Subcutaneous Treatment In Randomized Subjects To Evaluate Safety And Efficacy In Generalized Lupus Erythematosus (BUTTERFLY)

A Double-blind, Randomized, Placebo-controlled, Multicenter Dose-ranging Study To Evaluate The Efficacy And Safety Of Pf-04236921 In Subjects With Systemic Lupus Erythematosus (Sle)

The objective of this study is to evaluate and compare efficacy of 3 dose levels of PF-04236921 to placebo in subjects with generalized lupus using a measure called the Systemic Lupus Erythematosus (SLE) Responder Index. The study will evaluate secondary and exploratory measures as well.

Study Overview

• Status: Completed
• Conditions: Lupus Erythematosus, Systemic
• Intervention / Treatment: Biological: PF-04236921; Biological: PF-04236921

• Study Type: Interventional
• Enrollment (Actual): 183
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • C.a.b.a, Argentina, C1431FWO
    • Centro de Educacion Medica e Investigaciones Clinicas "Norberto Quirno" Cemic
  • San Juan, Argentina, J5402DIL
    • Centro Polivalente de Asistencia e Investigación Clínica - CER- San Juan
  • Buenos Aires
    • La Plata, Buenos Aires, Argentina, B1902COS
      • Framingham Centro Medico
  • Santa FE
    • Rosario, Santa FE, Argentina, S2000PBJ
      • Instituto CAICI S.R.L.
  • Tucuman
    • San Miguel de Tucuman, Tucuman, Argentina, T4000AXL
      • Centro Medico Privado de Reumatologia
• Chile
  • RM
    • Santiago, RM, Chile, 7501126
      • Centro de Estudios Reumatologicos
    • Santiago, RM, Chile
      • Centro Medico Prosalud
  • Region Metropolitana
    • Santiago, Region Metropolitana, Chile, 7510186
      • Sociedad Medica del Aparato Locomotor S.A. (SOMEAL)
• Colombia
  • Bogota, Colombia
    • Farmamix Ltda.
  • Antioquia
    • Envigado, Antioquia, Colombia
      • Centro Integral de Reumatologia REUMALAB S.A.S.
    • Medellin, Antioquia, Colombia
      • Hospital Pablo Tobon Uribe
  • Antioquia, Colombia
    • Envigado, Antioquia, Colombia, Colombia
      • Mix Supplier S.A.
  • Atlantico
    • Barranquilla, Atlantico, Colombia
      • Organizacion Clinica General del Norte S.A.
    • Barranquilla, Atlantico, Colombia
      • Centro Integral de Reumatología del Caribe Circaribe SAS
    • Barranquilla, Atlantico, Colombia
      • Congregacion de Hermanas Franciscanas Misioneras de Maria Auxiliadora- Clinica Asunción
  • Cundimarca
    • Bogota, Distrito Capital, Cundimarca, Colombia
      • Farmamix Ltda.
  • Cundinamarca
    • Bogota, Cundinamarca, Colombia
      • Riesgo De Fractura S.A
    • Bogota, Cundinamarca, Colombia
      • Centro Integral de Reumatologia e Inmunologia S.A.S.- CIREI S.A.S.
  • Santander
    • Bucaramanga, Santander, Colombia
      • Servimed E.U
• Germany
  • Berlin, Germany, 10117
    • Charite - Universitaetsmedizin Berlin
  • Berlin, Germany, 14059
    • Charité University Medicine Berlin. Schlosspark-Klinik
  • Erlangen, Germany, 91054
    • Universitaetsklinikum Erlangen
  • Frankfurt/Main, Germany, 60528
    • CIRI am Klinikum der Goethe-Universitaet
  • Koeln, Germany, 50937
    • Universitaetsklinikum Koeln
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig AoeR, Department fuer Innere Medizin
• Hungary
  • Budapest, Hungary, 1036
    • Qualiclinic Kft.
  • Debrecen, Hungary, H-4032
    • Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum
  • Gyula, Hungary, 5700
    • Bekes Megyei Kepviselo-testulet Pandy Kalman Korhaz Infektologia, Hepatologia es Immunologia
• Korea, Republic of
  • Busan, Korea, Republic of, 602-715
    • Dong-A University Medical Center 1
• Moldova, Republic of
  • Md-2025
    • Chisinau, Md-2025, Moldova, Republic of, 2025
      • Spitalul Clinic Republican
• Peru
  • Arequipa, Peru, AQ 54
    • Unidad de Investigación en Medicina Interna y Enfermedades Críticas
  • Lima
    • San Isidro, Lima, Peru, Lima 27
      • Centro de Investigacion REUMED, Clinica Anglo Americana
    • Santiago de Surco, Lima, Peru, Lima 33
      • Investigaciones Clinicas SAC
    • Surco, Lima, Peru, Lima 33
      • Investigaciones Clinicas SAC
• Poland
  • Elblag, Poland, 82-300
    • NZOZ Centrum Reumatologiczne Indywidualna Specjalistyczna Praktyka Lekarska lek.med. Barbara Bazela
  • Poznan, Poland, 61-397
    • Prywatna Praktyka Lekarska Prof. UM dr Hab. Med. Pawel Hrycaj
  • Poznan, Poland, 60-218
    • Medyczne Centrum Hetmanska - Indywidualna Specjalistyczna Praktyka Lekarska -
  • Warszawa, Poland, 02-507
    • Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych
• Puerto Rico
  • Rio Piedras, Puerto Rico, 00935
    • University of Puerto Rico
  • San Juan, Puerto Rico, 00935
    • Division of Rheumatology, Allergy and Immunology
• Romania
  • Bucuresti, Romania, 20125
    • Spitalul Clinic Colentina
  • Bucuresti, Romania, 11172
    • Spitalul Clinic Sf. Maria
  • Cluj Napoca, Romania, 400006
    • Spitalul Clinic Jedetean de urgenta Cluj, Reumatologie
  • Galati, Romania, 800578
    • Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei"
• Taiwan
  • Taipei TOC, Taiwan, 100
    • National Taiwan University Hospital
• United States
  • Alabama
    • Anniston, Alabama, United States, 36207
      • Pinnacle Research Group, LLC
    • Anniston, Alabama, United States, 36207
      • Anniston Medical Clinic, PC
    • Birmingham, Alabama, United States, 35216
      • Achieve Clinical Research, LLC
  • California
    • Fair Oaks, California, United States, 95628
      • Med Investigations, Inc.
    • Lakewood, California, United States, 90712
      • Premier Clinical Research, LLC
    • Long Beach, California, United States, 90813
      • Novo Research
    • Long Beach, California, United States, 90813
      • St Mary Medical Center
    • Los Angeles, California, United States, 90048
      • Cedars-Sinai Medical Center
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
    • Los Angeles, California, United States, 90048
      • Wallace Rheumatic Study Center
    • Los Angeles, California, United States, 90095-6984
      • Ronald Reagan UCLA Medical Center
