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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)

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
PF-05280586
MabThera
Rituxan
Sponsored by
Pfizer
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring rheumatoid arthritis, rituximab, methotrexate, anti-TNF

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of Alabama at Bermingham
  • University of Alabama at Birmingham - Arthritis Clinical Intervention Program (ACIP) SRC 076
  • Rheumatology Associates of North Alabama, PC
  • ArthroCare, Arthritis Care & Research, PC
  • Mercy Clinic Hot Springs Communities
  • UCLA David Geffen School of Medicine
  • Ronald Reagan UCLA Medical Center
  • Desert Medical Advances
  • Advances In Medicine
  • New England Research Assoc. LLC
  • Arthritis Associates
  • University of South Florida - College of Medicine, Frank and Carol Morsani Center
  • Loyola Center for Health at Burr Ridge
  • Loyola Medical Medical Center Outpatient Center
  • Loyola University Medical Center Pharmacy
  • Illinois Bone and Joint Institute
  • Loyola Center for health at Oakbrook Terrace North
  • Bluegrass Community Research, Inc.
  • Klein & Associates, M.D., P.A.
  • Klein & Associates, M.D., P.A.
  • Clinical Pharmacology Study Group
  • UMass Memorial Medical Center - Memorial Campus
  • UMass Memorial Medical Center-Rheumatology Center-Memorial Campus
  • Bronson Internal Medicine & Rheumatology
  • Rheumatology/Arthritis Center
  • University Of Nevada School Of Medicine
  • Dartmouth Hitchcock Medical Center
  • North Shore-LIJ Health System - Division of Rheumatology and Allergy-Clinical Immunology
  • Box Arthritis & Rheumatology of the Carolinas, PLLC
  • Hickory Family Practice Associates
  • PMG Research of Hickory, LLC - PI's Main Office (Subject visit, IP Storage, Infusion, & Lab Draws)
  • PMG Research of Hickory
  • Cincinnati Rheumatic Disease Study Group, Inc.
  • Health Research of Oklahoma
  • Altoona Center for Clinical Research
  • The Arthritis Group
  • Clinical Research Center of Reading, LLP
  • Arthritis Associates, PLLC
  • Arthritis Clinic
  • West Tennessee Research Institute
  • Metroplex Clinical Research Center
  • Center For Clinical Trials Of Houston
  • Southwest Rheumatology Research LLC.
  • Rheumatology Research Unit
  • The Queen Elizabeth Hospital, Department of Rheumatology
  • St. Vincent's Hospital (Melbourne)
  • Centre de Rhumatologie de l'Est du Quebec
  • Clinique Medicale du Phare
  • Centre de Recherche Musculo-Squelettique
  • Pharmacie Matte et Petit
  • Centre de Rhumatologie St-Louis
  • Clinica Medellin S.A Sede Centro
  • Mix Supplier S.A
  • Rodrigo Botero S.A.S.
  • Cediul S.A.
  • Clinica Bonnadona - Prevenir S.A.
  • Clinica de la Costa Ltdz.
  • IPS Centro Integral de Reumatologia del Cairbe, CIRCARIBE S.A.S.
  • Sabbag Radiologos Ltda.
  • Cerid S.A.
  • Congregacion de las Hemanas Franciscanas Misioneras de Maria Auxiliadora - Clinica La Asuncion
  • IPS Clinica General del Norte S.A.
  • Centro de Reumatologia y Ortopedia
  • Schlosspark-Klinik GMBH, Internal Medicine II
  • The Chaim Sheba Medical Center Department of Internal Medicine B
  • Cliditer, S.A. de C.V.
  • Private Office
  • Centro De Investigacion Y Atencion Integral Durango CIAID
  • Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
  • LLC CDCR "Healthy Joints"
  • GBUZ City Clinical Hospital #7
  • State Institution of Healthcare "Regional Clinical Hospital for Wars' Veterans"
  • State Budgetary Institution of Healthcare of Nizhegorodskiy Region
  • St. Petersburg state Healthcare lnstitution 'Clinical Rheumatology Hospital No25
  • State Institute of Healthcare Samara Regional Clinical Hospital named after M.I.Kalinin
  • Llc Ava-Peter
  • Regional State Budget Institution of Healthcare "Tomsk Regional Clinical Hospital"
  • Panorama Medical Centre
  • Dr. Jan Fourie Medical Centre
  • Bexley Wing - St. James's University Hospital
  • Pharmacy Department, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust
  • "The University of Leeds,
  • Pharmacy Dispensing - Bexley Wing - St. James's University Hospital
  • Whipps Cross University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

A - PF-05280586

B - Rituximab EU

C- Rituximab-US

Arm Description

Outcomes

Primary Outcome Measures

Maximum Serum Concentration (Cmax) of Rituximab
Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered.
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.

