Rheumatoid Arthritis Extension Trial For Subjects Who Have Participated In Other PF-05280586 Trials (REFLECTIONS B328-04)

EXTENSION STUDY EVALUATING TREATMENT WITH PF-05280586 VERSUS RITUXIMAB IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS WHO HAVE PARTICIPATED IN OTHER PF-05280586 CLINICAL TRIALS

This extension study will evaluate the safety (including immunogenicity) of treatment with rituximab-Pfizer, as well as the safety and immunogenicity after transitioning from rituximab-US or rituximab-EU to rituximab-Pfizer. This study will provide continued treatment access to subjects with active rheumatoid arthritis who have participated for at least 16 weeks in other studies in the rituximab Pfizer program.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: Rituximab-Pfizer (PF-05280586) x 3 courses; Biological: Rituximab-EU+ Rituximab-Pfizer x 2 Courses; Biological: Rituximab-US + Rituximab-Pfizer x 2 Courses

• Study Type: Interventional
• Enrollment (Actual): 185
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Maroochydore, Queensland, Australia, 4558
      • Rheumatology Research Unit
• Canada
  • Quebec, Canada, G1W 4R4
    • Centre de Recherche Saint-Louis
  • Quebec, Canada, G1V 3M7
    • Pharmacie Matte et Petit
  • Quebec
    • Rimouski, Quebec, Canada, G5L 8W1
      • Centre de Rhumatologie de l'Est du Quebec
    • Rimouski, Quebec, Canada, G5L 1J5
      • Clinique Medicale du Phare (ECG Only)
• Colombia
  • Antioquia
    • Medellin, Antioquia, Colombia
      • Rodrigo Botero S.A.S.
    • Medellin, Antioquia, Colombia
      • IPS Rodrigo Botero S.A.S.
    • Medellín, Antioquia, Colombia
      • Clínica Medellín S.A. Sede Centro
    • Medellín, Antioquia, Colombia
      • Mix Supplier S.A.
  • Atlantico
    • Barranquilla, Atlantico, Colombia
      • Centro de Reumatologia y Ortopedia
    • Barranquilla, Atlantico, Colombia
      • Clinica de la Costa Ltda.
    • Barranquilla, Atlantico, Colombia
      • Congregación de las Hermanas Franciscanas Misioneras de María Auxiliadora-Clinica La Asuncion
    • Barranquilla, Atlantico, Colombia
      • IPS Centro Integral de Reumatologia del Caribe, CIRCARIBE S.A.S.
    • Barranquilla, Atlantico, Colombia
      • IPS Centro Integral De Reumatologia del Caribe, CIRCARIBE S.A.S
    • Barranquilla, Atlantico, Colombia
      • Organizacion Clinica General del Norte S.A.
• Germany
  • Berlin, Germany, 14059
    • Schlosspark-Klinik GmbH, Internal Medicine II
• Israel
  • Tel Hashomer, Israel, 5262000
    • The Chaim Sheba Medical Center
• Mexico
  • San Luis Potosi, Mexico, 78213
    • Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi, S.C.
  • San Luis Potosi, Mexico, 78200
    • Hospital Angeles, Centro Medico del Potosi
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 06700
      • C.T. Scanner de Mexico, S.A. de C.V. (CT ONLY)
    • Mexico City, Distrito Federal, Mexico, 06700
      • CLIDITER, S.A de C.V.
    • Mexico City, Distrito Federal, Mexico, 06700
      • Hospital Angeles Clinica Londres
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 44650
      • Private office
    • Guadalajara, Jalisco, Mexico, 44200
      • Hospital Bernardette (Emergencies)
• Russian Federation
  • Kemerovo, Russian Federation, 650000
    • State Institution of Healthcare "Regional Clinical Hospital for Wars' Veterans"
  • Novosibirsk, Russian Federation, 630099
    • LLC Consulting and Diagnostic Rheumatological Center "Healthy Joints"
  • Samara, Russian Federation, 443095
    • State Budget Institution of Healthcare "Samara Regional Clinical Hospital named after V.D. Seredavin
  • Samara, Russian Federation, 443095
    • State Institution of Healthcare "Samara Regional Clinical Hospital named after V.D. Seredavin"
  • St Petersburg, Russian Federation, 191014
    • AVA-PETER Ltd.
  • St Petersburg, Russian Federation, 191025
    • Local Ethics Committee of LLC AVA-PETER
  • St. Petersburg, Russian Federation, 190068
    • St. Petersburg State Healthcare Institution "Clinical Rheumatology Hospital 25"
