Clinical trial NCT01405196: Subcutaneous Treatment In Randomized Subjects To Evaluate Safety And Efficacy In Generalized Lupus Erythematosus
Official title: 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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lupus Erythematosus, Systemic
Keywords: double-blind
placebo-controlled
multicenter
dose-ranging
efficacy
safety
lupus.
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-07-29
Enrollment: 183
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants Achieving Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, and 20
timeFrame: Week 4, 8, 12, 16, 20
measure: Percentage of Participants Achieving Modified Systemic Lupus Erythematosus (SLE) Responder Index (SRI) at Week 4, 8, 12, 16, 20, and 24
timeFrame: Week 4, 8, 12, 16, 20, 24
measure: Percentage of Participants Achieving British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) Response at Week 4, 8, 12, 16, 20, and 24
timeFrame: Week 4, 8, 12, 16, 20, 24
measure: Percentage of Participants Achieving Pre-defined Criteria for Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Components at Week 24
timeFrame: Week 24
measure: Number of Participants With Clinically Significant Laboratory Tests Results
timeFrame: Baseline up to Week 52
measure: Number of Participants Who Discontinued Due to Adverse Events
timeFrame: Baseline up to Week 52
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 52
measure: Number of Participants With Treatment-Emergent Infectious Adverse Events (AEs) or Serious Adverse Events (SAEs)
timeFrame: Baseline up to Week 52
measure: Number of Participants With Potentially Clinically Important (PCI) Electrocardiogram (ECG) Findings
timeFrame: Baseline up to Week 52
measure: Number of Participants With Potentially Clinically Important Vital Signs Findings
timeFrame: Baseline up to Week 52
measure: Number of Participants With Anti-drug Antibodies (ADAs) and Neutralizing Antibodies (Nabs)
timeFrame: Baseline up to Week 52
measure: Serum Concentration of PF-04236921
timeFrame: Day 1, Week 2, 4, 6, 8, 12, 16, 20, 24
measure: 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)
timeFrame: Week 12, 16, 20, 24
measure: Percentage of Participants With Normalized Serological Activity
timeFrame: Baseline up to Week 24
measure: Patient Global Visual Analog Scale (VAS) Scores at Baseline
timeFrame: Baseline
measure: Change From Baseline in Patient Global Visual Analog Scale (VAS) at Week 2, 4, 6, 8, 12, 16, 20 and 24
timeFrame: Baseline, Week 2, 4, 6, 8, 12, 16, 20, 24
measure: Change From Baseline in European Quality of Life 5 Dimensions Questionnaire (EQ-5D) at Week 4, 8, 12, 16, 20 and 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20, 24
measure: Thirty Six-Item Short-Form Health Survey (SF-36) Physical Component Score (PCS) and Mental Component Score (MCS) at Baseline
timeFrame: Baseline
measure: Change From Baseline in 36-Item Short-Form Health Survey (SF-36) PCS and MCS at Week 4, 8, 12, 16, 20 and 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20, 24
measure: Change From Baseline in Vitality Scores at Week 4, 8, 12, 16, 20 and 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20, 24
measure: Change From Baseline in Short Form-6 Dimension (SF-6D) at Week 4, 8, 12, 16, 20 and 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20, 24
measure: Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Baseline
timeFrame: Baseline
measure: Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Week 4, 8, 12, 16, 20 and 24
timeFrame: Baseline, Week 4, 8, 12, 16, 20, 24
Other outcomes:
Locations:
city: Anniston
country: United States
facility: Anniston Medical Clinic, PC
state: Alabama
city: Anniston
country: United States
facility: Pinnacle Research Group, LLC
state: Alabama
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC
state: Alabama
city: Fair Oaks
country: United States
facility: Med Investigations, Inc.
state: California
city: Lakewood
country: United States
facility: Premier Clinical Research, LLC
state: California
city: Long Beach
country: United States
facility: Novo Research
state: California
city: Long Beach
country: United States
facility: St Mary Medical Center
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Los Angeles
country: United States
facility: Wallace Rheumatic Study Center
state: California
city: Los Angeles
country: United States
facility: UCLA Division of Rheumatology
state: California
city: Los Angeles
country: United States
facility: UCLA Rheumatology Clinical Research Center
state: California
city: Los Angeles
country: United States
facility: Ronald Reagan UCLA Medical Center
state: California
city: Los Angeles
country: United States
facility: UCLA Medical Center
state: California
city: Upland
country: United States
facility: Inland Rheumatology and Osteoporosis Medical Group
state: California
city: Upland
country: United States
facility: Inland Rheumatology Clinical Trials, Inc.