Secondary Outcome Measures

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.
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.
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.
Minimum Post-Baseline CD19+ B-cell Count (/uL)
The lowest CD19+ B-cell count measured in a participant's blood post-baseline.
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.
Duration of B-cell Depletion (τB-cell) (Days)
The τB-cell is defined as the time interval over which the B-cell count was <0.3 cells/uL or the detection limit.
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.
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 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.
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L)
The percentage change from Baseline in circulating IgM by visit.
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.
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.
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.
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.
Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
February 1, 2012
Last Updated
October 30, 2019
Sponsor
Pfizer
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1. Study Identification

Unique Protocol Identification Number
NCT01526057
Brief Title
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)
Acronym
REFLECTIONS
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

2. Study Status

Record Verification Date
October 2019
Overall Recruitment Status
Completed
Study Start Date
March 20, 2012 (Actual)
Primary Completion Date
August 13, 2013 (Actual)
Study Completion Date
May 7, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Pfizer

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
rheumatoid arthritis, rituximab, methotrexate, anti-TNF

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
220 (Actual)

8. Arms, Groups, and Interventions

Arm Title
A - PF-05280586
Arm Type
Experimental
Arm Title
B - Rituximab EU
Arm Type
Active Comparator
Arm Title
C- Rituximab-US
Arm Type
Active Comparator
Intervention Type
Biological
Intervention Name(s)
PF-05280586
Intervention Description
1000 mg, IV on days 1 and 15
Intervention Type
Biological
Intervention Name(s)
MabThera
Intervention Description
1000 mg, IV on days 1 and 15
Intervention Type
Biological
Intervention Name(s)
Rituxan
Intervention Description
1000 mg, IV on days 1 and 15
Primary Outcome Measure Information:
Title
Maximum Serum Concentration (Cmax) of Rituximab
Description
Cmax is the peak serum concentration of study drug (rituximab) after a dose has been administered.
Time Frame
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
Title
AUC 0-inf of Rituximab
Description
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.
Time Frame
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 Outcome Measure Information:
Title
Rituximab AUC From Time 0 to 2 Weeks (AUC 0-2wk)
Description
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.
Time Frame
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
Title
Rituximab AUC From Time 0 to the Time of the Last Quantifiable Concentration (AUC 0-T)
Description
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.
Time Frame
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
Title
CD19+ B-cell Count AUC From Time 0 to the Last Measurement at Time T (AUC 0-T,B-cell)
Description
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.
Time Frame
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Title
Minimum Post-Baseline CD19+ B-cell Count (/uL)
Description
The lowest CD19+ B-cell count measured in a participant's blood post-baseline.
Time Frame
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Title
Time to Minimum Post-Baseline CD19+ B-cell Count (Weeks)
Description
The amount of time in weeks from baseline to the lowest observed CD19+ B-cell count.
Time Frame
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Title
Duration of B-cell Depletion (τB-cell) (Days)
Description
The τB-cell is defined as the time interval over which the B-cell count was <0.3 cells/uL or the detection limit.
Time Frame
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Title
Percentage of Participants With CD19+ B-cell Count Recovery
Description
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.
Time Frame
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25
Title
Area Under the CD19+ B-cell Count Concentration-time Profile (AUC 0-T, B-cell)
Description
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.
Time Frame
Baseline and Weeks 2, 3, 5, 9, 13, 17, 21 and 25 (EOT)
Title
Baseline and Change From Baseline in Circulating Immunoglobulin-M (IgM) by Visit (Grams Per Liter (g/L])
Description
The level of IgM in serum at Baseline and the change from Baseline at each subsequent visit.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25 (EOT)
Title
Percent (%) Change From Baseline in Circulating IgM by Visit (g/L)
Description
The percentage change from Baseline in circulating IgM by visit.
Time Frame
Baseline and Weeks 1, 2, 3, 4, 5, 9, 13, 17, 21 and 25
Title
Percentage of Participants With American College of Rheumatology (ACR) 20% Improvement (ACR20) Response by Visit
Description
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.
Time Frame
Weeks 3, 5, 9, 13, 17, 21 and 25
Title
Percentage of Participants With ACR 70% Improvement (ACR70) Response by Visit
Description
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.
Time Frame
Weeks 3, 5, 9, 13, 17, 21 and 25 (EOT)
Title
Percentage of Participants With ACR 50% Improvement (ACR50) Response by Visit
Description
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.
Time Frame
Weeks 3, 5, 9, 13, 17, 21 and 25
Title
Percentage of Participants by Anti-drug Antibody (ADA) Status
Description
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.
Time Frame
Days 1 up to Day 169.
Title
Percentage of Participants With Neutralizing Antibody (NAb) in Participants With a Positive ADA by Visit
Time Frame
Day 1 up to Day 169
Title
Change From Baseline in Disease Activity Score Based on 28-Joint Count and C-Reactive Protein (DAS28-CRP)
Description
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.
Time Frame
Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25
Title
Percent Change From Baseline in DAS28-CRP by Visit
Description
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.
Time Frame
Baseline and Weeks 3, 5, 9, 13, 17, 21 and 25
Title
Percentage of Participants With Good European League Against Rheumatism (EULAR) Response Based on Disease Activity Score Based on 28-Joint Count (DAS28) by Visit
Description
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.
Time Frame
Weeks 3, 5, 9, 13, 17, 21 and 25
Title
Percentage of Participants With Moderate EULAR Response Based on Disease Activity Score Based on DAS28 by Visit
Description
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.
Time Frame
Weeks 3, 5, 9, 13, 17, 21 and 25
Title
Percentage of Participants With No EULAR Response Based on DAS28 by Visit
Description
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.
Time Frame
Weeks 3, 5, 9, 13, 17, 21 and 25
Title
Percentage of Participants With Low Disease Activity Score (DAS <=3.2) by Visit
Description
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.
Time Frame
Weeks 3, 5, 9, 13, 17, 21 and 25
Title
Percentage of Participants With DAS Remission (DAS <2.6) by Visit
Description
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.
Time Frame
Weeks 3, 5, 9, 13, 17, 21 and 25
Title
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) by Visit
Description
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.
Time Frame
Baseline, Week 3, 5, 9, 13, 17, 21 and 25
Title
Percent Change From Baseline in HAQ-DI Score by Visit
Description
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.
Time Frame
Baseline, Week 3, 5, 9, 13, 17, 21 and 25