  • St. Petersburg, Russian Federation, 191014
    • "AVA-PETER" Ltd - Affiliate Address
  • St. Petersburg, Russian Federation
    • Laboratory of LLC AVA-PETER
  • Republic OF Tatarstan
    • Kazan, Republic OF Tatarstan, Russian Federation, 420103
      • LLC Scientific and Research Medical Complex "Your Health"
• South Africa
  • Cape Town, South Africa, 7500
    • Panorama Medical Centre - Room 136
  • KwaZulu Natal, South Africa, 3000
    • Dr. Jan Fourie Medical Centre
• United Kingdom
  • Leeds, United Kingdom, LS7 1NR
    • Division of Rheumatic & Musculoskeletal Diseases
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
    • Huntsville, Alabama, United States, 35801
      • Rheumatology Associates of North Alabama, PC
  • Arizona
    • Gilbert, Arizona, United States, 85234
      • Arthrocare, Arthritiscare & Research, PC
  • Arkansas
    • Hot Springs, Arkansas, United States, 71913
      • CHI St. Vincent Medical Group Hot Springs
  • California
    • Los Angeles, California, United States, 90095
      • UCLA david geffen school of medicine
    • Los Angeles, California, United States, 90095
      • UCLA Clinical & Translational Research Center
    • Palm Desert, California, United States, 92260
      • Desert Medical Advances
  • Connecticut
    • Trumbull, Connecticut, United States, 06611
      • New England Research Associates, LLC
  • Delaware
    • Newark, Delaware, United States, 19711
      • QPS Labs
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida - College of Medicine Carol and Frank Morsani Center
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
    • Morton Grove, Illinois, United States, 60053
      • Illnois Bone & Joint Institute
  • Indiana
    • Indianapolis, Indiana, United States, 46214
      • Covance Central Laboratory Services
  • Kentucky
    • Lexington, Kentucky, United States, 40504
      • Bluegrass Community Research, Inc.
  • Maryland
    • Cumberland, Maryland, United States, 21502
      • Klein & Associates, M.D., P.A.
  • Massachusetts
    • Worcester, Massachusetts, United States, 01605
      • Clinical Pharmacology Study Group
  • Michigan
    • Battle Creek, Michigan, United States, 49015
      • Bronson Internal Medicine and Rheumatology
    • Lansing, Michigan, United States, 48910
      • Justus J. Fiechtner, MD, PC
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University of Nevada School of Medicine
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth - Hitchcock Medical Center
  • New York
    • Great Neck, New York, United States, 11021
      • North Shore-LIJ Health System - Division of Rheumatology and Allergy-Clinical
  • North Carolina
    • Hickory, North Carolina, United States, 28602
      • PMG Research of Hickory LLC
    • Hickory, North Carolina, United States, 28602
      • PMG Research of Hickory, LLC
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Cincinnati Rheumatic Disease Study Group
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73103
      • Health Research of Oklahoma
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center For Clinical Research
    • Philadelphia, Pennsylvania, United States, 19152
      • The Arthritis Group
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading, LLC
  • Tennessee
    • Hixson, Tennessee, United States, 37343
      • Arthritis Associates, PLLC
    • Jackson, Tennessee, United States, 38305
      • Arthritis Clinic
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
  • Texas
    • Dallas, Texas, United States, 75231
      • Metroplex Clinical Research Center
    • Houston, Texas, United States, 77054
      • Apocell, Inc
    • Mesquite, Texas, United States, 75150
      • Southwest Rheumatology Research, LLC

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
• Participated for a minimum of 16 weeks after the initiation of the last course of treatment in a previous rheumatoid arthritis study in the rituximab-Pfizer program within the past 2 months.

