Clinical trial NCT01526057: 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)
Official 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Rheumatoid Arthritis
Keywords: rheumatoid arthritis
rituximab
methotrexate
anti-TNF
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2012-02-03
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum Serum Concentration (Cmax) of Rituximab
timeFrame: 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
measure: AUC 0-inf of Rituximab
timeFrame: 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:
measure: Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)
timeFrame: 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
measure: Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T)
timeFrame: 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
measure: CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell)
timeFrame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
measure: Minimum Post-Baseline CD19+ B-cell Count (/uL)
timeFrame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
measure: Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)
timeFrame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
measure: Duration of B-cell Depletion (τB-cell) (Days)
timeFrame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
measure: Percentage of Participants With CD19+ B-cell Count Recovery
timeFrame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25
measure: Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell)
timeFrame: Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
measure: Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L])
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 (EOT)
measure: Percent (%) Change From Baseline in Circulating IgM by Visit (g/L)
timeFrame: Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25
measure: Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit
timeFrame: Weeks 3, 5, 9, 13, 17, 21 and 25
measure: Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit
timeFrame: Weeks 3, 5, 9, 13, 17, 21 and 25 (EOT)
measure: Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit
timeFrame: Weeks 3, 5, 9, 13, 17, 21 and 25
measure: Percentage of Participants by Anti-drug Antibody (ADA) Status
timeFrame: Days 1 up to Day 169.
measure: Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit
timeFrame: Day 1 up to Day 169
measure: Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP)
timeFrame: Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25
measure: Percent Change From Baseline in DAS28-CRP by Visit
timeFrame: Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25
measure: Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit
timeFrame: Weeks 3, 5, 9, 13, 17, 21 and 25
measure: Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit
timeFrame: Weeks 3, 5, 9, 13, 17, 21 and 25
measure: Percentage of Participants With No EULAR Response Based on DAS28 by Visit
timeFrame: Weeks 3, 5, 9, 13, 17, 21 and 25
measure: Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit
timeFrame: Weeks 3, 5, 9, 13, 17, 21 and 25
measure: Percentage of Participants With DAS Remission (DAS <2.6) by Visit
timeFrame: Weeks 3, 5, 9, 13, 17, 21 and 25
measure: Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit
timeFrame: Baseline, Week 3, 5, 9, 13, 17, 21 and 25
measure: Percent Change From Baseline in HAQ-DI Score by Visit
timeFrame: Baseline, Week 3, 5, 9, 13, 17, 21 and 25
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Bermingham
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham - Arthritis Clinical Intervention Program (ACIP) SRC 076
state: Alabama
city: Huntsville
country: United States
facility: Rheumatology Associates of North Alabama, PC
state: Alabama
city: Gilbert
country: United States
facility: ArthroCare, Arthritis Care & Research, PC
state: Arizona
city: Hot Springs
country: United States
facility: Mercy Clinic Hot Springs Communities
state: Arkansas
city: Los Angeles
country: United States
facility: UCLA David Geffen School of Medicine
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Palm Desert
country: United States
facility: Desert Medical Advances
state: California
city: Rancho Mirage
country: United States
facility: Advances In Medicine
state: California
city: Trumbull
country: United States
facility: New England Research Assoc. LLC
state: Connecticut
city: Orlando
country: United States
facility: Arthritis Associates
state: Florida
city: Tampa
country: United States
facility: University of South Florida - College of Medicine, Frank and Carol Morsani Center
state: Florida
city: Burr Ridge
country: United States
facility: Loyola Center for Health at Burr Ridge
state: Illinois
city: Maywood
country: United States
facility: Loyola Medical Medical Center Outpatient Center
state: Illinois
city: Maywood
country: United States
facility: Loyola University Medical Center Pharmacy
state: Illinois
city: Morton Grove
country: United States
facility: Illinois Bone and Joint Institute
state: Illinois
city: Oakbrook Terrace
country: United States
facility: Loyola Center for health at Oakbrook Terrace North
state: Illinois
city: Lexington
country: United States
facility: Bluegrass Community Research, Inc.
state: Kentucky
city: Cumberland
country: United States
facility: Klein & Associates, M.D., P.A.
state: Maryland
city: Hagerstown
country: United States
facility: Klein & Associates, M.D., P.A.
state: Maryland
city: Worcester
country: United States
facility: Clinical Pharmacology Study Group
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center - Memorial Campus
state: Massachusetts
city: Worcester
country: United States
facility: UMass Memorial Medical Center-Rheumatology Center-Memorial Campus
state: Massachusetts
city: Battle Creek
country: United States
facility: Bronson Internal Medicine & Rheumatology
state: Michigan
city: Lansing
country: United States
facility: Rheumatology/Arthritis Center
state: Michigan
city: Las Vegas
country: United States
facility: University Of Nevada School Of Medicine
state: Nevada
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Great Neck
country: United States
facility: North Shore-LIJ Health System - Division of Rheumatology and Allergy-Clinical Immunology
state: New York
city: Charlotte
country: United States
facility: Box Arthritis & Rheumatology of the Carolinas, PLLC
state: North Carolina
city: Hickory
country: United States
facility: Hickory Family Practice Associates
state: North Carolina
city: Hickory
country: United States
facility: PMG Research of Hickory, LLC - PI's Main Office (Subject visit, IP Storage, Infusion, & Lab Draws)
state: North Carolina
city: Hickory
country: United States
facility: PMG Research of Hickory
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Rheumatic Disease Study Group, Inc.