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pfizer CT.gov Call Center
Organizational Affiliation
Pfizer
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Bermingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35249
Country
United States
Facility Name
University of Alabama at Birmingham - Arthritis Clinical Intervention Program (ACIP) SRC 076
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
Rheumatology Associates of North Alabama, PC
City
Huntsville
State/Province
Alabama
ZIP/Postal Code
35801
Country
United States
Facility Name
ArthroCare, Arthritis Care & Research, PC
City
Gilbert
State/Province
Arizona
ZIP/Postal Code
85234
Country
United States
Facility Name
Mercy Clinic Hot Springs Communities
City
Hot Springs
State/Province
Arkansas
ZIP/Postal Code
71913
Country
United States
Facility Name
UCLA David Geffen School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095-1670
Country
United States
Facility Name
Ronald Reagan UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
Desert Medical Advances
City
Palm Desert
State/Province
California
ZIP/Postal Code
92260
Country
United States
Facility Name
Advances In Medicine
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
Facility Name
New England Research Assoc. LLC
City
Trumbull
State/Province
Connecticut
ZIP/Postal Code
06611
Country
United States
Facility Name
Arthritis Associates
City
Orlando
State/Province
Florida
ZIP/Postal Code
32804
Country
United States
Facility Name
University of South Florida - College of Medicine, Frank and Carol Morsani Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Facility Name
Loyola Center for Health at Burr Ridge
City
Burr Ridge
State/Province
Illinois
ZIP/Postal Code
60527
Country
United States
Facility Name
Loyola Medical Medical Center Outpatient Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Loyola University Medical Center Pharmacy
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Illinois Bone and Joint Institute
City
Morton Grove
State/Province
Illinois
ZIP/Postal Code
60053
Country
United States
Facility Name
Loyola Center for health at Oakbrook Terrace North
City
Oakbrook Terrace
State/Province
Illinois
ZIP/Postal Code
60181
Country
United States
Facility Name
Bluegrass Community Research, Inc.
City
Lexington
State/Province
Kentucky
ZIP/Postal Code
40504
Country
United States
Facility Name
Klein & Associates, M.D., P.A.
City
Cumberland
State/Province
Maryland
ZIP/Postal Code
21502
Country
United States
Facility Name
Klein & Associates, M.D., P.A.
City
Hagerstown
State/Province
Maryland
ZIP/Postal Code
21740
Country
United States
Facility Name
Clinical Pharmacology Study Group
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
UMass Memorial Medical Center - Memorial Campus
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
UMass Memorial Medical Center-Rheumatology Center-Memorial Campus
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01605
Country
United States
Facility Name
Bronson Internal Medicine & Rheumatology
City
Battle Creek
State/Province
Michigan
ZIP/Postal Code
49015
Country
United States
Facility Name
Rheumatology/Arthritis Center
City
Lansing
State/Province
Michigan
ZIP/Postal Code
48910
Country
United States
Facility Name
University Of Nevada School Of Medicine
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89102
Country
United States
Facility Name
Dartmouth Hitchcock Medical Center
City
Lebanon
State/Province
New Hampshire
ZIP/Postal Code
03756
Country
United States
Facility Name
North Shore-LIJ Health System - Division of Rheumatology and Allergy-Clinical Immunology
City
Great Neck
State/Province
New York
ZIP/Postal Code
11021
Country
United States
Facility Name
Box Arthritis & Rheumatology of the Carolinas, PLLC
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28210
