Abatacept in the Treatment and Prevention of Active Systemic Lupus Erythematosus (SLE) Flares in Combination With Prednisone

A Phase IIB, Multi-Center, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Abatacept vs Placebo on a Background of Oral Glucocorticosteroids in the Treatment of Subjects With Systemic Lupus Erythematosus and the Prevention of Subsequent Lupus Flares

The purpose of this clinical research study is to learn whether Abatacept can treat and prevent lupus flares; specifically, in patients with active lupus flares in at least one of three organ systems: skin (discoid lesions); inflammation of the lining of the heart (pericarditis), or inflammation of the lining of the lung (pleuritis/pleurisy); or inflammation of more than 4 joints (arthritis). All participants will receive prednisone or prednisone-equivalent treatment in combination with study medication. The safety of this treatment will also be studied.

Study Overview

• Status: Completed
• Conditions: Systemic Lupus Erythematosus
• Intervention / Treatment: Drug: Abatacept; Drug: Prednisone; Drug: Abatacept; Drug: Placebo

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

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Cairns, Queensland, Australia, 4870
      • Local Institution
    • Maroochydore, Queensland, Australia, 4558
      • Local Institution
  • Victoria
    • Clayton, Victoria, Australia, 3168
      • Local Institution
    • Heidelberg, Victoria, Australia, 3084
      • Local Institution
    • Malvern, Victoria, Australia, 3144
      • Local Institution
• Austria
  • Graz, Austria, 8036
    • Local Institution
• Belgium
  • Bruxelles, Belgium, 1200
    • Local Institution
  • Leuven, Belgium, 3000
    • Local Institution
• Brazil
  • Sao Paulo, Brazil, 01246
    • Local Institution
  • Sao Paulo, Brazil, 04023900
    • Local Institution
  • Sao Paulo, Brazil, 04233
    • Local Institution
  • Goias
    • Goiania, Goias, Brazil, 74050
      • Local Institution
  • Parana
    • Curitiba, Parana, Brazil, 80060
      • Local Institution
  • Rio De Janeiro
    • Rio De Janeiro - Rj, Rio De Janeiro, Brazil, 20551
      • Local Institution
  • Sao Paulo
    • Campinas, Sao Paulo, Brazil, 13083
      • Local Institution
    • São Paulo, Sao Paulo, Brazil, 04027
      • Local Institution
• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1L7
      • Local Institution
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3A 1M4
      • Local Institution
• France
  • Bordeaux Cedex, France, 33076
    • Local Institution
  • Montpellier Cedex 5, France, 34295
    • Local Institution
  • Paris Cedex 14, France, 75679
    • Local Institution
• Germany
  • Berlin, Germany, 13125
    • Local Institution
  • Duesseldorf, Germany, 40225
    • Local Institution
  • Freiburg, Germany, 79106
    • Local Institution
• Italy
  • Ferrara, Italy, 44100
    • Local Institution
• Korea, Republic of
  • Seoul, Korea, Republic of, 110-744
    • Local Institution
  • Seoul, Korea, Republic of, 137-040
    • Local Institution
  • Seoul, Korea, Republic of, 138-736
    • Local Institution
  • Sungdong-Gu
    • Seoul, Sungdong-Gu, Korea, Republic of, 133-792
      • Local Institution
• Mexico
  • Aguascalientes, Mexico, 20000
    • Local Institution
  • Distrito Federal
    • Mexico City, Distrito Federal, Mexico, 06726
      • Local Institution
  • Michioacan
    • Morelia, Michioacan, Mexico, 58070
      • Local Institution
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Local Institution
• South Africa
  • Kwa Zulu Natal
    • Berea, Kwa Zulu Natal, South Africa, 4001
      • Local Institution
  • Western Cape
    • Panorama, Western Cape, South Africa, 7506
      • Local Institution
• Taiwan
  • Kaohsiung, Taiwan, 833
    • Local Institution
  • Taichung, Taiwan, 407
    • Local Institution
  • Taipei, Taiwan, 105
    • Local Institution
  • Taipei, Taiwan, 11217
    • Local Institution
• United Kingdom
  • Greater London
    • London, Greater London, United Kingdom, SE1 7EX
      • Local Institution
• United States
  • Arizona
    • Tucson, Arizona, United States, 85724
      • University of Arizona Arthritis Center
  • California
    • Long Beach, California, United States, 90808
      • Office Of Geoffrey S. Dolan, Md
    • Los Angeles, California, United States, 90048
      • 8737 Beverly Blvd.
  • Colorado
    • Denver, Colorado, United States, 80230
      • Denver Arthritis Clinic
  • Florida
    • Ft. Lauderdale, Florida, United States, 33334
      • CRIA Research
  • Illinois
    • Chicago, Illinois, United States, 60637
      • The University of Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Kentuckiana Center for Better Bone and Joint Health
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Kelly, Timothy
  • New York
    • Brooklyn, New York, United States, 11203
      • SUNY downstate Medical Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Ok Medical Research Foundations
  • Texas
    • Sugarland, Texas, United States, 77479
      • Texas Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• participants must be diagnosed with SLE and be experiencing an active lupus flare in at least one of three organ systems: skin (discoid lesions), inflammation of the lining of the heart (pericarditis), or inflammation of the lining of the lung (pleuritis/pleurisy); or inflammation of more than 4 joints within 14 days of a screening visit (arthritis)
• Stable dose of prednisone (<30mg) for at least one month