    • Los Angeles, California, United States, 90095-1670
      • UCLA Division of Rheumatology
    • Los Angeles, California, United States, 90095-1670
      • UCLA Rheumatology Clinical Research Center
    • Upland, California, United States, 91786
      • Inland Rheumatology Clinical Trials, Inc.
    • Upland, California, United States, 91786
      • Inland Rheumatology and Osteoporosis Medical Group
  • Florida
    • Daytona Beach, Florida, United States, 32114
      • Asthma, Allergy, Arthritis and Lung Center
    • Gainesville, Florida, United States, 32607
      • Southeastern Arthritis Center
    • Gainesville, Florida, United States, 32607
      • Southeastern Integrated Medical, PL, d/b/a Florida Medical Research Institute
    • Gainesville, Florida, United States, 32607
      • Southeastern Community Pharmacy
    • Gainesville, Florida, United States, 32607
      • Southeastern lmaging & Diagnostics
    • Miami, Florida, United States, 33175
      • New Horizon Research Center
    • Orlando, Florida, United States, 32804
      • Arthritis Associates
    • Ormond Beach, Florida, United States, 32174
      • Millennium Research
    • Palm Harbor, Florida, United States, 34684
      • The Arthritis Center
    • Pinellas Park, Florida, United States, 33781
      • Advent Clinical Research Centers, Inc.
    • Tampa, Florida, United States, 33614
      • Burnette & Silverfield, MDS PLC
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University
    • Atlanta, Georgia, United States, 30303
      • Grady Health Systems
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Idaho Arthritis Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Granger, Indiana, United States, 46530
      • Beacon Medical Group Rheumatology
    • Indianapolis, Indiana, United States, 46202
      • Indiana CTSI Clinical Research Center
    • Indianapolis, Indiana, United States, 46202
      • Investigational Drug Services
  • Maryland
    • Baltimore, Maryland, United States, 21205
      • Johns Hopkins University School of Medicine
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Outpatient Center
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Outpatient Express Testing Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02111
      • Tufts Medical Center/ Center for Arthritis and Rheumatic Diseases
  • Michigan
    • Ann Arbor, Michigan, United States, 48109-5422
      • University of Michigan Health System
    • Ann Arbor, Michigan, United States, 48109-5008
      • University of Michigan
    • Ann Arbor, Michigan, United States, 48109-5872
      • University of Michigan Health System,
    • Detroit, Michigan, United States, 48201-3450
      • Henry Ford Health System (Henry Ford Medical Center)
    • Saint Clair Shores, Michigan, United States, 48081
      • Shores Rheumatology P.C
  • Nevada
    • Las Vegas, Nevada, United States, 89102
      • University of Nevada School of Medicine
  • New Mexico
    • Albuquerque, New Mexico, United States, 87102
      • Albuquerque Clinical Trials
  • New York
    • Brooklyn, New York, United States, 11201
      • Arthritis and Osteoporosis Medical Associates, PLLC
    • Manhasset, New York, United States, 11030
      • Feinstein Institute for Medical Research
    • New York, New York, United States, 10016
      • NYU Center for Musculoskeletal Care
    • Rochester, New York, United States, 14623
      • Allergy/Immunology and Rheumatology
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • The University of North Carolina at Chapel Hill
    • Chapel Hill, North Carolina, United States, 27514
      • The University of North Carolina Clinical and Translational Research Center
    • Chapel Hill, North Carolina, United States, 27514
      • The University of North Carolina Hospitals Investigational Drug Services
    • Charlotte, North Carolina, United States, 28210
      • Box Arthritis & Rheumatology of the Carolinas, PLLC
    • Charlotte, North Carolina, United States, 28204
      • Joint and Muscle Medical Care
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Middleburg Heights, Ohio, United States, 44130
      • Paramount Medical Research and Consulting, Llc
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Oklahoma Medical Research Foundation
  • Pennsylvania
    • Wyomissing, Pennsylvania, United States, 19610
      • Clinical Research Center of Reading, LLP
  • South Carolina
    • Charleston, South Carolina, United States, 29406
      • Low Country Rheumatology, PA/Low Country Research
  • Tennessee
    • Jackson, Tennessee, United States, 38305
      • Arthritis Clinic
    • Jackson, Tennessee, United States, 38305
      • West Tennessee Research Institute
  • Texas
    • Dallas, Texas, United States, 75390
      • UT Southwestern Medical Center
    • Dallas, Texas, United States, 75390-8577
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77034
      • Accurate Clinical Research, Inc.
    • Houston, Texas, United States, 77004
      • Rheumatic Disease Clinical Research Center, LLC
    • Mesquite, Texas, United States, 75150
      • SouthWest Rheumatology Research, LLC
  • Washington
    • Seattle, Washington, United States, 98133
      • The Seattle Arthritis Clinic
    • Tacoma, Washington, United States, 98405
      • Tacoma Center for Arthritis Research, PS
  • West Virginia
    • Clarksburg, West Virginia, United States, 26301
      • Mountain State Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects between ages of 18 and 75 years old at time of signing consent.
• Have a clinical diagnosis of SLE according to 1997 update on the revised 1982 American College of Rheumatology (ACR) criteria.
• Have a unequivocally positive anti-nuclear antibody (ANA) test result.
• Active disease at screening defined by both: SLEDAI-2K score greater than or equal to 6 and BILAG Level A disease in more than or equal to 1 organ system (except renal or central nervous system) or BILAG B disease in more than or equal to 2 organ systems if no level A disease in present.