Exclusion Criteria:

• Investigational site staff members or relatives of those site staff members or subjects who are Pfizer employees directly involved in the conduct of the study.
• Initiated treatment with investigational agents or other biologics (including Rituxan and MabThera) since participating in a previous rheumatoid arthritis study in the rituximab-Pfizer program.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rituximab-Pfizer	Biological: Rituximab-Pfizer (PF-05280586) x 3 courses; 1000 mg intravenous infusion [IV] on Days 1 and 15 of each 24 week treatment course for up to 3 treatment courses
Active Comparator: Rituximab-EU+Rituximab-Pfizer; Subjects will receive Rituximab-EU x 1 course followed by Rituximab-Pfizer x 2 courses.	Biological: Rituximab-EU+ Rituximab-Pfizer x 2 Courses; Subjects will receive Rituximab-EU x 1 course followed by Rituximab-Pfizer x 2 courses. 1000 mg IV infusion of Rituximab-EU on Days 1 and 15 of a 24 week treatment course followed by 1000 mg IV infusion of PF-05280586 on Days 1 and 15 of each 24 week course for up to 2 additional treatment courses
Active Comparator: Rituximab-US+Rituximab-Pfizer; Subjects will receive Rituximab-US x 1 course followed by Rituximab-Pfizer x 2 courses.	Biological: Rituximab-US + Rituximab-Pfizer x 2 Courses; Subjects will receive Rituximab-US x 1 course followed by Rituximab-Pfizer x 2 courses. 1000 mg IV infusion of Rituximab-US on Days 1 and 15 of a 24 week treatment course followed by 1000 mg IV infusion of PF-05280586 on Days 1 and 15 of each 24 week course for up to 2 additional treatment courses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants by Anti-Drug Antibody (ADA) Status Using Anti-PF-05280586 Antibody Assay	Serum samples were collected to determine the presence of ADA using two validated assays, one specific for PF-05280586 and one specific for the licensed drug products. For participants assigned to PF-05280586 in Study B3281001, blood samples were screened for ADA using the assay specific to PF-05280586; if the blood samples were confirmed to be positive (+ve) for ADA against PF-05280586, the samples were also analyzed using the assay specific for the licensed drug products to assess cross-reactivity of the ADA. For participants assigned to the licensed products in Study B3281001, blood samples were screened for ADA using both assays in order to assess any product-specific ADA and/or cross-reactivity for the transition from the licensed products to PF-05280586.	Course 1 (C1) Overall, Course 2 (C2) Overall, Course 3 (C3) Overall, and All Courses Overall.
Percentage of Participants by ADA Status Using Anti-Rituximab Antibody Assay	Serum samples were collected to determine the presence of ADA using two validated assays, one specific for PF-05280586 and one specific for the licensed drug products. For participants assigned to PF-05280586 in Study B3281001, blood samples were screened for ADA using the assay specific to PF-05280586; if the blood samples were confirmed to be positive for ADA against PF-05280586, the samples were also analyzed using the assay specific for the licensed drug products to assess cross-reactivity of the ADA. For participants assigned to the licensed products in Study B3281001, blood samples were screened for ADA using both assays in order to assess any product-specific ADA and/or cross-reactivity for the transition from the licensed products to PF-05280586.	Course 1 Overall, Course 2 Overall, Course 3 Overall, and All Courses Overall.
Percentage of Participants by Neutralizing Antibody (Nab) Status in Participants With a Positive ADA Using Anti-PF-05280586 NAb Assay	Blood samples that were confirmed as positive for ADA were further evaluated for Nab using validated assays - None of the ADA samples tested positive for NAb.	Weeks 1, 3, 13, and 25 (Course 1, Course 2, and Course 3).
Percentage of Participants by Nab Status in Participants With a Positive ADA Using Anti-PF-05280586 NAb Assay Using Anti-Rituximab NAb Assay	Blood samples that were confirmed as positive for ADA were further evaluated for Nab using validated assays. - None of the ADA samples tested positive for NAb.	Weeks 1, 3, 13, and 25 (Course 1, Course 2, and Course 3).
Mean Rituximab Serum Trough Concentrations	Serum samples for determination of drug concentrations were collected pre-dose concurrent with ADA sample collection. Drug concentrations in the samples were determined using a validated assay.	Weeks 1, 3, 13, and 25 (Course 1, Course 2, and Course 3), Follow up Months 3, 6, 9, and 12. Course 3/Week 25 is End of Treatment (EOT).
Cluster of Differentiation 19 (CD19+) B Cell Count	Blood samples were assayed for CD19+ B-cell counts using laser scanning cytometry.	Weeks 1, 6, 13, and 25 (Course 1 and Course 2), Weeks 1, 13, 25 (Course 3), and Follow up Months 3, 6, and 9.
Circulating Immunoglobulin G (IgG) Concentrations	Blood samples for immunoglobulin assessments were obtained to determine IgG levels in serum.	Screening, Week 25 (Course 1), and Weeks 1 and 25 (Course 2 and Course 3).
Circulating Immunoglobulin M (IgM) Concentrations	Blood samples for immunoglobulin assessments were obtained to determine IgM levels in serum.	Screening, Week 25 (Course 1), and Weeks 1 and 25 (Course 2 and Course 3).
Circulating Rheumatoid Factor (RF) Concentrations	RF is the auto-antibody directed against IgG. Blood samples were obtained to determine RF levels in serum.	Week 1 and 25 (Course 1, Course 2, and Course 3).