state: California
city: Daytona Beach
country: United States
facility: Asthma, Allergy, Arthritis and Lung Center
state: Florida
city: Gainesville
country: United States
facility: Southeastern Arthritis Center
state: Florida
city: Gainesville
country: United States
facility: Southeastern Community Pharmacy
state: Florida
city: Gainesville
country: United States
facility: Southeastern Integrated Medical, PL, d/b/a Florida Medical Research Institute
state: Florida
city: Gainesville
country: United States
facility: Southeastern lmaging & Diagnostics
state: Florida
city: Miami
country: United States
facility: New Horizon Research Center
state: Florida
city: Orlando
country: United States
facility: Arthritis Associates
state: Florida
city: Ormond Beach
country: United States
facility: Millennium Research
state: Florida
city: Palm Harbor
country: United States
facility: The Arthritis Center
state: Florida
city: Pinellas Park
country: United States
facility: Advent Clinical Research Centers, Inc.
state: Florida
city: Tampa
country: United States
facility: Burnette & Silverfield, MDS PLC
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Grady Health Systems
state: Georgia
city: Meridian
country: United States
facility: Idaho Arthritis Center
state: Idaho
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Granger
country: United States
facility: Beacon Medical Group Rheumatology
state: Indiana
city: Indianapolis
country: United States
facility: Indiana CTSI Clinical Research Center
state: Indiana
city: Indianapolis
country: United States
facility: Investigational Drug Services
state: Indiana
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Outpatient Center
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Outpatient Express Testing Center
state: Maryland
city: Boston
country: United States
facility: Tufts Medical Center/ Center for Arthritis and Rheumatic Diseases
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Health System
state: Michigan
city: Ann Arbor
country: United States
facility: University of Michigan Health System,
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System (Henry Ford Medical Center)
state: Michigan
city: Saint Clair Shores
country: United States
facility: Shores Rheumatology P.C
state: Michigan
city: Las Vegas
country: United States
facility: University of Nevada School of Medicine
state: Nevada
city: Albuquerque
country: United States
facility: Albuquerque Clinical Trials
state: New Mexico
city: Brooklyn
country: United States
facility: Arthritis and Osteoporosis Medical Associates, PLLC
state: New York
city: Manhasset
country: United States
facility: Feinstein Institute for Medical Research
state: New York
city: New York
country: United States
facility: NYU Center for Musculoskeletal Care
state: New York
city: Rochester
country: United States
facility: Allergy/Immunology and Rheumatology
state: New York
city: Chapel Hill
country: United States
facility: The University of North Carolina Clinical and Translational Research Center
state: North Carolina
city: Chapel Hill
country: United States
facility: The University of North Carolina Hospitals Investigational Drug Services
state: North Carolina
city: Chapel Hill
country: United States
facility: The University of North Carolina at Chapel Hill
state: North Carolina
city: Charlotte
country: United States
facility: Joint and Muscle Medical Care
state: North Carolina
city: Charlotte
country: United States
facility: Box Arthritis & Rheumatology of the Carolinas, PLLC
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Middleburg Heights
country: United States
facility: Paramount Medical Research and Consulting, LLC
state: Ohio
city: Oklahoma City
country: United States
facility: Oklahoma Medical Research Foundation
state: Oklahoma
city: Wyomissing
country: United States
facility: Clinical Research Center of Reading, LLP
state: Pennsylvania
city: Charleston
country: United States
facility: Low Country Rheumatology, PA/Low Country Research
state: South Carolina
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: UT Southwestern Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Rheumatic Disease Clinical Research Center, LLC
state: Texas
city: Houston
country: United States
facility: Accurate Clinical Research, Inc.
state: Texas
city: Mesquite
country: United States
facility: Southwest Rheumatology Research, LLC
state: Texas
city: Seattle
country: United States
facility: The Seattle Arthritis Clinic
state: Washington
city: Tacoma
country: United States
facility: Tacoma Center for Arthritis Research, PS
state: Washington
city: Clarksburg
country: United States
facility: Mountain State Clinical Research
state: West Virginia
city: La Plata
country: Argentina
facility: Framingham Centro Medico
state: Buenos Aires
city: Rosario
country: Argentina
facility: Instituto CAICI S.R.L.
