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

Rheumatoid Arthritis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01643928
• Other study ID #: B3281004
• Secondary ID: ICON 9002/010120
• Status: Completed
• Phase: N/A
• Start date: August 16, 2012
• Est. completion date: March 14, 2016

Study information

• Verified date: January 2019
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 185
• Est. completion date: March 14, 2016
• Est. primary completion date: March 14, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Australia	Rheumatology Research Unit	Maroochydore	Queensland
Canada	Centre de Recherche Saint-Louis	Quebec
Canada	Pharmacie Matte et Petit	Quebec
Canada	Centre de Rhumatologie de l'Est du Quebec	Rimouski	Quebec
Canada	Clinique Medicale du Phare (ECG Only)	Rimouski	Quebec
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.	Barranquilla	Atlantico
Colombia	IPS Rodrigo Botero S.A.S.	Medellin	Antioquia
Colombia	Rodrigo Botero S.A.S.	Medellin	Antioquia
Colombia	Clínica Medellín S.A. Sede Centro	Medellín	Antioquia
Colombia	Mix Supplier S.A.	Medellín	Antioquia
Germany	Schlosspark-Klinik GmbH, Internal Medicine II	Berlin
Israel	The Chaim Sheba Medical Center	Tel Hashomer
Mexico	Hospital Bernardette (Emergencies)	Guadalajara	Jalisco
Mexico	Private Office	Guadalajara	Jalisco
Mexico	C.T. Scanner de Mexico, S.A. de C.V. (CT ONLY)	Mexico City	Distrito Federal
Mexico	CLIDITER, S.A de C.V.	Mexico City	Distrito Federal
Mexico	Hospital Angeles Clinica Londres	Mexico City	Distrito Federal
Mexico	Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi, S.C.	San Luis Potosi
Mexico	Hospital Angeles, Centro Medico del Potosi	San Luis Potosi
Russian Federation	LLC Scientific and Research Medical Complex "Your Health"	Kazan	Republic OF Tatarstan
Russian Federation	State Institution of Healthcare "Regional Clinical Hospital for Wars' Veterans"	Kemerovo
Russian Federation	LLC Consulting and Diagnostic Rheumatological Center "Healthy Joints"	Novosibirsk
Russian Federation	State Budget Institution of Healthcare "Samara Regional Clinical Hospital named after V.D. Seredavin	Samara
Russian Federation	State Institution of Healthcare "Samara Regional Clinical Hospital named after V.D. Seredavin"	Samara
Russian Federation	AVA-PETER Ltd.	St Petersburg
Russian Federation	Local Ethics Committee of LLC AVA-PETER	St Petersburg
Russian Federation	"AVA-PETER" Ltd - Affiliate Address	St. Petersburg
Russian Federation	Laboratory of LLC AVA-PETER	St. Petersburg
Russian Federation	St. Petersburg State Healthcare Institution "Clinical Rheumatology Hospital 25"	St. Petersburg
South Africa	Panorama Medical Centre - Room 136	Cape Town
South Africa	Dr. Jan Fourie Medical Centre	KwaZulu Natal
United Kingdom	Division of Rheumatic & Musculoskeletal Diseases	Leeds
United States	Bronson Internal Medicine and Rheumatology	Battle Creek	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Cincinnati Rheumatic Disease Study Group	Cincinnati	Ohio
United States	Klein & Associates, M.D., P.A.	Cumberland	Maryland
United States	Metroplex Clinical Research Center	Dallas	Texas
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Arthrocare, Arthritiscare & Research, PC	Gilbert	Arizona
United States	North Shore-LIJ Health System - Division of Rheumatology and Allergy-Clinical	Great Neck	New York
United States	PMG Research of Hickory LLC	Hickory	North Carolina
United States	PMG Research of Hickory, LLC	Hickory	North Carolina
United States	Arthritis Associates, PLLC	Hixson	Tennessee
United States	CHI St. Vincent Medical Group Hot Springs	Hot Springs	Arkansas
United States	Apocell, Inc	Houston	Texas
United States	Rheumatology Associates of North Alabama, PC	Huntsville	Alabama
United States	Covance Central Laboratory Services	Indianapolis	Indiana
United States	Arthritis Clinic	Jackson	Tennessee
United States	West Tennessee Research Institute	Jackson	Tennessee
United States	Justus J. Fiechtner, MD, PC	Lansing	Michigan
United States	University of Nevada School of Medicine	Las Vegas	Nevada
United States	Dartmouth - Hitchcock Medical Center	Lebanon	New Hampshire
United States	Bluegrass Community Research, Inc.	Lexington	Kentucky
United States	UCLA Clinical & Translational Research Center	Los Angeles	California
United States	UCLA David Geffen School of Medicine	Los Angeles	California
United States	Loyola University Medical Center	Maywood	Illinois
United States	Southwest Rheumatology Research, LLC	Mesquite	Texas
United States	Illnois Bone & Joint Institute	Morton Grove	Illinois
United States	QPS Labs	Newark	Delaware
United States	Health Research of Oklahoma	Oklahoma City	Oklahoma
United States	Desert Medical Advances	Palm Desert	California
United States	The Arthritis Group	Philadelphia	Pennsylvania
United States	University of South Florida - College of Medicine Carol and Frank Morsani Center	Tampa	Florida
United States	New England Research Associates, LLC	Trumbull	Connecticut
United States	Clinical Pharmacology Study Group	Worcester	Massachusetts
United States	Clinical Research Center of Reading, LLC	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Colombia,  Germany,  Israel,  Mexico,  Russian Federation,  South Africa,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	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.
Primary	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).
Primary	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).
Primary	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).
Primary	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.
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).
Primary	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).

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