Rheumatoid Arthritis Clinical Trial
— REFLECTIONSOfficial title:
A RANDOMIZED, DOUBLE-BLIND, STUDY COMPARING THE PHARMACOKINETICS AND PHARMACODYNAMICS, AND ASSESSING THE SAFETY OF PF-05280586 AND RITUXIMAB IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS ON A BACKGROUND OF METHOTREXATE WHO HAVE HAD AN INADEQUATE RESPONSE TO ONE OR MORE TNF ANTAGONIST THERAPIES
Verified date | October 2019 |
Source | Pfizer |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
In this study, patients with moderate to severe rheumatoid arthritis who are being treated with methotrexate will receive 2 intravenous treatments with either PF-05280586 or Rituxan (Rituximab) or MabThera (Rituximab). During the course of the study, the effects of the drugs will be assessed by sampling the levels of drug in the blood, blood cell counts, and by comparing these levels among the different treatments. Safety, tolerability and immunologic response also will be evaluated throughout.
Status | Completed |
Enrollment | 220 |
Est. completion date | May 7, 2014 |
Est. primary completion date | August 13, 2013 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: - Confirmed diagnosis of rheumatoid arthritis - Meets Class I, II or III of the ACR 1991 Revised Criteria - RA seropositivity - Stable dose of methotrexate - Inadequate response to TNF inhibitors Exclusion Criteria: - Any prior treatment with lymphocyte depleting therapies - History of active TB infection - Known or screen test positive for specific viruses or indicators of viral infection |
Country | Name | City | State |
---|---|---|---|
Australia | St. Vincent's Hospital (Melbourne) | Fitzroy | Victoria |
Australia | Rheumatology Research Unit | Maroochydore | Queensland |
Australia | The Queen Elizabeth Hospital, Department of Rheumatology | Woodville South | South Australia |
Canada | Centre de Rhumatologie St-Louis | Quebec | |
Canada | Pharmacie Matte et Petit | Quebec | |
Canada | Centre de Rhumatologie de l'Est du Quebec | Rimouski | Quebec |
Canada | Clinique Medicale du Phare | Rimouski | Quebec |
Canada | Centre de Recherche Musculo-Squelettique | Trois-Rivieres | Quebec |
Colombia | Cediul S.A. | Barranquilla | Atlantico |
Colombia | Centro de Reumatologia y Ortopedia | Barranquilla | Atlántico |
Colombia | Clinica Bonnadona - Prevenir S.A. | Barranquilla | Atlantico |
Colombia | Clinica de la Costa Ltdz. | Barranquilla | Atlantico |
Colombia | IPS Centro Integral de Reumatologia del Cairbe, CIRCARIBE S.A.S. | Barranquilla | Atlantico |
Colombia | Sabbag Radiologos Ltda. | Barranquilla | Atlantico |
Colombia | Cerid S.A. | Barranquilla, Colombia | Atlántico |
Colombia | Congregacion de las Hemanas Franciscanas Misioneras de Maria Auxiliadora - Clinica La Asuncion | Barranquilla, Colombia | Atlántico |
Colombia | IPS Clinica General del Norte S.A. | Barranquilla, Colombia | Atlántico |
Colombia | Clinica Medellin S.A Sede Centro | Medellin | Antioquia |
Colombia | Mix Supplier S.A | Medellin | Antioquia |
Colombia | Rodrigo Botero S.A.S. | Medellin | Antioquia |
Germany | Schlosspark-Klinik GMBH, Internal Medicine II | Berlin | |
Israel | The Chaim Sheba Medical Center Department of Internal Medicine B | Ramat Gan | |
Mexico | Centro De Investigacion Y Atencion Integral Durango CIAID | Durango | |
Mexico | Private Office | Guadalajara | Jalisco |
Mexico | Cliditer, S.A. de C.V. | Mexico | D.f. |
Mexico | Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C. | San Luis Potosi | |
Russian Federation | GBUZ City Clinical Hospital #7 | Kazan | Tatarstan |
Russian Federation | State Institution of Healthcare "Regional Clinical Hospital for Wars' Veterans" | Kemerovo | |
Russian Federation | State Budgetary Institution of Healthcare of Nizhegorodskiy Region | Nizhny Novgorod | |
Russian Federation | LLC CDCR "Healthy Joints" | Novosibirsk | Novosibirsk Region |
Russian Federation | St. Petersburg state Healthcare lnstitution 'Clinical Rheumatology Hospital No25 | Saint-Petersburg | |
Russian Federation | State Institute of Healthcare Samara Regional Clinical Hospital named after M.I.Kalinin | Samara | |
Russian Federation | Llc Ava-Peter | St. Petersburg | |
Russian Federation | Regional State Budget Institution of Healthcare "Tomsk Regional Clinical Hospital" | Tomsk | |
South Africa | Dr. Jan Fourie Medical Centre | Dundee | Kwa-zulu Natal |
South Africa | Panorama Medical Centre | Panorama | Cape Town |
United Kingdom | "The University of Leeds, | Leeds | |
United Kingdom | Bexley Wing - St. James's University Hospital | Leeds | UK |
United Kingdom | Pharmacy Department, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust | Leeds | |
United Kingdom | Pharmacy Dispensing - Bexley Wing - St. James's University Hospital | Leeds | |
United Kingdom | Whipps Cross University Hospital | London | |
United States | Bronson Internal Medicine & Rheumatology | Battle Creek | Michigan |
United States | University of Alabama at Bermingham | Birmingham | Alabama |
United States | University of Alabama at Birmingham - Arthritis Clinical Intervention Program (ACIP) SRC 076 | Birmingham | Alabama |
United States | Loyola Center for Health at Burr Ridge | Burr Ridge | Illinois |