state: Ohio
city: Oklahoma City
country: United States
facility: Health Research of Oklahoma
state: Oklahoma
city: Duncansville
country: United States
facility: Altoona Center for Clinical Research
state: Pennsylvania
city: Philadelphia
country: United States
facility: The Arthritis Group
state: Pennsylvania
city: Wyomissing
country: United States
facility: Clinical Research Center of Reading, LLP
state: Pennsylvania
city: Hixson
country: United States
facility: Arthritis Associates, PLLC
state: Tennessee
city: Jackson
country: United States
facility: Arthritis Clinic
state: Tennessee
city: Jackson
country: United States
facility: West Tennessee Research Institute
state: Tennessee
city: Dallas
country: United States
facility: Metroplex Clinical Research Center
state: Texas
city: Houston
country: United States
facility: Center For Clinical Trials Of Houston
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research LLC.
state: Texas
city: Maroochydore
country: Australia
facility: Rheumatology Research Unit
state: Queensland
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital, Department of Rheumatology
state: South Australia
city: Fitzroy
country: Australia
facility: St. Vincent's Hospital (Melbourne)
state: Victoria
city: Rimouski
country: Canada
facility: Centre de Rhumatologie de l'Est du Quebec
state: Quebec
city: Rimouski
country: Canada
facility: Clinique Medicale du Phare
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Centre de Recherche Musculo-Squelettique
state: Quebec
city: Quebec
country: Canada
facility: Pharmacie Matte et Petit
city: Quebec
country: Canada
facility: Centre de Rhumatologie St-Louis
city: Medellin
country: Colombia
facility: Clinica Medellin S.A Sede Centro
state: Antioquia
city: Medellin
country: Colombia
facility: Mix Supplier S.A
state: Antioquia
city: Medellin
country: Colombia
facility: Rodrigo Botero S.A.S.
state: Antioquia
city: Barranquilla
country: Colombia
facility: Cediul S.A.
state: Atlantico
city: Barranquilla
country: Colombia
facility: Clinica Bonnadona - Prevenir S.A.
state: Atlantico
city: Barranquilla
country: Colombia
facility: Clinica de la Costa Ltdz.
state: Atlantico
city: Barranquilla
country: Colombia
facility: IPS Centro Integral de Reumatologia del Cairbe, CIRCARIBE S.A.S.
state: Atlantico
city: Barranquilla
country: Colombia
facility: Sabbag Radiologos Ltda.
state: Atlantico
city: Barranquilla, Colombia
country: Colombia
facility: Cerid S.A.
state: Atlántico
city: Barranquilla, Colombia
country: Colombia
facility: Congregacion de las Hemanas Franciscanas Misioneras de Maria Auxiliadora - Clinica La Asuncion
state: Atlántico
city: Barranquilla, Colombia
country: Colombia
facility: IPS Clinica General del Norte S.A.
state: Atlántico
city: Barranquilla
country: Colombia
facility: Centro de Reumatologia y Ortopedia
state: Atlántico
city: Berlin
country: Germany
facility: Schlosspark-Klinik GMBH, Internal Medicine II
city: Ramat Gan
country: Israel
facility: The Chaim Sheba Medical Center Department of Internal Medicine B
city: Mexico
country: Mexico
facility: Cliditer, S.A. de C.V.
state: D.f.
city: Guadalajara
country: Mexico
facility: Private Office
state: Jalisco
city: Durango
country: Mexico
facility: Centro De Investigacion Y Atencion Integral Durango CIAID
city: San Luis Potosi
country: Mexico
facility: Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
city: Novosibirsk
country: Russian Federation
facility: LLC CDCR "Healthy Joints"
state: Novosibirsk Region
city: Kazan
country: Russian Federation
facility: GBUZ City Clinical Hospital #7
state: Tatarstan
city: Kemerovo
country: Russian Federation
facility: State Institution of Healthcare "Regional Clinical Hospital for Wars' Veterans"
city: Nizhny Novgorod
country: Russian Federation
facility: State Budgetary Institution of Healthcare of Nizhegorodskiy Region
city: Saint-Petersburg
country: Russian Federation
facility: St. Petersburg state Healthcare lnstitution 'Clinical Rheumatology Hospital No25
city: Samara
country: Russian Federation
facility: State Institute of Healthcare Samara Regional Clinical Hospital named after M.I.Kalinin
city: St. Petersburg
country: Russian Federation
facility: Llc Ava-Peter
city: Tomsk
country: Russian Federation
facility: Regional State Budget Institution of Healthcare "Tomsk Regional Clinical Hospital"
city: Panorama
country: South Africa
facility: Panorama Medical Centre
state: Cape Town
city: Dundee
country: South Africa
facility: Dr. Jan Fourie Medical Centre
state: Kwa-zulu Natal
city: Leeds
country: United Kingdom
facility: Bexley Wing - St. James's University Hospital
state: UK
city: Leeds
country: United Kingdom
facility: Pharmacy Department, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust
city: Leeds
country: United Kingdom
facility: "The University of Leeds,
city: Leeds
country: United Kingdom
facility: Pharmacy Dispensing - Bexley Wing - St. James's University Hospital
city: London
country: United Kingdom
facility: Whipps Cross University Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.