Exclusion Criteria:

• participants experiencing an active lupus flare in the kidney or central nervous systems
• Treatment with a stable dose of azathioprine, mycophenolate mofetil, hydroxychloroquine, chloroquine, or methotrexate for less than three months prior to the study
• participants with active viral or bacterial infections
• participants with any other autoimmune disease as a main diagnosis
• Prior treatment with rituximab

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Abatacept + Prednisone; Double Blind Period	Drug: Abatacept; Injectable, intravenous, 10 mg/kg, abatacept every 28 days, 12 months; Other Names: Orencia; Drug: Prednisone; Tablets, oral, 30 mg, daily for 28 days then taper off, 12 months; Drug: Abatacept; Injectable, intravenous, 10 mg/kg, every 28 days; Other Names: Orencia
PLACEBO_COMPARATOR: Placebo + Prednisone; Double Blind Period	Drug: Prednisone; Tablets, oral, 30 mg, daily for 28 days then taper off, 12 months; Drug: Placebo; Injectable, intravenous, 0 mg, every 28 days, 12 months
EXPERIMENTAL: Abatacept; Open Label	Drug: Abatacept; Injectable, intravenous, 10 mg/kg, abatacept every 28 days, 12 months; Other Names: Orencia; Drug: Abatacept; Injectable, intravenous, 10 mg/kg, every 28 days; Other Names: Orencia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Double Blind Period (DB); Number of Participants Experiencing a New SLE Flare	SLE flares scored using BILAG:A:presence of =>1 serious;B:more moderate;C:mild symptomatic;D:prior activity,no current symptoms;E:organ that has never been involved. Calculated based on change during previous 4 weeks (1=improving,2=staying same,3=worsening,4=new).New SLE flare:first BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and start of prednisone/prednisone-equivalent taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).	From start of corticosteroid taper to Day 365
Open Label Period (OL); Number of Participants Who Died, Experienced Adverse Events (AEs), Serious AEs, Drug Related AEs or SAEs and Discontinued Due to AEs	AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Participants who discontinued the study due to an AE were recorded. Drug-related AEs or SAEs: events with a relationship to the study therapy of certain; probable; possible; or missing.	From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
OL; Number of Participants With Significant AEs of Special Interest	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, it was decided that AEs of particular importance were associated with the use of immunomodulatory agents. Number of participants with infections, malignant Neoplasms, pre-specified autoimmune disorders, acute-infusional AEs and peri-infusional AEs were recorded.	From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
OL; Number of Participants With Marked Abnormalities (MAs) in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count	MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Hemoglobin: >3 g/dL decrease from pre-treatment (pre-Rx) value; hematocrit: <0.75* pre-Rx value; erythrocyte count: <0.75* pre-Rx value; platelet count: <0.67* lower limit of normal (LLN) or >1.5* upper limit of normal (ULN) (or, if pre-Rx value <LLN, then <0.5* pre-Rx value or <100000/mm^3).	From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
OL; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)	MMAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Leukocytes: <0.75* LLN or >1.25* ULN (or, if pre-Rx value <LLN, then <0.8* pre-Rx or >ULN. If pre-Rx value >ULN, then >1.2* pre-Rx or <LLN; Neutrophils+bands (absolute): <1.00* 10^3 cells/microliter (c/uL); Lymphocytes (absolute): <0.75* 10^3 c/uL or >7.50* 10^3 c/uL; Monocytes (absolute): >2000/mm^3; Basophils (absolute): >0.40* 10^3 c/uL; Eosinophils (absolute): >0.75* 10^3 c/uL.	From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
OL; Number of Participants With MAs in Serum Chemistry: Alkaline Phosphatase (ALP), Aspartate-aminotransferase (AST), Alanine-aminotransferase (ALT), Gamma-glutamyl Transferase (GGT), Bilirubin(Total), Blood Urea Nitrogen (BUN), Creatinine	MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. ALP, GGT: >2* ULN (if pre-Rx >ULN, then >3* pre-Rx); AST, ALT: >3* ULN (if pre-Rx >ULN, then >4* pre-Rx). Bilirubin (total): >2* ULN (if pre-Rx >ULN, then >4* pre-Rx), BUN:>2* pre-Rx; Creatinine:>1.5* pre-Rx.	From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