Anti-Cyclic Citrullinated Peptide (Anti-CCP) and Complement	Blood samples were obtained to determine anti-CCP and compliment levels in serum.	Week 1 and 25 (Course 1, Course 2, and Course 3).
Mean Change From Initial Study Baseline in Disease Activity Score (DAS28)-C-Reactive Protein (CRP) - by the End of Course 1	The disease activity score (DAS) assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis Visual Analog Scale (VAS). The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP equals (=) 0.56 square root (sqrt) (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 natural log [ln] (CRP [milligrams per liter, mg/L] +1) + 0.014 (global assessment of health [GH]) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity.	Baseline B3281001, Week 1, 6, 13, and 25 (Course 1).
Mean Change From Initial Study Baseline in Disease Activity Score (DAS28)-C-Reactive Protein (CRP) - by the End of Course 2	The disease activity score (DAS) assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis Visual Analog Scale (VAS). The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP equals (=) 0.56 square root (sqrt) (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 natural log [ln] (CRP [milligrams per liter, mg/L] +1) + 0.014 (global assessment of health [GH]) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity.	Baseline B3281001, Week 1, 6, 13, and 25 (Course 1 and Course 2).
Mean Change From Initial Study Baseline in Disease Activity Score (DAS28)-C-Reactive Protein (CRP) - by the End of Course 3	The disease activity score (DAS) assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis Visual Analog Scale (VAS). The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP equals (=) 0.56 square root (sqrt) (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 natural log [ln] (CRP [milligrams per liter, mg/L] +1) + 0.014 (global assessment of health [GH]) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity.	Baseline B3281001, Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on DAS28 - by the End of Course 1	The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with present DAS28 less than or equal to (≤) 3.2; moderate responders had a change from baseline >0.6 and ≤1.2 with present DAS28 ≤3.2 or change from baseline >0.6 with present DAS28 >3.2 and ≤5.1 or change from baseline >1.2 with present DAS28 >5.1; non-responders had a change from baseline ≤0.6 with present DAS28 ≤5.1 or change from baseline ≤1.2 with present DAS28 >5.1.	Week 1, 6, 13, and 25 (Course 1).
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on DAS28 - by the End of Course 2	The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with present DAS28 less than or equal to (≤) 3.2; moderate responders had a change from baseline >0.6 and ≤1.2 with present DAS28 ≤3.2 or change from baseline >0.6 with present DAS28 >3.2 and ≤5.1 or change from baseline >1.2 with present DAS28 >5.1; non-responders had a change from baseline ≤0.6 with present DAS28 ≤5.1 or change from baseline ≤1.2 with present DAS28 >5.1.	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on DAS28 - by the End of Course 3	The DAS28-based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders had a change from baseline greater than (>) 1.2 with present DAS28 less than or equal to (≤) 3.2; moderate responders had a change from baseline >0.6 and ≤1.2 with present DAS28 ≤3.2 or change from baseline >0.6 with present DAS28 >3.2 and ≤5.1 or change from baseline >1.2 with present DAS28 >5.1; non-responders had a change from baseline ≤0.6 with present DAS28 ≤5.1 or change from baseline ≤1.2 with present DAS28 >5.1.	Week 1, 6, 13, and 25 (Course 1 and Course 2) and Week 1, 13, and 25 (Course 3).
Percentage of Participants With Low Disease Activity State (LDAS) (≤3.2) - by the End of Course 1	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity.	Week 1, 6, 13, and 25 (Course 1).
Percentage of Participants With Low Disease Activity State (LDAS) (≤3.2) - by the End of Course 2	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity.	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percentage of Participants With Low Disease Activity State (LDAS) (≤3.2) - by the End of Course 3	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP ≤3.2 implied low disease activity.	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Percentage of Participants With DAS Remission (DAS28-CRP Less Than [<] 2.6) - by the End of Course 1	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP <2.6 implied remission.	Week 1, 6, 13, and 25 (Course 1).
Percentage of Participants With DAS Remission (DAS28-CRP Less Than [<] 2.6) - by the End of Course 2	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP <2.6 implied remission.	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percentage of Participants With DAS Remission (DAS28-CRP Less Than [<] 2.6) - by the End of Course 3	The DAS assessment is a continuous composite measure derived using differential weighting given to the following 4 components: tender/painful joint count (28 joints), swollen joint count (28 joints), CRP and patient's global assessment of arthritis VAS. The formula for calculation of DAS28-CRP from these 4 components is DAS28-CRP = 0.56 sqrt (DAS 28 tender joint count) + 0.28 sqrt (DAS 28 swollen joint count) + 0.36 (ln CRP [mg/L] +1) + 0.014 (GH) + 0.96. Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP <2.6 implied remission.	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response - by the End of Course 1	ACR20 response: ≥ 20 percent (%) improvement in tender/painful joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CRP.	Week 1, 6, 13, and 25 (Course 1).