Exclusion Criteria:

• Any prior history of treatment with PF-04236921, or anti-IL-6 agent;
• Have received any of the following within 364 days of day 1: a biologic investigational agent other than B cell targeted therapy; required 3 or more courses of systemic corticosteroids for concomitant conditions; history of previously untreated or current evidence of active or untreated latent infection with Tuberculosis (TB), evidence of prior untreated or currently active TB by chest radiography, residing with or frequent close contact with an individual with active TB.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Placebo	Biological: PF-04236921; subcutaneous injection; administered at day 1, weeks 8, 16.; Biological: PF-04236921; subcutaneous injection; administered at day 1, weeks 8, 16
Other: 10 mg of PF-04236921	Biological: PF-04236921; subcutaneous injection; administered at day 1, weeks 8, 16.; Biological: PF-04236921; subcutaneous injection; administered at day 1, weeks 8, 16
Other: 50 mg of PF-04236921	Biological: PF-04236921; subcutaneous injection; administered at day 1, weeks 8, 16.; Biological: PF-04236921; subcutaneous injection; administered at day 1, weeks 8, 16
Other: 200 mg of PF-04236921	Biological: PF-04236921; subcutaneous injection; administered at day 1, weeks 8, 16.; Biological: PF-04236921; subcutaneous injection; administered at day 1, weeks 8, 16