state: Santa FE
city: San Miguel de Tucuman
country: Argentina
facility: Centro Medico Privado de Reumatologia
state: Tucuman
city: C.a.b.a
country: Argentina
facility: Centro de Educación Medica e Investigaciones Clinicas "Norberto Quirno" CEMIC
city: San Juan
country: Argentina
facility: Centro Polivalente de Asistencia e Investigación Clínica - CER- San Juan
city: Santiago
country: Chile
facility: Sociedad Medica del Aparato Locomotor S.A. (SOMEAL)
state: Region Metropolitana
city: Santiago
country: Chile
facility: Centro de Estudios Reumatologicos
state: RM
city: Santiago
country: Chile
facility: Centro Medico Prosalud
state: RM
city: Envigado
country: Colombia
facility: Mix Supplier S.A.
state: Antioquia, Colombia
city: Envigado
country: Colombia
facility: Centro Integral de Reumatologia REUMALAB S.A.S.
state: Antioquia
city: Medellin
country: Colombia
facility: Hospital Pablo Tobon Uribe
state: Antioquia
city: Barranquilla
country: Colombia
facility: Centro Integral de Reumatología del Caribe CIRCARIBE SAS
state: Atlantico
city: Barranquilla
country: Colombia
facility: Congregacion de Hermanas Franciscanas Misioneras de Maria Auxiliadora- Clinica Asunción
state: Atlantico
city: Barranquilla
country: Colombia
facility: Organizacion Clinica General del Norte S.A.
state: Atlantico
city: Bogota, Distrito Capital
country: Colombia
facility: Farmamix Ltda.
state: Cundimarca
city: Bogota
country: Colombia
facility: Centro Integral de Reumatologia e Inmunologia S.A.S.- CIREI S.A.S.
state: Cundinamarca
city: Bogota
country: Colombia
facility: Riesgo De Fractura S.A
state: Cundinamarca
city: Bucaramanga
country: Colombia
facility: Servimed E.U
state: Santander
city: Bogota
country: Colombia
facility: Farmamix Ltda.
city: Berlin
country: Germany
facility: Charité - Universitaetsmedizin Berlin
city: Berlin
country: Germany
facility: Charité University Medicine Berlin. Schlosspark-Klinik
city: Erlangen
country: Germany
facility: Universitaetsklinikum Erlangen
city: Frankfurt/Main
country: Germany
facility: CIRI am Klinikum der Goethe-Universitaet
city: Koeln
country: Germany
facility: Universitaetsklinikum Koeln
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig AoeR, Department fuer Innere Medizin
city: Budapest
country: Hungary
facility: Qualiclinic Kft.
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Orvos és Egeszsegtudomanyi Centrum
city: Gyula
country: Hungary
facility: Bekes Megyei Kepviselo-testulet Pandy Kalman Korhaz Infektologia, Hepatologia es Immunologia
city: Busan
country: Korea, Republic of
facility: Dong-A University Medical Center 1
city: Chisinau
country: Moldova, Republic of
facility: Spitalul Clinic Republican
state: Md-2025
city: San Isidro
country: Peru
facility: Centro de Investigacion REUMED, Clinica Anglo Americana
state: Lima
city: Santiago de Surco
country: Peru
facility: Investigaciones Clínicas SAC
state: Lima
city: Surco
country: Peru
facility: Investigaciones Clinicas SAC
state: Lima
city: Arequipa
country: Peru
facility: Unidad de Investigación en Medicina Interna y Enfermedades Críticas
city: Elblag
country: Poland
facility: NZOZ Centrum Reumatologiczne Indywidualna Specjalistyczna Praktyka Lekarska lek.med. Barbara Bazela
city: Poznan
country: Poland
facility: Medyczne Centrum Hetmanska - Indywidualna Specjalistyczna Praktyka Lekarska -
city: Poznan
country: Poland
facility: Prywatna Praktyka Lekarska Prof. UM Dr hab. med. Pawel Hrycaj
city: Warszawa
country: Poland
facility: Centralny Szpital Kliniczny Ministerstwa Spraw Wewnetrznych
city: Rio Piedras
country: Puerto Rico
facility: University of Puerto Rico
city: San Juan
country: Puerto Rico
facility: Division of Rheumatology, Allergy and Immunology
city: Bucuresti
country: Romania
facility: Spitalul Clinic Sf. Maria
city: Bucuresti
country: Romania
facility: Spitalul Clinic Colentina
city: Cluj Napoca
country: Romania
facility: Spitalul Clinic Jedetean de urgenta Cluj, Reumatologie
city: Galati
country: Romania
facility: Spitalul Clinic Judetean de Urgenta "Sf. Apostol Andrei"
city: Taipei TOC
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.