United States | Box Arthritis & Rheumatology of the Carolinas, PLLC | Charlotte | North Carolina |
United States | Cincinnati Rheumatic Disease Study Group, Inc. | 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, Arthritis Care & Research, PC | Gilbert | Arizona |
United States | North Shore-LIJ Health System - Division of Rheumatology and Allergy-Clinical Immunology | Great Neck | New York |
United States | Klein & Associates, M.D., P.A. | Hagerstown | Maryland |
United States | Hickory Family Practice Associates | Hickory | North Carolina |
United States | PMG Research of Hickory | Hickory | North Carolina |
United States | PMG Research of Hickory, LLC - PI's Main Office (Subject visit, IP Storage, Infusion, & Lab Draws) | Hickory | North Carolina |
United States | Arthritis Associates, PLLC | Hixson | Tennessee |
United States | Mercy Clinic Hot Springs Communities | Hot Springs | Arkansas |
United States | Center For Clinical Trials Of Houston | Houston | Texas |
United States | Rheumatology Associates of North Alabama, PC | Huntsville | Alabama |
United States | Arthritis Clinic | Jackson | Tennessee |
United States | West Tennessee Research Institute | Jackson | Tennessee |
United States | Rheumatology/Arthritis Center | 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 | Ronald Reagan UCLA Medical Center | Los Angeles | California |
United States | UCLA David Geffen School of Medicine | Los Angeles | California |
United States | Loyola Medical Medical Center Outpatient Center | Maywood | Illinois |
United States | Loyola University Medical Center Pharmacy | Maywood | Illinois |
United States | Southwest Rheumatology Research LLC. | Mesquite | Texas |
United States | Illinois Bone and Joint Institute | Morton Grove | Illinois |
United States | Loyola Center for health at Oakbrook Terrace North | Oakbrook Terrace | Illinois |
United States | Health Research of Oklahoma | Oklahoma City | Oklahoma |
United States | Arthritis Associates | Orlando | Florida |
United States | Desert Medical Advances | Palm Desert | California |
United States | The Arthritis Group | Philadelphia | Pennsylvania |
United States | Advances In Medicine | Rancho Mirage | California |
United States | University of South Florida - College of Medicine, Frank and Carol Morsani Center | Tampa | Florida |
United States | New England Research Assoc. LLC | Trumbull | Connecticut |
United States | Clinical Pharmacology Study Group | Worcester | Massachusetts |
United States | UMass Memorial Medical Center - Memorial Campus | Worcester | Massachusetts |
United States | UMass Memorial Medical Center-Rheumatology Center-Memorial Campus | Worcester | Massachusetts |
United States | Clinical Research Center of Reading, LLP | Wyomissing | Pennsylvania |
Lead Sponsor | Collaborator |
---|---|
Pfizer |
United States, Australia, Canada, Colombia, Germany, Israel, Mexico, Russian Federation, South Africa, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Maximum Serum Concentration (Cmax) of Rituximab | Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered. | Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion | |
Primary | AUC 0-inf of Rituximab | The AUC 0-inf refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) extrapolated to infinity. | Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion | |
Secondary | Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk) | The AUC 0-2wk refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to 2 weeks after drug administration. | Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion | |
Secondary | Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T) | The AUC 0-T refers to the concentration in serum of the drug over time. It represents the total drug exposure over time, from time 0 (the point of drug administration) to the last measured concentration at time T. | Predose (Day 1) and 3, 4.25 (immediately before 1st infusion end), 72, 168, 335 (Day 15 within 1.5 hours before 2nd infusion), 337.5, 339.25 (Day 15 immediately before 2nd infusion end), 408, 504, 672, 1344, and 2016 hours after start of 1st infusion | |
Secondary | CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell) | The AUC 0-T,B-cell refers to the concentration in serum of B-cells. It represents the total B-cells over time from time 0 (the point of drug administration) to the last measurement taken at time T. | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | |
Secondary | Minimum Post-Baseline CD19+ B-cell Count (/uL) | The lowest CD19+ B-cell count measured in a participant's blood post-baseline. | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | |
Secondary | Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks) | The amount of time in weeks from baseline to the lowest observed CD19+ B-cell count. | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | |
Secondary | Duration of B-cell Depletion (tB-cell) (Days) | The tB-cell is defined as the time interval over which the B-cell count was <0.3 cells/uL or the detection limit. | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | |
Secondary | Percentage of Participants With CD19+ B-cell Count Recovery | The percentage of participants with CD19+ B-cell counts which fell to <50% of Baseline value during treatment and which recovered to =50% of Baseline value at End of Treatment. | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell) | The AUC 0-T, B-cell refers to the CD19+ B-cell count over time. It represents the total B-cells over time, from time 0 (the point of drug administration) to the last measured count at time T. | Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT) | |
Secondary | Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L]) | The level of IgM in serum at Baseline and the change from Baseline at each subsequent visit. | Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 (EOT) | |
Secondary | Percent (%) Change From Baseline in Circulating IgM by Visit (g/L) | The percentage change from Baseline in circulating IgM by visit. | Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit | ACR20 response: greater than or equal to (=)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). Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on. |
Weeks 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit | ACR70 response: =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 HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participantss who rolled over to the extension study were not included in the non-responder imputation from that point on. |
Weeks 3, 5, 9, 13, 17, 21 and 25 (EOT) | |
Secondary | Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit | ACR50 response: =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 HAQ); and CRP. Non-responder imputation categorized participants as having a non-response if they did not have data available at a visit due to missing data or study discontinuation. Participants who rolled over to the extension study were not included in the non-responder imputation from that point on. |
Weeks 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percentage of Participants by Anti-drug Antibody (ADA) Status | Presence of anti-rituximab antibodies in blood. Participants with a positive antibody status at any time during the study were defined as having overall positive antibody status; participants with a negative antibody status throughout the study were defined as having overall negative antibody status. | Days 1 up to Day 169. | |
Secondary | Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit | Day 1 up to Day 169 | ||
Secondary | Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP) | DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (=)3.2 implied low disease activity, DAS28-CRP greater than (>)3.2 to =5.1 implied moderate to high disease activity, and DAS28-CRP less than (<)2.6 implied remission. | Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percent Change From Baseline in DAS28-CRP by Visit | DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP less than or equal to (=)3.2 implied low disease activity, DAS28-CRP greater than (>)3.2 to =5.1 implied moderate to high disease activity, and DAS28-CRP less than (<)2.6 implied remission. | Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit | 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: change from baseline >1.2 with DAS28 =3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to =5.1 or change from baseline >0.6 to =1.2 with DAS28 =5.1; non-responders: change from baseline =0.6, or change from baseline >0.6 and =1.2 with DAS28 >5.1. | Weeks 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit | 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: change from baseline >1.2 with DAS28 =3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to =5.1 or change from baseline >0.6 to =1.2 with DAS28 =5.1; non-responders: change from baseline =0.6, or change from baseline >0.6 and =1.2 with DAS28 >5.1. | Weeks 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percentage of Participants With No EULAR Response Based on DAS28 by Visit | 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: change from baseline >1.2 with DAS28 =3.2; moderate responders: change from baseline >1.2 with DAS28 >3.2 to =5.1 or change from baseline >0.6 to =1.2 with DAS28 =5.1; non-responders: change from baseline =0.6, or change from baseline >0.6 and =1.2 with DAS28 >5.1. | Weeks 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit | DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP =3.2 implied low disease activity. p-value of 9999 indicates p-value is not applicable. | Weeks 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percentage of Participants With DAS Remission (DAS <2.6) by Visit | DAS28-CRP was calculated from the swollen joint count and tender joint count using the 28 joints count and CRP (mg/L). Total score range: 0 to 9.4, higher score indicated more disease activity. DAS28-CRP <2.6 implied remission. p-value of 9999 indicates p-value is not applicable. | Weeks 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit | 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 3, 5, 9, 13, 17, 21 and 25 | |
Secondary | Percent Change From Baseline in HAQ-DI Score by Visit | 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 3, 5, 9, 13, 17, 21 and 25 |
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