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24	SRI components include:Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K),British Isles Lupus Assessment Group(BILAG) 2004,Physician's Global Assessment(PhGA).Participants classified as responder if they did not meet definition of treatment failure and met all the following criteria: greater than or equal to(>=) 4 point reduction in SLEDAI-2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; no worsening (less than [<] 0.3 point increase) in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. SLEDAI-2K:assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG:assesses disease extent, severity (range: A[severe] to E[no disease]). PhGA: assesses worsening in participant's general health status(range: 0[none] to 3[severe]).	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, and 20	SRI components include:SLEDAI-2K ,BILAG 2004, PhGA. Participants classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI-2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; no worsening (<0.3 point increase) in PhGA score. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial drug, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. SLEDAI-2K: assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). BILAG:assesses disease extent, severity (range: A [severe] to E [no disease]). PhGA: assesses worsening in participant's general health status(range: 0[none] to 3[severe]).	Week 4, 8, 12, 16, 20
Percentage of Participants Achieving Modified Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, 20, and 24	SRI components include: modified SLEDAI-2K (SLEDAI-2K without standard parameters "Low complement" and "Leukopenia"), BILAG 2004, PhGA. Participants classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI-2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; no worsening (<0.3 point increase) in PhGA score. Treatment failure: any new/increased use of corticosteroids, immunosuppressants/antimalarial drug, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. Modified SLEDAI-2K: assesses improvement in disease activity (range: 0 to 102; higher score = higher severity). BILAG: assesses disease extent, severity (range: A [severe] to E [no disease]). PhGA: assesses worsening in participant's general health status (range: 0[none] to 3[severe]).	Week 4, 8, 12, 16, 20, 24
Percentage of Participants Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response at Week 4, 8, 12, 16, 20, and 24	BICLA include: BILAG-2004, SLEDAI-2K, PhGA of disease activity. Participants classified as responder if they did not meet the definition of treatment failure and met all the following criteria: BILAG-2004 improvement (all A scores at baseline improved to B/C/D and all B scores improved to C or D); no worsening in disease activity (no new BILAG-2004 A scores or =<1 new B score); no worsening of total SLEDAI-2K score; no significant deterioration (<10 percent [%] worsening) in analogue PhGA. Treatment failure: any new/increased use of corticosteroids,immunosuppressants/antimalarial, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. BILAG:assesses disease extent, severity (range: A[severe] to E[no disease]). SLEDAI-2K:assesses improvement in disease activity (range: 0 to 105; higher score = higher severity). PhGA: assesses worsening in participant's general health status(range: 0[none] to 3[severe]).	Week 4, 8, 12, 16, 20, 24
Percentage of Participants Achieving Pre-defined Criteria for Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Components at Week 24	SRI components include: SLEDAI-2K, BILAG 2004 and PhGA. Participants classified as responder if they did not meet definition of treatment failure and met all the following criteria: >=4 point reduction in SLEDAI-2K score; no new BILAG A organ domain score or 2 new BILAG B organ domain scores; no worsening(<0.3 point increase) in PhGA score. Treatment failure: any new/increased use of corticosteroids, immunosuppressants/antimalarial drug, any death, hospitalization/treatment discontinuation due to SLE, any flare of lupus interfering with participation in study. SLEDAI-2K: assesses improvement in disease activity(range: 0 to 105; higher score = higher severity). BILAG: assesses disease extent, severity (range: A[severe] to E [no disease]). PhGA: assesses worsening in participant's general health status (range: 0[none] to 3[severe]). Model percent estimates reported only for 'Reduction in SLEDAI Score','No Worsening in PhGA' categories; for remaining categories, raw percentages reported	Week 24
Number of Participants With Clinically Significant Laboratory Tests Results	Pre-defined criteria were established for each laboratory test to define the values that would be identified as of potential clinical importance. Laboratory values included Alanine Aminotransferase (ALT) [>5.0 - 10.0*Upper limit of normal range (ULN)], Albumin [<26-20 gram per liter (g/L)/ <20 g/L], Amylase [>2.0 - 5.0*ULN], Aspartate Aminotransferase (AST) [>5.0 - 10.0*ULN], Creatine Kinase (CK) [>5.0 - 10.0* ULN/ >10.0*ULN], Glucose (Hyperglycemia) [>13.9 - 27.8 millimoles/liter (mmol/L)], Hemoglobin (HGB) [<80 - 65 g/L/ <65 g/L], Lipase [>2.0 - 5.0*ULN], Lymphocytes (Lymph.)(Absolute [Abs]) [<0.5 - 0.2*10^3/microliter (UL)/ <0.2*10^3/UL], Platelets [<50-25*10^3/UL/ <25*10^3/UL], potassium (low) [<3.0 - 2.5 mmol/L], Sodium (low) [<130 - 120 mmol/L], Total Neutrophils (TN) (Abs) [<1.0 - 0.5*10^3/UL/ <0.5*10^3/UL], Triglycerides [>5.7 - 11.4 mmol/L], White Blood Cell Count (WBC) [<2.0 - 1.0*10^3/UL/ <1.0*10^3/UL].	Baseline up to Week 52
Number of Participants Who Discontinued Due to Adverse Events	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Number of participants who discontinued due to adverse events were reported.	Baseline up to Week 52
Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. Number of participants with treatment-emergent AEs or SAEs (excluding infectious AEs or SAEs and injection site reactions) were reported. AEs include both SAEs and non-SAEs.	Baseline up to Week 52
Number of Participants With Treatment-Emergent Infectious Adverse Events (AEs) or Serious Adverse Events (SAEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent are events between first dose of study drug and up to Week 52 that were absent before treatment or that worsened relative to pretreatment state. Number of participants with treatment-emergent infectious AEs or SAEs were reported. AEs include both SAEs and non-SAEs.	Baseline up to Week 52