Country
United States
Facility Name
Hickory Family Practice Associates
City
Hickory
State/Province
North Carolina
ZIP/Postal Code
28601
Country
United States
Facility Name
PMG Research of Hickory, LLC - PI's Main Office (Subject visit, IP Storage, Infusion, & Lab Draws)
City
Hickory
State/Province
North Carolina
ZIP/Postal Code
28602
Country
United States
Facility Name
PMG Research of Hickory
City
Hickory
State/Province
North Carolina
ZIP/Postal Code
28602
Country
United States
Facility Name
Cincinnati Rheumatic Disease Study Group, Inc.
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Health Research of Oklahoma
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73103
Country
United States
Facility Name
Altoona Center for Clinical Research
City
Duncansville
State/Province
Pennsylvania
ZIP/Postal Code
16635
Country
United States
Facility Name
The Arthritis Group
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19152
Country
United States
Facility Name
Clinical Research Center of Reading, LLP
City
Wyomissing
State/Province
Pennsylvania
ZIP/Postal Code
19610
Country
United States
Facility Name
Arthritis Associates, PLLC
City
Hixson
State/Province
Tennessee
ZIP/Postal Code
37343
Country
United States
Facility Name
Arthritis Clinic
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38305
Country
United States
Facility Name
West Tennessee Research Institute
City
Jackson
State/Province
Tennessee
ZIP/Postal Code
38305
Country
United States
Facility Name
Metroplex Clinical Research Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75231
Country
United States
Facility Name
Center For Clinical Trials Of Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77004
Country
United States
Facility Name
Southwest Rheumatology Research LLC.
City
Mesquite
State/Province
Texas
ZIP/Postal Code
75150
Country
United States
Facility Name
Rheumatology Research Unit
City
Maroochydore
State/Province
Queensland
ZIP/Postal Code
4558
Country
Australia
Facility Name
The Queen Elizabeth Hospital, Department of Rheumatology
City
Woodville South
State/Province
South Australia
ZIP/Postal Code
5011
Country
Australia
Facility Name
St. Vincent's Hospital (Melbourne)
City
Fitzroy
State/Province
Victoria
ZIP/Postal Code
03065
Country
Australia
Facility Name
Centre de Rhumatologie de l'Est du Quebec
City
Rimouski
State/Province
Quebec
ZIP/Postal Code
G5L 8W1
Country
Canada
Facility Name
Clinique Medicale du Phare
City
Rimouski
State/Province
Quebec
ZIP/Postal Code
G5L IJ5
Country
Canada
Facility Name
Centre de Recherche Musculo-Squelettique
City
Trois-Rivieres
State/Province
Quebec
ZIP/Postal Code
G8Z 1Y2
Country
Canada
Facility Name
Pharmacie Matte et Petit
City
Quebec
ZIP/Postal Code
G1V 3M7
Country
Canada
Facility Name
Centre de Rhumatologie St-Louis
City
Quebec
ZIP/Postal Code
G1W 4R4
Country
Canada
Facility Name
Clinica Medellin S.A Sede Centro
City
Medellin
State/Province
Antioquia
Country
Colombia
Facility Name
Mix Supplier S.A
City
Medellin
State/Province
Antioquia
Country
Colombia
Facility Name
Rodrigo Botero S.A.S.
City
Medellin
State/Province
Antioquia
Country
Colombia
Facility Name
Cediul S.A.
City
Barranquilla
State/Province
Atlantico
Country
Colombia
Facility Name
Clinica Bonnadona - Prevenir S.A.
City
Barranquilla
State/Province
Atlantico
Country
Colombia
Facility Name
Clinica de la Costa Ltdz.
City
Barranquilla
State/Province
Atlantico
Country
Colombia
Facility Name
IPS Centro Integral de Reumatologia del Cairbe, CIRCARIBE S.A.S.
City
Barranquilla
State/Province
Atlantico
Country
Colombia
Facility Name
Sabbag Radiologos Ltda.
City
Barranquilla
State/Province
Atlantico
Country
Colombia
Facility Name
Cerid S.A.
City
Barranquilla, Colombia
State/Province
Atlántico
Country
Colombia
Facility Name