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response - by the End of Course 2	ACR20 response: ≥ 20 percent (%) improvement in tender/painful joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CRP.	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response - by the End of Course 3	ACR20 response: ≥ 20 percent (%) improvement in tender/painful joint count; ≥ 20% improvement in swollen joint count; and ≥ 20% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ]); and CRP.	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Percentage of Participants With American College of Rheumatology (ACR) 50% Improvement (ACR50) Response - by the End of Course 1	ACR50 response: ≥50% improvement in tender/painful joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.	Week 1, 6, 13, and 25 (Course 1).
Percentage of Participants With American College of Rheumatology (ACR) 50% Improvement (ACR50) Response - by the End of Course 2	ACR50 response: ≥50% improvement in tender/painful joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percentage of Participants With American College of Rheumatology (ACR) 50% Improvement (ACR50) Response - by the End of Course 3	ACR50 response: ≥50% improvement in tender/painful joint count; ≥50% improvement in swollen joint count; and ≥50% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Percentage of Participants With American College of Rheumatology (ACR) 70% Improvement (ACR70) Response - by the End of Course 1	ACR70 response: ≥70% improvement in tender/painful joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.	Week 1, 6, 13, and 25 (Course 1).
Percentage of Participants With American College of Rheumatology (ACR) 70% Improvement (ACR70) Response - by the End of Course 2	ACR70 response: ≥70% improvement in tender/painful joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percentage of Participants With American College of Rheumatology (ACR) 70% Improvement (ACR70) Response - by the End of Course 3	ACR70 response: ≥70% improvement in tender/painful joint count; ≥70% improvement in swollen joint count; and ≥70% improvement in at least 3 of 5 remaining ACR core measures: participant assessment of arthritis pain; participant global assessment of arthritis; physician global assessment of arthritis; self-assessed disability (disability index of the HAQ); and CRP.	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Tender/Painful Joint Count - by the End of Course 1	Sixty-eight joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.	Screening, Week 1, 6, 13, and 25 (Course 1).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Tender/Painful Joint Count - by the End of Course 2	Sixty-eight joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.	Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Tender/Painful Joint Count - by the End of Course 3	Sixty-eight joints were assessed by a blinded joint assessor to determine the number of joints that were considered tender or painful. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response to pressure/motion on each joint was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.	Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2), and Screening, Week 1, 13, and 25 (Course 3).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Swollen Joint Count - by the End of Course 1	Sixty-six joints were assessed by a blinded joint assessor for swelling. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.	Screening, Week 1, 6, 13, and 25 (Course 1).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Swollen Joint Count - by the End of Course 2	Sixty-six joints were assessed by a blinded joint assessor for swelling. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.	Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Swollen Joint Count - by the End of Course 3	Sixty-six joints were assessed by a blinded joint assessor for swelling. For consistency, a single assessor was preferred to perform all evaluations across the study for an individual participant. The response was assessed using the following scale: Present/Absent/Not Done/Not Applicable (to be used for artificial or missing joints). Artificial joints were not be assessed.	Screening, Week 1, 6, 13, and 25 (Course 1 and Course 2), and Screening, Week 1, 13, and 25 (Course 3).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Assessment of Arthritis Pain - by the End of Course 1	Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.	Week 1, 6, 13, and 25 (Course 1).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Assessment of Arthritis Pain - by the End of Course 2	Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Assessment of Arthritis Pain - by the End of Course 3	Participants assessed the severity of their arthritis pain using a 100 millimeter (mm) VAS by placing a mark on the scale between 0 (no pain) and 100 (most severe pain), which corresponded to the magnitude of their pain.	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Global Assessment of Arthritis - by the End of Course 1	Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" Their response was recorded using a 100 mm VAS between 0 (very well) and 100 (very poor).	Week 1, 6, 13, and 25 (Course 1).