Number of Participants With Potentially Clinically Important (PCI) Electrocardiogram (ECG) Findings	Criteria for potentially clinically important (PCI) findings in ECG were defined as: heart rate <=40 beats per minute (bpm) or >=120 bpm; PR interval >=220 millisecond (msec); QT interval >=480 msec; QRS interval >=120 msec; QT interval corrected using the Fridericia formula (QTcF) >=500msec; no sinus rhythm.	Baseline up to Week 52
Number of Participants With Potentially Clinically Important Vital Signs Findings	Criteria for PCI findings in vital signs were defined as: sitting systolic blood pressure (Increase from baseline >=20 millimeter of mercury (mm Hg) and >=160 mm Hg or a decrease from baseline >=20 mm Hg and <=90 mm Hg) and sitting diastolic blood pressure (increase from baseline >=15 mm Hg and >=90 mm Hg or decrease from baseline >=15 mm Hg and <=60 mm Hg), pulse rate (increase from baseline >=15 beats/min and >=120 beats/min or decrease from baseline >=15 beats/min and <=50 beats /min), body temperature (increase of >=2 degree Fahrenheit (F) and temperature >=101 degree F) and weight (change of >=7% in body weight)	Baseline up to Week 52
Number of Participants With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (Nabs)	Human serum samples were analyzed for the presence or absence of anti-PF-04236921 antibodies. A positive ADA sample was further tested for neutralizing antibodies using a validated assay.	Baseline up to Week 52
Serum Concentration of PF-04236921	Serum PF-04236921 concentrations over time were summarized.	Day 1, Week 2, 4, 6, 8, 12, 16, 20, 24
Percentage of Participants With Corticosteroid Dose Reduced by Both Greater Than or Equal to (>=) 25 Percent (%) From Baseline and Less Than or Equal to (<=) 7.5 Milligrams Per Day (mg/Day)	Participants were given supplemental corticosteroids at baseline to control disease activity, if necessary. The steroid taper was based on participant's symptoms. Participants recorded their steroid usage on a diary card. Least Observation Carried Forward (LOCF) method was used to impute missing data.	Week 12, 16, 20, 24
Percentage of Participants With Normalized Serological Activity	Serologic activity was to be assessed in the subgroup of participants who had positive serologic activity at baseline.	Baseline up to Week 24
Patient Global Visual Analog Scale (VAS) Scores at Baseline	Participants assessed their disease activity using a 100 millimeter (mm) VAS. Participants answered the following question "Considering all the ways your disease affects you, how are you feeling today?" Response was recorded by placing a mark on the scale between 0 (very well) and 100 (extremely bad).	Baseline
Change From Baseline in Patient Global Visual Analog Scale (VAS) at Week 2, 4, 6, 8, 12, 16, 20 and 24	Participants assessed their disease activity using a 100 mm VAS. Participants answered the following question "Considering all the ways your disease affects you, how are you feeling today?" Response was recorded by placing a mark on the scale between 0 (very well) and 100 (extremely bad).	Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24
Change From Baseline in European Quality of Life 5 Dimensions Questionnaire (EQ-5D) at Week 4, 8, 12, 16, 20 and 24	EQ-5D is a standardized, participant-administered measure of health outcome. It provides a descriptive profile for 5 dimensions (mobility, self-care, usual activities, pain/discomfort, anxiety/depression), using 3 levels (no, moderate, or extreme problems) and a single index value characterizing current health status using a 100-point VAS (0= worst imaginable health state, 100= best imaginable health state).	Baseline, Week 4, 8, 12, 16, 20, 24
Thirty Six-Item Short-Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Baseline	SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as PCS and mental component score MCS. The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). LOCF method was used to impute missing values.	Baseline
Change From Baseline in 36-Item Short-Form Health Survey (SF-36) PCS and MCS at Week 4, 8, 12, 16, 20 and 24	SF-36 is a standardized survey evaluating 8 aspects of functional health and well-being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical component score (PCS) and mental component score (MCS). The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). LOCF method was used to impute missing values.	Baseline, Week 4, 8, 12, 16, 20, 24
Change From Baseline in Vitality Scores at Week 4, 8, 12, 16, 20 and 24	SF-36 is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. Vitality sub-score is a component of SF-36 Health Survey Questionnaire and assesses energy and fatigue. The vitality score ranged from 0-100 (100=highest level of functioning). LOCF method was used to impute missing values.	Baseline, Week 4, 8, 12, 16, 20, 24
Change From Baseline in Short Form-6 Dimension (SF-6D) at Week 4, 8, 12, 16, 20 and 24	The SF-6D focuses on seven of the eight health domains covered by the SF-36 Health Survey: physical functioning, role participation (combined role-physical and role-emotional), social functioning, bodily pain, mental health, and vitality. The SF-6D is an attempt to derive a single index from the SF-36 Health Survey for use in economic evaluation studies. As such, it represents a summary score based on a subset of the SF-36 data. Consequently, in lieu of the SF-6D, PCS and MCS SF-36 results are being provided. The score for each aspect and PCS/MCS is an average of the individual question scores, which are scaled 0-100 (100=highest level of functioning). LOCF method was used to impute missing values.	Baseline, Week 4, 8, 12, 16, 20, 24
Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Baseline	FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score).	Baseline
Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Week 4, 8, 12, 16, 20 and 24	FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated), greater was the participant's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the participant's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). LOCF method was used to impute missing values.	Baseline, Week 4, 8, 12, 16, 20, 24