Congregacion de las Hemanas Franciscanas Misioneras de Maria Auxiliadora - Clinica La Asuncion
City
Barranquilla, Colombia
State/Province
Atlántico
Country
Colombia
Facility Name
IPS Clinica General del Norte S.A.
City
Barranquilla, Colombia
State/Province
Atlántico
Country
Colombia
Facility Name
Centro de Reumatologia y Ortopedia
City
Barranquilla
State/Province
Atlántico
Country
Colombia
Facility Name
Schlosspark-Klinik GMBH, Internal Medicine II
City
Berlin
ZIP/Postal Code
14059
Country
Germany
Facility Name
The Chaim Sheba Medical Center Department of Internal Medicine B
City
Ramat Gan
ZIP/Postal Code
52621
Country
Israel
Facility Name
Cliditer, S.A. de C.V.
City
Mexico
State/Province
D.f.
ZIP/Postal Code
06700
Country
Mexico
Facility Name
Private Office
City
Guadalajara
State/Province
Jalisco
ZIP/Postal Code
06726
Country
Mexico
Facility Name
Centro De Investigacion Y Atencion Integral Durango CIAID
City
Durango
ZIP/Postal Code
34270
Country
Mexico
Facility Name
Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.
City
San Luis Potosi
ZIP/Postal Code
78200
Country
Mexico
Facility Name
LLC CDCR "Healthy Joints"
City
Novosibirsk
State/Province
Novosibirsk Region
ZIP/Postal Code
630091
Country
Russian Federation
Facility Name
GBUZ City Clinical Hospital #7
City
Kazan
State/Province
Tatarstan
ZIP/Postal Code
420103
Country
Russian Federation
Facility Name
State Institution of Healthcare "Regional Clinical Hospital for Wars' Veterans"
City
Kemerovo
ZIP/Postal Code
650000
Country
Russian Federation
Facility Name
State Budgetary Institution of Healthcare of Nizhegorodskiy Region
City
Nizhny Novgorod
ZIP/Postal Code
603005
Country
Russian Federation
Facility Name
St. Petersburg state Healthcare lnstitution 'Clinical Rheumatology Hospital No25
City
Saint-Petersburg
ZIP/Postal Code
190068
Country
Russian Federation
Facility Name
State Institute of Healthcare Samara Regional Clinical Hospital named after M.I.Kalinin
City
Samara
ZIP/Postal Code
443095
Country
Russian Federation
Facility Name
Llc Ava-Peter
City
St. Petersburg
ZIP/Postal Code
191014
Country
Russian Federation
Facility Name
Regional State Budget Institution of Healthcare "Tomsk Regional Clinical Hospital"
City
Tomsk
ZIP/Postal Code
634063
Country
Russian Federation
Facility Name
Panorama Medical Centre
City
Panorama
State/Province
Cape Town
ZIP/Postal Code
7500
Country
South Africa
Facility Name
Dr. Jan Fourie Medical Centre
City
Dundee
State/Province
Kwa-zulu Natal
ZIP/Postal Code
3000
Country
South Africa
Facility Name
Bexley Wing - St. James's University Hospital
City
Leeds
State/Province
UK
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Pharmacy Department, Leeds General Infirmary, Leeds Teaching Hospitals NHS Trust
City
Leeds
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
"The University of Leeds,
City
Leeds
ZIP/Postal Code
LS7 4SA
Country
United Kingdom
Facility Name
Pharmacy Dispensing - Bexley Wing - St. James's University Hospital
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Whipps Cross University Hospital
City
London
ZIP/Postal Code
E11 1NR
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
IPD Sharing URL
https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests
Citations:
PubMed Identifier
27530379
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.
Results Reference
derived
Links:
URL
https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=B3281001&StudyName=A%20Pharmacokinetic/Pharmacodynamic%20Study%20Comparing%20PF-05280586%20To%20Rituximab%20In%20Subjects%20With%20Active%20Rheumatoid%20Arthritis%20With%20An%20Inadequate%20Res
Description
To obtain contact information for a study center near you, click here.

Learn more about this trial

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)

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