OL; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total), Protein (Total)	MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Sodium (serum): <0.95x LLN or >1.05x ULN (if pre-Rx<LLN, then <0.95x pre-Rx or >ULN. If pre-Rx >ULN, then >1.05x pre-Rx or <LLN); Potassium (serum), Chloride (serum), protein (total): <0.9x LLN or >1.1xULN (if pre-Rx <LLN, then <0.9xpre-Rx or >ULN. If pre-Rx >ULN, then >1.1xpre-Rx or <LLN; Calcium (total): <0.8xLLN or >1.2xULN (if pre-Rx <LLN, then <0.75x pre-Rx or >ULN. If pre-Rx >ULN, then >1.25x pre-Rx or <LLN.	From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
OL; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides	MAs are laboratory measurements marked as abnormal, as per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Glucose: <65 mg/dL or >220 mg/dL; Glucose (fasting serum): <0.8* LLN or >1.5 ULN (if pre-Rx <LLN, then <0.8* pre-Rx or >ULN. If pre-Rx >ULN, then >2.0* pre-Rx or <LLN; Albumin: <0.9* LLN (if pre-Rx <LLN, then <0.75 * pre-Rx); cholesterol (total): >2* pre-Rx; triglycerides: >=2.5* ULN, or if pre Rx>ULN then use >2.5* pre Rx; fasting triglycerides: >=2.0* ULN, or if pre Rx>ULN then use >2.0* pre Rx.	From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period
OL; Number of Participants With MAs in Urinalysis	MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following definitions specify the criteria for MAs in urinalysis, Protein, glucose, blood, Leukocyte esterase, red blood cells (RBC), white blood cells (WBC): >=2+ (or, if value >=4, or if pre-Rx value = 0 or 0.5, then >= 2* or if pre-Rx value =1, then >=3, or if pre-Rx = 2 or 3, then >=4); protein (24 hour urine): >1000 mg/24 hrs and >=2* pre-Rx; Glomerular filtration rate (GFR): <=60 mL/min/1.73m^2 or > 15% change from baseline; Protein/creatinine ratio: > 100 mg/mmol.	From start of study drug therapy in open-label period (Day 365) up to 56 days after the last dose of open-label period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DB; Number of Participants With a New SLE Flare During the Initial 6 Months	SLE flares scored using BILAG:A:presence of =>1 serious;B:more moderate;C:mild symptomatic;D:prior activity,no current symptoms;E:organ that has never been involved.Calculated based on change during previous 4 weeks (1=improving,2=staying same,3=worsening,4=new).New SLE flare:first BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and/or start of prednisone/prednisone-equivalent taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).	From start of corticosteroid taper to 6 months.
DB; Total Number of New SLE Flares Each Participant Experienced	SLE flares scored using BILAG:A:presence of =>1 serious;B:more moderate;C:mild symptomatic;D:prior activity,no current symptoms;E:organ that has never been involved.Calculated based on change during previous 4 weeks (1=improving,2=staying same,3=worsening,4=new).New SLE flare:BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and/or start of prednisone/prednisone-equivalent taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).	From start of corticosteroid taper to Day 365
DB; Median Number of Days to the First Occurrence of a New SLE Flare	Elapsed days between start of corticosteroid taper & first day of flare.Scored using BILAG:A:presence of =>1 serious;B:more moderate;C:mild symptomatic;D:prior activity,no current symptoms;E:organ that has never been involved.Calculated based on change during previous 4 weeks (1=improving,2=staying same,3=worsening,4=new).New SLE flare:first BILAG 'A' or 'B' event adjudicated to be flare following resolution of entry flare and/or start of corticosteroid taper.Inception treatment failure included (entry flare did not subside by Day 57/participant discontinued double-blind period before Day 29).	From start of corticosteroid taper to confirmation of disease flare or the end of double-blind period
DB; Number of Participants With a Change in the SLICC/ACR Damage Index at 1 Year Compared to Baseline	SLICC/ACR score or damage index is a measure of cumulative damage due to Systemic Lupus Erythematosus (SLE). Damage is defined as non-reversible change (not related to active inflammation) occurring since onset of lupus, ascertained by clinical assessment and present for at least 6 months. A score of 0=no damage, early damage is defined as ≥1. The total maximum score is 48, and increasing score indicates increasing disease severity.	From start of study drug treatment to Day 365