Collaborators and Investigators

• Sponsor: Pfizer

Publications and helpful links

General Publications

• Li C, Shoji S, Beebe J. Pharmacokinetics and C-reactive protein modelling of anti-interleukin-6 antibody (PF-04236921) in healthy volunteers and patients with autoimmune disease. Br J Clin Pharmacol. 2018 Sep;84(9):2059-2074. doi: 10.1111/bcp.13641. Epub 2018 Jun 25.
• Wallace DJ, Strand V, Merrill JT, Popa S, Spindler AJ, Eimon A, Petri M, Smolen JS, Wajdula J, Christensen J, Li C, Diehl A, Vincent MS, Beebe J, Healey P, Sridharan S. Efficacy and safety of an interleukin 6 monoclonal antibody for the treatment of systemic lupus erythematosus: a phase II dose-ranging randomised controlled trial. Ann Rheum Dis. 2017 Mar;76(3):534-542. doi: 10.1136/annrheumdis-2016-209668. Epub 2016 Sep 26.

Helpful Links

• To obtain contact information for a study center near you, click here.

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2011
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: July 27, 2011
• First Submitted That Met QC Criteria: July 27, 2011
• First Posted (Estimate): July 29, 2011

Study Record Updates

• Last Update Posted (Actual): December 19, 2017
• Last Update Submitted That Met QC Criteria: December 18, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: safety; efficacy; multicenter; placebo-controlled; double-blind; dose-ranging; lupus.
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic
• Other Study ID Numbers: B0151006; 2011-000420-15 (EudraCT Number); Butterfly (Alias Study Number)