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

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

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

Study Overview

• Status: Completed
• Conditions: Arthritis, Rheumatoid
• Intervention / Treatment: Drug: Placebo; Drug: CE-224,535

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 2

Contacts and Locations

Study Locations

• Chile
  • Santiago, RM
    • Providencia, Santiago, RM, Chile, 7530206
      • Clínica Santa María, Sección Reumatología
• Czechia
  • Ceska Lipa, Czechia, 470 01
    • Revmatologicka ambulance
  • Praha 2, Czechia, 128 50
    • Revmatologicky Ustav
  • Praha 4, Czechia, 140 00
    • Revmatologicka ambulance
• Korea, Republic of
  • Incheon, Korea, Republic of, 400-711
    • Inha University Hospital, Medicine/Rheumatology
  • Pusan, Korea, Republic of, 602-739
    • Pusan National University Hospital, Rheumatology, Internal Medicine
• Mexico
  • D.f.
    • Mexico, D.f., Mexico, 03300
      • Investigadores Clinicos Asociados
• Poland
  • Krakow, Poland, 31-501
    • Krakowskie Centrum Medyczne NZOZ
  • Poznan, Poland, 60-356
    • Zaklad Reumatologii i Immunologii Klinicznej
  • Poznan, Poland, 61-545
    • Oddzial Reumatologiczno-Rehabilitacyjny IIR Ortopedyczno-Rehabilitacyjny
• Spain
  • A Coruña, Spain, 15006
    • Complexo Hospitalario Universitario A Coruña
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • A Coruña
    • Santiago de Compostela, A Coruña, Spain, 15705
      • Hospital Nuestra Señora de La Esperanza
• United States
  • Arizona
    • Mesa, Arizona, United States, 85202
      • Arizona Arthritis & Rheumatology Associates, P.C.
  • Florida
    • DeBary, Florida, United States, 32713
      • Omega Research Consultants LLC
    • Lake Mary, Florida, United States, 32746
      • Florida Arthritis Center
    • Tampa, Florida, United States, 33614
      • Tampa Medical Group, PA
  • Indiana
    • Avon, Indiana, United States, 46123
      • American Health Network
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • George Stanley Walker, MD
    • New Orleans, Louisiana, United States, 70115
      • Best Clinical Trials, LLC (Administrative Only)
    • New Orleans, Louisiana, United States, 70115
      • Majid Abdul Jawad, MD
  • Maryland
    • Frederick, Maryland, United States, 21702
      • The Arthritis and Osteoporosis Center of Maryland
  • Missouri
    • Columbia, Missouri, United States, 65212
      • University of Missouri-Columbia
    • Columbia, Missouri, United States, 65203
      • University Physicians
  • Nevada
    • Reno, Nevada, United States, 89502
      • Arthritis Center of Reno
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • New Horizons Clinical Research
  • Washington
    • Spokane, Washington, United States, 99204-2336
      • Arthritis Northwest

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Active rheumatoid arthritis
• Incomplete response to methotrexate

Exclusion Criteria:

• Must not be on biologic therapies
• No recent infections

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; no active ingredient
Experimental: Active	Drug: CE-224,535; 500 mg po BID

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
CE-224,535 Plasma Concentrations	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]).	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

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• 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.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): April 7, 2008
• Primary Completion (Actual): February 4, 2009
• Study Completion (Actual): February 4, 2009

Study Registration Dates

• First Submitted: February 25, 2008
• First Submitted That Met QC Criteria: February 25, 2008
• First Posted (Estimate): March 4, 2008

Study Record Updates

• Last Update Posted (Actual): April 4, 2022
• Last Update Submitted That Met QC Criteria: March 9, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: rheumatoid arthritis DMARD methotrexate
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: A6341009; 2008-000327-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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.