DB; Number of Participants Who Died, Experienced AEs, Other SAEs or Discontinuations Due to AEs, Drug Related AEs	AEs: any new untoward medical occurrences/worsening of pre-existing medical condition, whether or not related to study drug. SAE: any AE that resulted in death; was life threatening; resulted in persistent/significant disability/incapacity; resulted in/prolonged an existing in-patient hospitalization; was a congenital anomaly/birth defect; or was an overdose. Drug-related AEs: events with a certain; probable; possible; or missing relationship to the study therapy. Participants who discontinued the study due to an AE were recorded.	Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier
DB; Number of Participants With Significant AEs of Special Interest	An AE was defined as any new untoward medical occurrence or worsening of a pre-existing medical condition (even if not caused by the study drug). For this study, AEs of special interest were associated with the use of immunomodulatory agents. Number of participants with infections, malignant neoplasms, pre-specified autoimmune disorders, acute infusional AEs and peri-infusional AEs were recorded.	Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier
DB; Number of Participants With MAs in Hematology: Hemoglobin, Hematocrit, Erythrocytes and Platelet Count	MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Hemoglobin: >3 g/dL decrease from pre-treatment (pre-Rx) value; hematocrit: <0.75* pre-Rx value; erythrocyte count: <0.75* pre-Rx value; platelet count: <0.67* LLN or >1.5* ULN (or, if pre-Rx value <LLN, then <0.5* pre-Rx value or <100000/mm^3).	Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier
DB; Number of Participants With MAs in Hematology: Leukocytes, Neutrophils + Bands (Absolute), Lymphocytes (Absolute), Monocytes (Absolute), Basophils (Absolute) and Eosinophils (Absolute)	MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following hematology MA definitions specify the criteria for the data presented. Leukocytes: <0.75* LLN or >1.25* ULN (or, if pre-Rx value <LLN, then <0.8* pre-Rx or >ULN. If pre-Rx value >ULN, then >1.2* pre-Rx or <LLN; Neutrophils+bands (absolute): <1.00* 10^3 cells/microliter (c/uL); Lymphocytes (absolute): <0.75* 10^3 c/uL or >7.50* 10^3 c/uL; Monocytes (absolute): >2000/mm^3; Basophils (absolute): >0.40* 10^3 c/uL; Eosinophils (absolute): >0.75* 10^3 c/uL.	Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier
DB: Number of Participants With MAs in Serum Chemistry: ALP, AST, ALT, GGT, Bilirubin (Total), BUN and Creatinine	MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria. ALP, GGT: >2* ULN (if pre-Rx >ULN, then >3* pre-Rx); AST, ALT: >3* ULN (if pre-Rx >ULN, then >4* pre-Rx). Bilirubin (total): >2* ULN (if pre-Rx >ULN, then >4* pre-Rx), BUN:>2* pre-Rx; Creatinine:>1.5* pre-Rx.	Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier
DB; Number of Participants With MAs in Serum Chemistry: Sodium (Serum), Potassium (Serum), Chloride (Serum), Calcium (Total),Protein (Total)	MAs are laboratory measurements marked as abnormal as per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Sodium (serum): <0.95* LLN or >1.05* ULN (if pre-Rx <LLN, then <0.95* pre-Rx or >ULN. If pre-Rx >ULN, then >1.05* pre-Rx or <LLN); Potassium (serum), Chloride (serum), protein (total): <0.9* LLN or >1.1* ULN (if pre-Rx <LLN, then <0.9* pre-Rx or >ULN. If pre-Rx >ULN, then >1.1* pre-Rx or <LLN; Calcium (total): <0.8* LLN or >1.2* ULN (if pre-Rx <LLN, then <0.75* pre-Rx or >ULN. If pre-Rx >ULN, then >1.25* pre-Rx or <LLN.	Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier
DB; Number of Participants With MAs in Serum Chemistry: Glucose (Serum), Glucose (Fasting Serum), Albumin, Cholesterol (Total), Triglycerides, Fasting Triglycerides	MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following serum chemistry MA definitions specify MA criteria, Glucose: <65 mg/dl or >220 mg/dl; Glucose (fasting serum): <0.8* LLN or >1.5 ULN (if pre-Rx <LLN, then <0.8* pre-Rx or >ULN. If pre-Rx >ULN, then >2.0* pre-Rx or <LLN; Albumin: <0.9* LLN (if pre-Rx <LLN, then <0.75 * pre-Rx); cholesterol (total): >2* pre-Rx; triglycerides: >=2.5* ULN, or if pre Rx>ULN then use >2.5* pre Rx; fasting triglycerides: >=2.0* ULN, or if pre Rx>ULN then use >2.0* pre Rx.	Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier
DB; Number of Participants With MAs in Urinalysis	MAs are laboratory measurements marked as abnormal, per pre-defined study criteria, at any study time point. The following definitions specify the criteria for MAs in urinalysis, Protein, glucose, blood, Leukocyte esterase, RBC, WBC: >=2+ (or, if value >=4, or if pre-Rx value = 0 or 0.5, then >= 2* pre-Rx, or if pre-Rx value =1, then >=3, or if pre-Rx = 2 or 3, then >=4); protein (24 hour urine): >1000 mg/24 hrs and >=2* pre-Rx; GFR: <=60 mL/min/1.73m^2 or > 15% change from baseline; Protein/creatinine ratio: > 100 mg/mmol.	Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier
DB; Number of Participants With Clinically Significant Abnormal Vital Signs and/or Physical Examination Findings	Vital signs assessments and physical examination were conducted throughout the study. Vital signs assessments included body temperature, respiratory rate, blood pressure (systolic and diastolic) and heart rate. The investigator used his/her clinical judgment to decide whether or not abnormalities in vital signs or physical examination were clinically meaningful.	Events recorded at each participant encounter, from start of study drug therapy up to Day 337, including up to 56 days after the last dose or up to the first dose of open-label, whichever occurred earlier
DB; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment	Electrochemiluminescence (ECL) immunoassay based on Meso Scale Discovery (MSD) technology was used to detect antibodies specific for CTLA4-T and for abatacept.	From Day 1 to Day 365
OL; Number of Participants With a New SLE Flare	SLE flares scored using BILAG:A:presence of =>1 serious lupus features;B:more moderate features;C:mild symptomatic features;D:prior activity with no current symptoms due to active lupus;E:an organ that has never been involved.BILAG scores based on degrees of change in clinical features (1=improving,2=staying the same,3=worsening,4=new).New SLE flare means new BILAG A/B features in any organ system.Based on the recommendation of the Data Monitoring Committee, open-label period terminated, as failed to meet primary outcome measure for double-blind period/increase in SAEs in abatacept group.	From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729.
OL; Number of Participants With a Change in the SLICC/ACR Damage Index at Year 2 Compared to Baseline	SLICC/ACR damage index:measure of cumulative damage due to SLE.Damage=non-reversible change occurring since onset of lupus,ascertained by clinical assessment & present for =>6 months.Scores of SLICC/ACR index:1:single episode;2:repeated episodes at least 6 months apart.Change in score from baseline to 1 year presented as:no change,increase 1 (an increase in score of 1),increase >1 (an increase in score of >1).Based on recommendation of Data Monitoring Committee, open-label period terminated, as failed to meet primary outcome measure for double-blind period/increase in SAEs in abatacept group.	From start of study drug therapy in open-label period (Day 365) and on Day 729.
OL; Total Number of BILAG A Flares Each Participant Experienced	Total number of BILAG A flares in any organ system after steroid tapering = new BILAG A features in any organ system. Scores defined as follows: None: participants with no BILAG A flare; 1: participants with 1 BILAG A flare or participants who discontinued without a new BILAG A flare were imputed as having one event. 2: participants with 2 BILAG A flares; 3 or >3: participants with 3 or more BILAG A flares.Based on recommendation of Data Monitoring Committee, open-label period terminated, as failed to meet primary outcome measure for double-blind period/increase in SAEs in abatacept group.	From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729.
OL; Area Under the Curve (AUC) for Prednisone or Prednisone Equivalent	Total exposure to glucocorticosteroid was measured by the total prednisone or prednisone equivalent AUC. Based on the recommendation of the Data Monitoring Committee, the open-label, long-term extension period was terminated by the sponsor, for failure to meet the primary outcome measure for the double-blind period and because of an increase in SAEs in the abatacept treatment group. As such, these data were not analyzed.	From start of study drug therapy in open-label period (Day 365), Day 393, 421, 449 and every 28 days thereafter till Day 729.
OL; Number of Participants With Antibodies Specific for CTLA4-T and Abatacept, Following Abatacept Treatment	MSD technology was used to detect antibodies specific for CTLA4-T and for abatacept.	After the first dose of open-label period

