Patients Who Have Not Totally Improved With Methotrexate
Official Title
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2022
Overall Recruitment Status
Completed
Study Start Date
April 7, 2008 (Actual)
Primary Completion Date
February 4, 2009 (Actual)
Study Completion Date
February 4, 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Arthritis, Rheumatoid
Keywords
rheumatoid arthritis DMARD methotrexate
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Active
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
CE-224,535
Intervention Description
500 mg po BID
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
no active ingredient
Primary Outcome Measure Information:
Title
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Week 12
Description
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).
Time Frame
Week 12
Secondary Outcome Measure Information:
Title
Percentage of Participants With American College of Rheumatology 20% (ACR20) Response at Week 2, 4 and 8
Description
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).
Time Frame
Week 2, 4, 8
Title
Percentage of Participants With American College of Rheumatology 50% (ACR50) Response
Description
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).
Time Frame
Week 2, 4, 8, 12
Title
Percentage of Participants With American College of Rheumatology 70% (ACR70) Response
Description
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).
Time Frame
Week 2, 4, 8, 12
Title
Number of Tender/Painful and Swollen Joints
Description
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.
Time Frame
Baseline, Week 2, 4, 8, 12
Title
Physician Global Assessment (PGA) of Arthritis
Description
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.
Time Frame
Baseline, Week 2, 4, 8, 12
Title
Patient's Global Assessment of Arthritis
Description
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.
Time Frame
Baseline, Week 2, 4, 8, 12
Title
Patient's Global Assessment of Arthritic Pain
Description
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.
Time Frame
Baseline, Week 2, 4, 8, 12
Title
Health Assessment Questionnaire-Disability Index (HAQ-DI) Score
Description
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.
Time Frame
Baseline, Week 2, 4, 8, 12
Title
Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 [CRP])
Description
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.
Time Frame
Baseline, Week 2, 4, 8, 12
Title
C-Reactive Protein (CRP)
Description
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.
Time Frame
Baseline, Week 2, 4, 8, 12
Title
Incidence of Withdrawal Due to Lack of Efficacy
Description
Number of participants who withrew due to lack of efficacy were reported.
Time Frame
Week 2, 4, 8, 12, 14
Title
Time to Withdrawal Due to Lack of Efficacy
Time Frame
Baseline up to Week 14
Other Pre-specified Outcome Measures:
Title
CE-224,535 Plasma Concentrations
Description
Nominal times were used for summarizing the pharmacokinetic results (0 hours at randomization [Day 1] and Week 4 [pre-dose]; 1 hour at Week 2 [post-dose]; 2 hours at randomization [post-dose on Day 1]; and 3 hours at Week 2 [post-dose] and Week 4 [post-dose]).
Time Frame
0 hour (pre-dose), 2 hours post-dose at Day 1; 1, 3 hours post-dose at Week 2; 0 hour (pre-dose), 3 hours post-dose at Week 4
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
99 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Active rheumatoid arthritis
Incomplete response to methotrexate
Exclusion Criteria:
Must not be on biologic therapies
No recent infections
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
Arizona Arthritis & Rheumatology Associates, P.C.
City
Mesa
State/Province
Arizona
ZIP/Postal Code
85202
Country
United States
Facility Name
Omega Research Consultants LLC
City
DeBary
State/Province
Florida
ZIP/Postal Code
32713
Country
United States
Facility Name
Florida Arthritis Center
City
Lake Mary
State/Province
Florida
ZIP/Postal Code
32746
Country
United States
Facility Name
Tampa Medical Group, PA
City
Tampa
State/Province
Florida
ZIP/Postal Code
33614
Country
United States
Facility Name
American Health Network
City
Avon
State/Province
Indiana
ZIP/Postal Code
46123
Country
United States
Facility Name
Best Clinical Trials, LLC (Administrative Only)
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
George Stanley Walker, MD
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
Majid Abdul Jawad, MD
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70115
Country
United States
Facility Name
The Arthritis and Osteoporosis Center of Maryland
City
Frederick
State/Province
Maryland
ZIP/Postal Code
21702
Country
United States
Facility Name
University Physicians
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65203
Country
United States
Facility Name
University of Missouri-Columbia
City
Columbia
State/Province
Missouri
ZIP/Postal Code
65212
Country
United States
Facility Name
Arthritis Center of Reno
City
Reno
State/Province
Nevada
ZIP/Postal Code
89502
Country
United States
Facility Name
New Horizons Clinical Research
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45242
Country
United States
Facility Name
Arthritis Northwest
City
Spokane
State/Province
Washington
ZIP/Postal Code
99204-2336
Country
United States
Facility Name
Clínica Santa María, Sección Reumatología
City
Providencia
State/Province
Santiago, RM
ZIP/Postal Code
7530206
Country
Chile
Facility Name
Revmatologicka ambulance
City
Ceska Lipa
ZIP/Postal Code
470 01
Country
Czechia
Facility Name
Revmatologicky ustav
City
Praha 2
ZIP/Postal Code
128 50
Country
Czechia
Facility Name
Revmatologicka ambulance
City
Praha 4
ZIP/Postal Code
140 00
Country
Czechia
Facility Name
Inha University Hospital, Medicine/Rheumatology
City
Incheon
ZIP/Postal Code
400-711
Country
Korea, Republic of
Facility Name
Pusan National University Hospital, Rheumatology, Internal Medicine
City
Pusan
ZIP/Postal Code
602-739
Country
Korea, Republic of
Facility Name
Investigadores Clinicos Asociados
City
Mexico
State/Province
D.f.
ZIP/Postal Code
03300
Country
Mexico
Facility Name
Krakowskie Centrum Medyczne NZOZ
City
Krakow
ZIP/Postal Code
31-501
Country
Poland
Facility Name
Zaklad Reumatologii i Immunologii Klinicznej
City
Poznan
ZIP/Postal Code
60-356
Country
Poland
Facility Name
Oddzial Reumatologiczno-Rehabilitacyjny IIR Ortopedyczno-Rehabilitacyjny
City
Poznan
ZIP/Postal Code
61-545
Country
Poland
Facility Name
Hospital Nuestra Señora de La Esperanza
City
Santiago de Compostela
State/Province
A Coruña
ZIP/Postal Code
15705
Country
Spain
Facility Name
Complexo Hospitalario Universitario A Coruña
City
A Coruña
ZIP/Postal Code
15006
Country
Spain
Facility Name
Hospital General Universitario Gregorio Marañon
City
Madrid
ZIP/Postal Code
28007
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
22382341
Citation
Stock TC, Bloom BJ, Wei N, Ishaq S, Park W, Wang X, Gupta P, Mebus CA. Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate. J Rheumatol. 2012 Apr;39(4):720-7. doi: 10.3899/jrheum.110874. Epub 2012 Mar 1.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A6341009&StudyName=Study%20of%20CE-224%2C535%20A%20Twice%20Daily%20Pill%20To%20Control%20Rheumatoid%20Arthritis%20In%20Patients%20Who%20Have%20Not%20Totally%20Improved%20With%20Methotrexate
Description
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Study of CE-224,535 A Twice Daily Pill To Control Rheumatoid Arthritis In Patients Who Have Not Totally Improved With Methotrexate
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