A Pharmacokinetic/Pharmacodynamic Study Comparing PF-05280586 To Rituximab In Subjects With Active Rheumatoid Arthritis With An Inadequate Response To TNF Inhibitors (REFLECTIONS B328-01)
REFLECTIONS
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
3 other identifiers
interventional
220
10 countries
84
Brief Summary
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2 rheumatoid-arthritis
Started Mar 2012
Typical duration for phase_2 rheumatoid-arthritis
84 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
February 1, 2012
CompletedFirst Posted
Study publicly available on registry
February 3, 2012
CompletedStudy Start
First participant enrolled
March 20, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 13, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
May 7, 2014
CompletedResults Posted
Study results publicly available
November 19, 2019
CompletedNovember 19, 2019
October 1, 2019
1.4 years
February 1, 2012
September 6, 2019
October 30, 2019
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
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 Outcomes (24)
Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)
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
Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-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
CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell)
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Minimum Post-Baseline CD19+ B-cell Count (/uL)
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
- +19 more secondary outcomes
Study Arms (3)
A - PF-05280586
EXPERIMENTALB - Rituximab EU
ACTIVE COMPARATORC- Rituximab-US
ACTIVE COMPARATORInterventions
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Pfizerlead
Study Sites (84)
University of Alabama at Bermingham
Birmingham, Alabama, 35249, United States
University of Alabama at Birmingham - Arthritis Clinical Intervention Program (ACIP) SRC 076
Birmingham, Alabama, 35294, United States
Rheumatology Associates of North Alabama, PC
Huntsville, Alabama, 35801, United States
ArthroCare, Arthritis Care & Research, PC
Gilbert, Arizona, 85234, United States
Mercy Clinic Hot Springs Communities
Hot Springs, Arkansas, 71913, United States
UCLA David Geffen School of Medicine
Los Angeles, California, 90095-1670, United States
Ronald Reagan UCLA Medical Center
Los Angeles, California, 90095, United States
Desert Medical Advances
Palm Desert, California, 92260, United States
Advances In Medicine
Rancho Mirage, California, 92270, United States
New England Research Assoc. LLC
Trumbull, Connecticut, 06611, United States
Arthritis Associates
Orlando, Florida, 32804, United States
University of South Florida - College of Medicine, Frank and Carol Morsani Center
Tampa, Florida, 33612, United States
Loyola Center for Health at Burr Ridge
Burr Ridge, Illinois, 60527, United States
Loyola Medical Medical Center Outpatient Center
Maywood, Illinois, 60153, United States
Loyola University Medical Center Pharmacy
Maywood, Illinois, 60153, United States
Illinois Bone and Joint Institute
Morton Grove, Illinois, 60053, United States
Loyola Center for health at Oakbrook Terrace North
Oakbrook Terrace, Illinois, 60181, United States
Bluegrass Community Research, Inc.
Lexington, Kentucky, 40504, United States
Klein & Associates, M.D., P.A.
Cumberland, Maryland, 21502, United States
Klein & Associates, M.D., P.A.
Hagerstown, Maryland, 21740, United States
Clinical Pharmacology Study Group
Worcester, Massachusetts, 01605, United States
UMass Memorial Medical Center - Memorial Campus
Worcester, Massachusetts, 01605, United States
UMass Memorial Medical Center-Rheumatology Center-Memorial Campus
Worcester, Massachusetts, 01605, United States
Bronson Internal Medicine & Rheumatology
Battle Creek, Michigan, 49015, United States
Rheumatology/Arthritis Center
Lansing, Michigan, 48910, United States
University Of Nevada School Of Medicine
Las Vegas, Nevada, 89102, United States
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, 03756, United States
North Shore-LIJ Health System - Division of Rheumatology and Allergy-Clinical Immunology
Great Neck, New York, 11021, United States
Box Arthritis & Rheumatology of the Carolinas, PLLC
Charlotte, North Carolina, 28210, United States
Hickory Family Practice Associates
Hickory, North Carolina, 28601, United States
PMG Research of Hickory, LLC - PI's Main Office (Subject visit, IP Storage, Infusion, & Lab Draws)
Hickory, North Carolina, 28602, United States
PMG Research of Hickory
Hickory, North Carolina, 28602, United States
Cincinnati Rheumatic Disease Study Group, Inc.
Cincinnati, Ohio, 45219, United States
Health Research of Oklahoma
Oklahoma City, Oklahoma, 73103, United States
Altoona Center for Clinical Research
Duncansville, Pennsylvania, 16635, United States
The Arthritis Group
Philadelphia, Pennsylvania, 19152, United States
Clinical Research Center of Reading, LLP
Wyomissing, Pennsylvania, 19610, United States
Arthritis Associates, PLLC
Hixson, Tennessee, 37343, United States
Arthritis Clinic
Jackson, Tennessee, 38305, United States
West Tennessee Research Institute
Jackson, Tennessee, 38305, United States
Metroplex Clinical Research Center
Dallas, Texas, 75231, United States
Center For Clinical Trials Of Houston
Houston, Texas, 77004, United States
Southwest Rheumatology Research LLC.