Collaborators and Investigators

• Sponsor: Bristol-Myers Squibb

Publications and helpful links

General Publications

• Hu Y, Carman JA, Holloway D, Kansal S, Fan L, Goldstine C, Lee D, Somerville JE, Latek R, Townsend R, Johnsen A, Connolly S, Bandyopadhyay S, Shadick N, Weinblatt ME, Furie R, Nadler SG. Development of a Molecular Signature to Monitor Pharmacodynamic Responses Mediated by In Vivo Administration of Glucocorticoids. Arthritis Rheumatol. 2018 Aug;70(8):1331-1342. doi: 10.1002/art.40476. Epub 2018 Jul 12.
• Bandyopadhyay S, Connolly SE, Jabado O, Ye J, Kelly S, Maldonado MA, Westhovens R, Nash P, Merrill JT, Townsend RM. Identification of biomarkers of response to abatacept in patients with SLE using deconvolution of whole blood transcriptomic data from a phase IIb clinical trial. Lupus Sci Med. 2017 Jul 28;4(1):e000206. doi: 10.1136/lupus-2017-000206. eCollection 2017.
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Study record dates

Study Major Dates

• Study Start: September 1, 2005
• Primary Completion (ACTUAL): November 1, 2008
• Study Completion (ACTUAL): November 1, 2008

Study Registration Dates

• First Submitted: June 30, 2005
• First Submitted That Met QC Criteria: July 13, 2005
• First Posted (ESTIMATE): July 14, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): September 22, 2014
• Last Update Submitted That Met QC Criteria: September 11, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: SLE
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Connective Tissue Diseases; Lupus Erythematosus, Systemic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Immune Checkpoint Inhibitors; Prednisone; Abatacept
• Other Study ID Numbers: IM101-042