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Global Assessment of Arthritis - by the End of Course 2	Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" Their response was recorded using a 100 mm VAS between 0 (very well) and 100 (very poor).	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Patient's Global Assessment of Arthritis - by the End of Course 3	Participants were asked the following question, "Considering all the ways your arthritis affects you, how are you feeling today?" Their response was recorded using a 100 mm VAS between 0 (very well) and 100 (very poor).	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Physician's Global Assessment of Arthritis - by the End of Course 1	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (very good) and 100 (very poor).	Week 1, 6, 13, and 25 (Course 1).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Physician's Global Assessment of Arthritis - by the End of Course 2	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (very good) and 100 (very poor).	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Physician's Global Assessment of Arthritis - by the End of Course 3	The investigator assessed how the participant's overall arthritis appeared at the time of the visit. This evaluation was based on the participant's disease signs, functional capacity and physical examination, and was independent of the Patient's Global Assessment of Arthritis. The investigator's response was recorded using a 100 mm VAS by placing a mark on the scale between 0 (very good) and 100 (very poor).	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Health Assessment Questionnaire - Disability Index (HAQ-DI) - by the End of Course 1	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcomes reported post baseline mean percent (%) changes in HAQ-DI score. Post baseline values are reported on the % change from initial study Baseline scale.	Week 1, 6, 13, and 25 (Course 1).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Health Assessment Questionnaire - Disability Index (HAQ-DI) - by the End of Course 2	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcomes reported post baseline mean percent (%) changes in HAQ-DI score. Post baseline values are reported on the % change from initial study Baseline scale.	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Percent Change From Initial Study Baseline in Individual Components of the ACR Response: Health Assessment Questionnaire - Disability Index (HAQ-DI) - by the End of Course 3	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcomes reported post baseline mean percent (%) changes in HAQ-DI score. Post baseline values are reported on the % change from initial study Baseline scale.	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).
Outcome Measure Using HAQ-DI - by the End of Course 1	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcome reported in the table is mean HAQ-DI score at each time point, and it is on the scale of HAQ-DI score with the range from 0 to 3.	Week 1, 6, 13, and 25 (Course 1).
Outcome Measure Using HAQ-DI - by the End of Course 2	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcome reported in the table is mean HAQ-DI score at each time point, and it is on the scale of HAQ-DI score with the range from 0 to 3.	Week 1, 6, 13, and 25 (Course 1 and Course 2).
Outcome Measure Using HAQ-DI - by the End of Course 3	HAQ-DI assessed the degree of difficulty participants experienced in 8 daily living activity domains during a week: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other activities. Each activity category consisted of 2-3 items. Each question's difficulty was scored from 0-3 (0=no difficulty, 1=some difficulty, 2=much difficulty, 3=unable to do). Activities requiring assistance (from people or assistive devices) were adjusted to ≥2 to denote more limited functional status. The questionnaire was to be completed by the participant prior to any procedures during the visit, if possible. Overall HAQ-DI score was computed as the sum of domain scores divided by the number of domains answered, providing a score from 0-3. Low scores denoted improvement of disability/lower degree of domain difficulty. Primary outcome reported in the table is mean HAQ-DI score at each time point, and it is on the scale of HAQ-DI score with the range from 0 to 3.	Week 1, 6, 13, and 25 (Course 1 and Course 2), and Week 1, 13, and 25 (Course 3).

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Cohen SB, Burgos-Vargas R, Emery P, Jin B, Cronenberger C, Vazquez-Abad MD. Extension Study of PF-05280586, a Potential Rituximab Biosimilar, Versus Rituximab in Subjects With Active Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2018 Nov;70(11):1598-1606. doi: 10.1002/acr.23586.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 16, 2012
• Primary Completion (Actual): March 14, 2016
• Study Completion (Actual): March 14, 2016

Study Registration Dates

• First Submitted: July 6, 2012
• First Submitted That Met QC Criteria: July 16, 2012
• First Posted (Estimate): July 18, 2012

Study Record Updates

• Last Update Posted (Actual): January 29, 2019
• Last Update Submitted That Met QC Criteria: January 8, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; rituximab; extension trial
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: B3281004; ICON 9002/0101; 2012-003223-38 (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.