Mesquite, Texas, 75150, United States
Rheumatology Research Unit
Maroochydore, Queensland, 4558, Australia
The Queen Elizabeth Hospital, Department of Rheumatology
Woodville South, South Australia, 5011, Australia
St. Vincent's Hospital (Melbourne)
Fitzroy, Victoria, 03065, Australia
Pharmacie Matte et Petit
Québec, Quebec, G1V 3M7, Canada
Centre de Rhumatologie St-Louis
Québec, Quebec, G1W 4R4, Canada
Centre de Rhumatologie de l'Est du Quebec
Rimouski, Quebec, G5L 8W1, Canada
Clinique Medicale du Phare
Rimouski, Quebec, G5L IJ5, Canada
Centre de Recherche Musculo-Squelettique
Trois-Rivières, Quebec, G8Z 1Y2, Canada
Clinica Medellin S.A Sede Centro
Medellín, Antioquia, Colombia
Mix Supplier S.A
Medellín, Antioquia, Colombia
Rodrigo Botero S.A.S.
Medellín, Antioquia, Colombia
Cediul S.A.
Barranquilla, Atlántico, Colombia
Centro de Reumatologia y Ortopedia
Barranquilla, Atlántico, Colombia
Clinica Bonnadona - Prevenir S.A.
Barranquilla, Atlántico, Colombia
Clinica de la Costa Ltdz.
Barranquilla, Atlántico, Colombia
IPS Centro Integral de Reumatologia del Cairbe, CIRCARIBE S.A.S.
Barranquilla, Atlántico, Colombia
Sabbag Radiologos Ltda.
Barranquilla, Atlántico, 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
Schlosspark-Klinik GMBH, Internal Medicine II
Berlin, 14059, Germany
The Chaim Sheba Medical Center Department of Internal Medicine B
Ramat Gan, 52621, Israel
Cliditer, S.A. de C.V.
México, D.F., 06700, Mexico
Private Office
Guadalajara, Jalisco, 06726, Mexico
Centro De Investigacion Y Atencion Integral Durango CIAID
Durango, 34270, Mexico
Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
San Luis Potosí City, 78200, Mexico
LLC CDCR "Healthy Joints"
Novosibirsk, Novosibirsk Oblast, 630091, Russia
GBUZ City Clinical Hospital #7
Kazan', Tatarstan Republic, 420103, Russia
State Institution of Healthcare "Regional Clinical Hospital for Wars' Veterans"
Kemerovo, 650000, Russia
State Budgetary Institution of Healthcare of Nizhegorodskiy Region
Nizhny Novgorod, 603005, Russia
St. Petersburg state Healthcare lnstitution 'Clinical Rheumatology Hospital No25
Saint Petersburg, 190068, Russia
Llc Ava-Peter
Saint Petersburg, 191014, Russia
State Institute of Healthcare Samara Regional Clinical Hospital named after M.I.Kalinin
Samara, 443095, Russia
Regional State Budget Institution of Healthcare "Tomsk Regional Clinical Hospital"
Tomsk, 634063, Russia
Panorama Medical Centre
Panorama, CAPE TOWN, 7500, South Africa
Dr. Jan Fourie Medical Centre
Dundee, KwaZulu-Natal, 3000, South Africa
Bexley Wing - St. James's University Hospital
Leeds, UK, LS9 7TF, United Kingdom
Pharmacy Department, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust
Leeds, LS1 3EX, United Kingdom
"The University of Leeds,
Leeds, LS7 4SA, United Kingdom
Pharmacy Dispensing - Bexley Wing - St. James's University Hospital
Leeds, LS9 7TF, United Kingdom
Whipps Cross University Hospital
London, E11 1NR, United Kingdom
Related Publications (1)
Williams JH, Hutmacher MM, Zierhut ML, Becker JC, Gumbiner B, Spencer-Green G, Melia LA, Liao KH, Suster M, Yin D, Li R, Meng X. Comparative assessment of clinical response in patients with rheumatoid arthritis between PF-05280586, a proposed rituximab biosimilar, and rituximab. Br J Clin Pharmacol. 2016 Dec;82(6):1568-1579. doi: 10.1111/bcp.13094. Epub 2016 Sep 22.
PMID: 27530379DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- LTE60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
February 1, 2012
First Posted
February 3, 2012
Study Start
March 20, 2012
Primary Completion
August 13, 2013
Study Completion
May 7, 2014
Last Updated
November 19, 2019
Results First Posted
November 19, 2019
Record last verified: 2019-10
Data Sharing
- IPD Sharing
- Will share
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.